Clinical Epilepsy

1
Clinical Epilepsy

• American Epilepsy Society

2
Clinical Epilepsy Index
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Definitions and epidemiology Evaluation of a
first seizure Choosing antiepileptic
drugs Drug-drug interactions Adverse
effects Epilepsy comorbidities Discontinuing
antiepileptic drugs Alternative
therapies Epilepsy surgery Status Epilepticus
Non-epileptic events Physiologic Psychogenic Epil
epsy monitoring units Epilepsy
safety SUDEP Pregnancy and epilepsy Pediatric
epilepsy and seizures Appendix for
nurses Appendix for neurologists
3
Definitions
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• ? Seizure the clinical manifestation of an
  abnormal, excessive excitation and
  synchronization of a population of cortical
  neurons
• ? Epilepsy recurrent seizures (two or more)
  which are not provoked by systemic or acute
  neurologic insults

4
Epidemiology of Seizures and Epilepsy
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• ? Seizures
• Incidence 80/100,000 per year
• Lifetime incidence 9 (1/3 febrile convulsions)
• ? Epilepsy
• Incidence 45/100,000 per year
• Point prevalence 0.5-1
• Cumulative lifetime incidence 3

5
ILAE Classification of Seizures
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ILAE International League Against Epilepsy
6
ILAE Classification of Seizures
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7
ILAE Classification of Seizures
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8
Complex Partial Seizures
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• ? Impaired consciousness
• ? Clinical manifestations vary with site of
  origin and degree of spread
• Presence and nature of aura
• Automatisms
• Other motor activity
• ? Duration typically lt 2 minutes

9
Secondarily Generalized Seizures
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• ? Begins focally, with or without focal
  neurological symptoms
• ? Variable symmetry, intensity, and duration of
  tonic (stiffening) and clonic (jerking) phases
• ? Typical duration 1-3 minutes
• ? Postictal confusion, somnolence, with or
  without transient focal deficit

10
EEG Partial Seizure
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• Right Frontal
• seizure

11
EEG Partial Seizure
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• Continuation of
• the same seizure with change in amplitude and
  frequency

12
EEG Partial Seizure
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• Continuation of
• the same seizure
• with spread to the other hemisphere

13
EEG Partial Seizure
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• Continuation of
• the same seizure
• with spread to the other hemisphere

14
ILAE Classification of Seizures
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15
Typical Absence Seizures
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• ? Brief staring spells (petit mal) with
  impairment of awareness
• 3-20 seconds
• Sudden onset and sudden resolution
• Often provoked by hyperventilation
• Onset typically between 4 and 14 years of age
• Often resolve by 18 years of age
• ? Normal development and intelligence
• ? EEG Generalized 3 Hz spike-wave discharges

16
EEG Typical Absence Seizure
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17
Atypical Absence Seizures
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• ? Brief staring spells with variably reduced
  responsiveness
• 5-30 seconds
• Gradual (seconds) onset and resolution
• Generally not provoked by hyperventilation
• Onset typically after 6 years of age
• ? Often in children with global cognitive
  impairment
• ? EEG Generalized slow spike-wave complexes
  (lt2.5 Hz)
• ? Patients often also have Atonic and Tonic
  seizures

18
Atypical Absence Seizures
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19
Myoclonic Seizures
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• Epileptic Myoclonus
• ? Brief, shock-like jerk of a muscle or group of
  muscles
• ? Differentiate from benign, nonepileptic
  myoclonus (e.g., while falling asleep)
• ? EEG Generalized 4-6 Hz polyspike-wave
  discharges

20
Myoclonic Seizures
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21
Tonic and Atonic Seizures
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• Tonic seizures
• Symmetric, tonic muscle contraction of
  extremities with tonic flexion of waist and neck
  
• Duration - 2-20 seconds.
• EEG Sudden attenuation with generalized,
  low-voltage fast activity (most common) or
  generalized polyspike-wave.
• Atonic seizures
• Sudden loss of postural tone
• When severe often results in falls
• When milder produces head nods or jaw drops.
• Consciousness usually impaired
• Duration - usually seconds, rarely more than 1
  minute
• EEG sudden diffuse attenuation or generalized
  polyspike-wave

22
Tonic and Atonic Seizures
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23
Generalized Tonic-Clonic Seizures
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• Associated with loss of consciousness and
  post-ictal confusion/lethargy
• Duration 30-120 seconds
• Tonic phase
• Stiffening and fall
• Often associated with ictal cry
• Clonic Phase
• Rhythmic extremity jerking
• EEG generalized polyspikes

