Seizures

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giddyupp
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40653
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Seizures
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2011-01-13 13:07:06
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Seizures PHPR521
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Seizures
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  1. What is the definition of a seizure?
    Unusual electrical activity in the brain resulting in abnormal movement or behavior.
  2. What is a convulsion?
    paroxysms of involuntary muscular contractions and relaxations
  3. 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
  4. Whar are epilepsy syndromes?
    collections of different seizure types, patterns of onset and family history
  5. What are the seizure pathophysiologies?
    • defective synaptic function triggers seizures
    • neuronal membrane instability
  6. What defective synaptic functions trigger seizures?
    • reduction of inhibition (GABA)
    • enhancement of excitatory activity (glutamate, aspartate, ACh, NE, etc)
  7. 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
  8. What is the definition of epilepsy?
    • chronic disorder of recurrent seizures
    • 2 or more seizures not provoked by other illnesses or circumstances
  9. How are epileptic seizures classified?
    • Where does it start?
    • What type - simple or complex?
  10. What are the characteristics of generalized seizures of epilepsy?
    • no local onset
    • bilateral symmetry (all over both lobes)
  11. How are partial, or focal, seizures characterized?
    start in one lobe and may or may not spread to both lobes
  12. What is a simple seizure?
    no loss of consciousness or alteration of psychic function
  13. What is a complex seizure?
    impaired consciousness
  14. 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
  15. 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
  16. 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
  17. 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
  18. 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
  19. What are the causes of new-onset seizures in adults?
    • stroke
    • head trauma
    • alcohol
    • neurodegenerative disease
    • static encephalopathy
    • brain tumors
    • infection
    • unknown
  20. What events can mimic a seizure?
    • migraine
    • psychogenic or pseudoseizures
    • syncopal disturbances
  21. What sorts of things can cause seizures?
    • Metabolic
    • uremia
    • hypoglycemia
    • hyperglycemia
    • hepatic failure
    • nutritional deficiencies (B6)
    • drug overdose
    • antibiotics (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
  22. 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
  23. What types of imaging can be used to evaluate seizures?
    • MRI (more useful)
    • CT (quick, less expensive)
  24. 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
  25. What are the effects of epilepsy on patients?
    • depression
    • interpersonal relationships
    • employability
    • social functioning (loss of bladder or bowel)
    • QOL (driving, swimming/bathing alone)
  26. 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
  27. What are the effects of poor control of epilepsy?
    • neuronal degeneration
    • new seizure forms
    • increased frequency of seizures
  28. 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
  29. 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
  30. When should combination therapy be tried?
    after 2-3 unsuccessful monotherapies have been tried
  31. 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
  32. How long should drugs be tapered when taking off of antiepileptics?
    3-6 months minimum
  33. What antiepileptics work via GABA?
    • VPA
    • gabapentin
    • vigabatrin
    • BZD
    • barbiturates (phenobarbitol)
    • tiagabine
  34. What antiepileptics work via Na channels?
    • phenytoin
    • lamotrigine
    • CBZ
    • oxcarbazepine
    • topiramate
    • lacosamide
    • zonisamide
  35. What antiepileptics work via Ca channels?
    • VPA
    • ethosuximide
    • zonisamide
  36. What antiepileptics work by unknown/unique methods?
    • felbamate
    • levetiracetam
  37. What are the broad-spectrum antiepileptics?
    • Reasonable choices in most adults, regardless of seizure type:
    • VPA
    • phenobarbital
    • lamotrigine
    • topiramate
    • levetiracetam
    • zonisamide
  38. 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
  39. Which antiepileptics are effective for partial seizures?
    • VPA
    • lamotrigine
    • topiramate
  40. What is the narrowest spectrum antiepileptic and what is it good for?
    ethosuximide - absence seizures
  41. AEDs are the 3rd most common cause of what?
    acute liver failure
  42. Which AED increases ammonia levels?
    VPA
  43. Which AEDs increase hepatic enzyme levels?
    • VPA
    • phenytoin
    • phenobarbital
    • CBZ
  44. Which AEDs cause loss of bone density?
    • Phenytoin
    • CBZ
    • phenobarbital
  45. Which AEDs cause hyponatremia?
    • CBZ
    • oxcarbazepine
  46. Which AEDs should not be used in pts with renal calculi (stone formation)?
    • topiramate
    • zonisamide
  47. Which AEDs are neutral or promote weight loss?
    • lamotrigine
    • topiramate
    • felbamate
    • zonisamide
  48. Which AEDs cause modest weight gain?
    • CBZ
    • gabapentin
    • vigabatrin
  49. Which AEDs cause substantial weight gain?
    • VPA
    • pregabalin
  50. Which AED causes heart block and aggrevates sick sinus syndrome?
    CBZ
  51. Which AEDs prolong T interval?
    • rufinamide
    • lacosamide
  52. Which AED reduces white-cell count?
    CBZ
  53. Which AED causes dose-related thrombocytopenia?
    VPA
  54. Which AED causes gingival hyperplasia?
    phenytoin
  55. 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
  56. Which AEDs are not associated with SJ syndrome and are good alternatives?
    • VPA
    • gabapentin
    • topiramate
    • levetiracetam
  57. Which AED causes target lesions?
    phenobarbital
  58. Which AEDs have adverse cognitive effects?
    • CBZ
    • VPA
    • phenytoin
    • phenobarbital
  59. Which AEDs cause the fewest cognitive effects?
    • gabapentin
    • lamotrigine
  60. Which AED inhibits 2C9 and 2C19?
    VPA
  61. Which AEDs induce P450s?
    • phenytoin
    • phenobarbital
    • CBZ
    • primidone
  62. Which AEDs are greater than 80-90% ppb?
    • phenytoin
    • VPA
  63. Which AEDs have the least chance of DI potential?
    • gabapentin
    • levitiracetam (good for HIV!!!!)
    • zonisamide
    • tiagabine
  64. Which AEDs cause decreased folic acid levels?
    • phenytoin
    • phenobarbital
    • primidone
  65. What is the best reason to obtain AED serum concentrations?
    use as a surrogate marker for adherence
  66. 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
  67. Why is phenobarbital not a first line AED?
    high incidence of cognitive impairment
  68. How can you help avoid skin rashes from lamotrigine?
    • avoid concommittant use of VPA
    • start dose low (<25 mg/d)
    • titrate slowly
  69. What are the first line AEDs for absence seizures?
    • VPA
    • ethosuximide