24
Epilepsy Syndromes
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• Epilepsy Syndrome
• Grouping of patients that share similar
• Seizure type(s)
• Age of onset
• Natural history/Prognosis
• EEG patterns
• Genetics
• Response to treatment

25
Epilepsy Syndromes
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26
Etiology of Seizures and Epilepsy
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• ? Infancy and childhood
• Prenatal or birth injury
• Inborn error of metabolism
• Congenital malformation
• ? Childhood and adolescence
• Idiopathic/genetic syndrome
• CNS infection
• Trauma

27
Etiology of Seizures and Epilepsy
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• ? Adolescence and young adult
• Head trauma
• Drug intoxication and withdrawal
• ? Older adult
• Stroke
• Brain tumor
• Acute metabolic disturbances
• Neurodegenerative
• causes of acute symptomatic seizures, not
  epilepsy

28
Questions Raised by a First Seizure
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• Seizure or not?
• Provoked? (ie metabolic precipitant?)
• Seizure type? (focal vs. generalized)
• Evidence of interictal CNS dysfunction?
• Syndrome type?
• Which studies should be obtained?
• Should treatment be started?
• Which drug should be used?

29
Evaluation of a First Seizure
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• History, physical
• Blood tests CBC, electrolytes, glucose, calcium,
  magnesium, phosphate, hepatic and renal function
• Lumbar puncture
• (only if meningitis or encephalitis suspected and
  potential for brain herniation is excluded)
• Blood or urine screen for drugs
• Electroencephalogram (EEG)
• CT or MR brain scan

30
Seizure Precipitants
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• ? Metabolic and Electrolyte Imbalance
• ? Stimulant/other proconvulsant intoxication
• ? Sedative or ethanol withdrawal
• ? Sleep deprivation
• ? Antiepileptic medication reduction or
  inadequate
• AED treatment
• ? Hormonal variations
• ? Stress
• ? Fever or systemic infection
• ? Concussion and/or closed head injury

31
Seizure Precipitants (cont.)
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• Metabolic and Electrolyte Imbalance
• Low blood glucose
• (or high glucose, esp. w/ hyperosmolar state)
• Low sodium
• Low calcium
• Low magnesium

32
Metabolic abnormalities and seizures
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BS blood sugar.
33
Seizure Precipitants (cont.)
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• Stimulants/Other Pro-convulsant Intoxication
• ? IV drug use
• ? Cocaine
• ? Ephedrine
• ? Other herbal remedies
• ? Medication reduction

34
Return to index
Seizure Precipitants (cont.)

• Medications that can lower seizure threshold
• Antidepressants
• Bupropion
• Tricyclics
• Neuroleptics
• Phenothiazines
• Clozapine
• Theophylline
• Isoniazid
• Penicillins
• Cyclosporin
• Meperidine

35
EEG Abnormalities
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• ? Background abnormalities significant
  asymmetries and/or degree of slowing
  inappropriate for clinical state or age
• ? Interictal abnormalities associated with
  seizures and epilepsy
• Spikes
• Sharp waves
• Spike-wave complexes
• ? May be focal, lateralized, generalized

36
EEG Abnormalities
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Interictal left temporal sharp wave consistent
with a diagnosis of partial epilepsy of left
temporal origin
37
EEG Abnormalities
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Interictal generalized polyspike-wave complex
consistent with a diaganosis of idiopathic
generalized epilepsy
38
Medical Treatment of First Seizure
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• Whether to treat first seizure is controversial
• 16-62 of unprovoked seizures will recur within 5
  years
• Relapse rate may be reduced by antiepileptic
  drugs
• Relapse rate increased if
• abnormal imaging
• abnormal neurological exam
• abnormal EEG
• family history
• ? Quality of life issues are important (ie
  driving)

First Seizure Trial Group. Neurology.
199343478483. PubMed Camfield et al.
Epilepsia. 200243662663. PubMed
39
Choosing Antiepileptic Drugs
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• Considerations
• Seizure type
• Epilepsy syndrome
• Efficacy
• Cost
• Pharmacokinetic profile
• Adverse effects
• Patients related medical conditions
• (ie beneficial or deleterious effects on
  co-morbid conditions)

40
Choosing Antiepileptic Drugs
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• Limited placebo-controlled trials available,
  particularly of newer AEDs
• Several drugs are commonly used for indications
  other than those for which they are officially
  approved/recommended
• Choice of AED for partial epilepsy depends
  largely on drug side-effect profile and patients
  preference/concerns
• Choice of AED for generalized epilepsy depends on
  predominant seizure type(s) as well as drug
  side-effect profile and patients
  preference/concerns
• See appendix for
• ILAE Summary Guidelines and Summary of AAN
  evidence-based guidelines

41
Choosing Antiepileptic Drugs
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• Broad-Spectrum Agents
• Valproate
• Felbamate
• Lamotrigine
• Topiramate
• Zonisamide
• Levetiracetam
• Rufinamide
• Vigabatrin

• Narrow-Spectrum Agents
• Partial onset seizures
• Phenytoin
• Carbamazepine
• Oxcarbazepine
• Gabapentin
• Pregabalin
• Tiagabine
• Lacosamide
• Absence
• Ethosuximide

New AEDs (approved 2008) categorization may
change
42
Choosing Antiepileptic Drugs (cont.)
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• Monotherapy for Partial Seizures
• Best evidence and FDA indication
• Carbamazepine, Oxcarbazepine, Phenytoin,
  Topiramate
• Similar efficacy, likely better tolerated
• Lamotrigine, Gabapentin, Levetiracetam
• Also shown to be effective
• Valproate, Phenobarbital, Felbamate, Lacosamide
• Limited data but commonly used
• Zonisamide, Pregabalin
• Azar NJ and BW Abou-Khalil. Seminars in
  Neurology. 2008 28(3) 305-316. PubMed

43
Choosing Antiepileptic Drugs (cont.)
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• Monotherapy for Generalized-Onset Tonic-Clonic
  Seizures
• Best evidence and FDA Indication
• Valproate, Topiramate
• Also shown to be effective
• Zonisamide, Levetiracetam
• Phenytoin, Carbamazepine (may exacerbate absence
  and myoclonic sz )
• Lamotrigine (may exacerbate myoclonic sz of
  symptomatic generalized epilepsies)

44
Choosing Antiepileptic Drugs (cont.)
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• Absence seizures
• Best evidence
• Ethosuximide (limited spectrum, absence only)
• Valproate
• Also shown to be effective
• Lamotrigine
• May be considered as second-line
• Zonisamide, Levetiracetam, Topiramate, Felbamate,
  Clonazepam

45
Choosing Antiepileptic Drugs (cont.)
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• Myoclonic Seizures
• Best evidence
• Valproate
• Levetiracetam (FDA indication as adjunctive tx)
• Clonazepam (FDA indication)
• Possibly effective
• Zonisamide, Topiramate

46
Choosing Antiepileptic Drugs (cont.)
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• Lennox-Gastaut Syndrome
• Best evidence/FDA indication
• Topiramate, Felbamate, Clonazepam, Lamotrigine,
  Rufinamide, Valproate
• FDA approval is for adjunctive treatment for
  all except clonazepam
• Some evidence of efficacy
• Zonisamide, Levetiracetam

47
Antiepileptic Drug Monotherapy
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• ? Simplifies treatment
• ? Reduces adverse effects
• ? Conversion to monotherapy
• Eliminate sedative drugs first
• Withdraw antiepileptic drugs slowly over several
  months

48
Antiepileptic Drug Interactions
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• AEDs that may induce metabolism of other drugs
• carbamazepine, phenytoin, phenobarbital,
  primidone
• AEDs that inhibit metabolism of other drugs
• valproate, felbamate
• AEDs that are highly protein bound
• valproate, phenytoin, tiagabine
• carbamazepine, oxcarbazepine
• topiramate is moderately protein bound
• Other drugs may alter metabolism or protein
  binding of antiepileptic drugs (especially
  antibiotics, chemotherapeutic agents and
  antidepressants)

49
AEDs and INR
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AEDs increase metabolism of warfarin, but
warfarin is 99 protein bound, and PHT and VPA
increase warfarins free fraction. INR
international normalized ratio. Boggs J. In
Ettinger AB, Devinsky O, eds. Managing Epilepsy
and Co-Existing Disorders. Boston
Butterworth-Heinemann 200239-47.
50
Antiepileptic Drug Interactions
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• Drugs that may decrease the efficacy of
• oral contraceptive pills
• Phenytoin
• Carbamazepine
• Phenobarbital
• Topiramate
• Oxcarbazepine
• Felbamate
• at high doses
• High-dose birth control pills are recommended
  for patients taking these medications.

51
Antiepileptic Drug Interactions
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• Lamotrigine and hormonal contraception
• Oral contraceptive pills can decrease lamotrigine
  levels by 50
• Lamotrigine levels will increase significantly
  during the placebo week, possibly leading to
  toxicity
• Lamotrigine can decrease progesterone levels.
  Patients using Depo-provera may need shorter
  intervals between injections.