    avoid CBZ, phenytoin, gabapentin, pregabalin, vigabatrin
  70. What is the first line therapy for myoclonic seizures?
    VPA

    avoid CBZ, phenytoin, gabapentin, lamotrigine, vigabatrin
  71. What are the first line AEDs for tonic-clonic seizures?
    • VPA
    • CBZ
    • oxcarbazepine
    • lamotrigine
  72. What are the first line AEDs for partial seizures?
    • CBZ
    • gabapentin
    • lamotrigine
    • levetiracetam
    • oxcarbazepine
    • topiramate
    • VPA
    • zonisamide
  73. What AED is good for head trauma, neurosurgery, or post-stroke seizures?
    phenytoin
  74. What drug in particular has a role in worsening polycystic ovary syndrome?
    VPA
  75. Which AEDs increase the clearance of OCs?
    • topiramate
    • oxcarbazepine
    • CYP-450 inducers
  76. Which AED has its clearance increased by OCs?
    lamotrigine
  77. What contributes to decreased seizure control in pregnancy?
    • increased drug clearance (esp lamotrigine)
    • hormonal changes
  78. Which AED is the worst drug to use during pregnancy d/t increased risk of birth defects and lowering of IQ scores?
    VPA
  79. What AEDs in particular require administration of supplemental folic acid in women of childbearing age?
    • VPA
    • CBZ
    • phenytoin
    • phenobarbital
    • primidone
  80. What AEDs require additional vitamin K during pregnancy and at birth?
    • phenytoin
    • phenobarbital
    • CBZ
  81. Which AEDs cause fetal hydantoin syndrome?
    • phenytoin
    • CBZ
  82. What should be monitored in a breast feeding infant whose mother is on an AED?
    sedation
  83. 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
  84. 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)
  85. 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)
  86. 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
  87. 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
  88. 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
  89. What is the therapeutic range for CBZ?
    4-12 mcg/mL
  90. What is the therapeutic range for phenobarbital?
    15-45 mcg/mL
  91. What is the therapeutic range for VPA?
    50-100 mcg/mL
  92. Which AEDs are eliminated via the kidney?
    • pregabalin
    • levetiracetam
    • gabapentin
  93. 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
  94. 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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