52
AED Serum Concentrations
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• AED serum concentrations are to be used as a
  guide, not dictate clinical decision making.
• Serum concentrations are useful when optimizing
  AED therapy, assessing compliance, monitoring
  during pregnancy or oral contraceptive use, or
  teasing out drug-drug interactions.
• Individual patients define their own
  therapeutic and toxic ranges.

Table Summary of ILAE guidelines on therapeutic
drug levels
Patsalos et al. Epilepsia. 20084912391276.
PubMed
53
Adverse Effects of AEDs Common
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• Typically dose-related
• Dizziness , Fatigue , Ataxia, Diplopia
• all AEDs
• Irritability
• levetiracetam
• Word-finding difficulty
• topiramate
• Weight loss/anorexia
• topiramate, zonisamide, felbamate
• Weight gain
• valproate (also associated with polycystic
  ovarian syndrome )
• carbamazepine, gabapentin, pregabalin

54
Adverse Effects of AEDs Serious
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• Typically Idiosyncratic
• Renal stones
• topiramate, zonisamide
• Anhydrosis, heat stroke
• topiramate
• Acute closed-angle glaucoma
• topiramate
• Hyponatremia
• carbamazepine, oxcarbazepine

55
Adverse Effects of AEDs Serious
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• Typically Idiosyncratic
• Aplastic anemia
• felbamate, zonisamide, valproate, carbamazepine
• Hepatic Failure
• valproate, felbamate, lamotrigine, phenobarbital
• Peripheral vision loss
• vigabatrin
• Rash
• phenytoin, lamotrigine, zonisamide, carbamazepine

56
Adverse Effects of AEDs Rash
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• 15.9 patients experienced a rash attributed to
  an AED
• Average rate of AED-related rash for a given AED
  2.8, 2.1 causing AED discontinuation.
• Predictors significant in multivariate analysis
• occurrence of another AED-rash

Arif H. et al. Neurology. 20076817011709.
PubMed
57
Adverse Effects of AEDs Rash
Return to index

• Stevens-Johnson Syndrome (SJS) and
• Toxic Epidermal Necrolysis (TENS)
• severe life threatening allergic reaction
• blisters and erosions of the skin, particularly
  palms/soles and mucous membranes
• fever and malaise
• rare severe risk roughly 1-10/10,000 for many
  AEDs
• rapid titration of lamotrigine especially in
  combination with valproate increases risk

58
AED-related rash in adult patients with epilepsy
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• ?? rash rate significantly greater than average
  of all other AEDs (plt0.003)
• ?? rash rate significantly lower than average of
  all other AEDs (plt0.003)
• ? trend towards significantly higher than
  average rash rate of all other AEDs
  (0.003ltplt0.05)
• ? trend towards significantly lower than average
  rash rate of all other AEDs (0.003ltplt0.05)

Arif H. et al. Neurology. 20076817011709.
PubMed
59
Adverse Effects of AEDs Rash
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• Drugs rarely associated with rash
• Valproate
• Gabapentin
• Pregabalin
• Levetiracetam
• Topiramate

60
AED-related rash in Asian patients
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FDA alert 12/2007 Risk of dangerous or even
fatal skin reactions such as Steven-Johnson
Syndrome and Toxic epidermal necrolysis is
incrased in patients with HLA-B1502 allele
Estimated absolute risk for those with the
allele 5 This allele is almost exclusively
found in Asians 10-15 of population in China,
Thailand, Malaysia, Indonesia, Phillipines and
Taiwan 2-4 in India lt1 in Japan and
Korea 59/60 Asian patients w/ SJS/TEN had this
allele vs 4 of CBZ tolerant patients Asians
should be screened for the HLA-B1502 allele
before starting treatment with carbamazepine The
se patients may also be at risk with other AEDs
(phenytoin)
www.fda.gov
61
Epilepsy Comorbidities and AEDs
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• Osteoporosis
• Mostly worsened by the enzyme inducers
  phenytoin, phenobarbital, primidone.
  Carbamazepine data equivocal.
• Equivocal data with valproate, unavailable for
  other non- inducers.
• Patients should take calcium 1000-1500/day Vit D
  400-4000/day
• Pack AM Neurology. 20087015861593.
  PubMed
• Migraine
• Consider topiramate, valproate
• Depression
• Can be exacerbated by levetiracetam (and less so
  zonisamide)
• Can be helped by lamotrigine and possibly
  gabapentin, pregabalin (and vagus nerve
  stimulator)

62
Depression in Epilepsy
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• Prodromal, peri-ictal, interictal
• 20 to 60 in many series
• Suicide rate 5 times higher than that of general
  population

Ettinger AB, et al. J Epilepsy.
19981120-24. Barraclough BM. The suicide rate
of epilepsy. Acta Psychiatr Scand. 1987
Oct76(4)339345. PubMed
63
Return to index
Depression in Epilepsy
Score Cutpoints Major Depression gt 21 Mod/mild
Depression 15-21 No Depression lt 15
CES-D. overall group effect (p 0.001),
comparison between epilepsy and asthma groups (p
0.05).
Ettinger A, Reed M, Cramer J. Neurology.
20046310081014. PubMed
64
Return to index
Bipolar Depression in Epilepsy
Bipolar symptoms in epilepsy and other chronic
conditions
Ettinger AB et al. Neurology. 200565535540.
PubMed
65
Possible suicide risk with AEDs
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• Recent FDA alert (1/2008)
• Meta-analysis of 199 placebo-controlled add-on tx
  trials
• (44,000 patients)
• Suicidality with adjunct AEDs than adjunct
  placebo
• 0.43 vs 0.22
• Extra 2.1 patients per 1000 more patients will
  have suicidality
• 4 suicides with AEDs vs 0 with placebo
• generally consistent across the 11 AEDs
• Data analysis is controversial and overall
  difference is very small
• Further investigation is needed
• Clinicians should be aware of potential risk and
  screen for
• depression/suicidality

www.fda.gov
66
Starting AEDs
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• Discuss likely adverse effects
• Discuss unlikely but important adverse effects
• Discuss likelihood of success
• Discuss recording/reporting seizures, adverse
  effects, potential precipitants

67
Discontinuing AEDs
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• ? Seizure freedom for ? 2 yearsimplies overall
  gt60 chance of successful withdrawal in some
  epilepsy syndromes
• ? Favorable factors
• Control achieved easily on one drug at low dose
• No previous unsuccessful attempts at withdrawal
• Normal neurologic exam and EEG
• Primary generalized seizures except JME
• Benign syndrome
• ? Consider relative risks/benefits (e.g.,
  driving, pregnancy)
• Practice parameter. Neurology. 199647600602.
  PubMed

68
Evaluation After Seizure Recurrence
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• ? Progressive pathology?
• ? Avoidable precipitant?
• ? If on AED
• Problem with compliance?
• Pharmacokinetic factor?
• Increase dose?
• Change medication?
• ? If not on AED
• Start therapy?

69
Non-Drug Treatment/Lifestyle Modifications
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• ? Adequate sleep
• ? Avoidance of alcohol, stimulants, etc.
• ? Avoidance of known precipitants
• ? Stress reduction specific techniques

70
Ketogenic Diet
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• Main experience with children, especially with
  multiple seizure types
• Likely anti-seizure effect of ketosis (beta
  hydroxybutyrate), but other mechanisms also may
  be responsible for beneficial effects
• Low carbohydrate, adequate protein, high fat
• 50 with a gt50 seizure reduction
• 30 with gt90 reduction
• Side effects include kidney stones, weight loss,
  acidosis, dyslipidemia

71
Alternative Diets
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• ? Modified Atkins diet
• 10 g/day carbohydrates to start, fats encouraged
• No protein, calorie, fluid restriction
• 3 reports to date from Johns Hopkins, 1 from
  South Korea
• 47 all children with gt50 seizure reduction
• Studies underway for adults
• ? Low-glycemic index treatment
• 40-60 g/day low-glycemic carbohydrates
• Portions generally controlled
• Single report from Massachusetts General

72
Patient Selection for Surgery
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• ? Epilepsy syndrome not responsive to medical
  management
• Unacceptable seizure control despite maximum
  tolerated doses of 2-3 appropriate drugs as
  monotherapy
• ? Epilepsy syndrome amenable to surgical
  treatment

73
Evaluation for Surgery
Return to index

• History and Exam consistency, localization of
  seizure onset and progression
• MRI 1.5 mm coronal cuts with sequences
  sensitive to gray-white differentiation and to
  gliosis
• Other neuroimaging options PET, ictal SPECT
• EEG ictal and interictal, special electrodes
• Magnetoencephalography (MEG) interictal,
  mapping
• Neuropsychological battery
• Psychosocial evaluation
• Intracarotid amobarbital test (Wada)

74
Surgical Treatment
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• ? Potentially curative
• Resection of epileptogenic region (focus)
  avoiding significant new neurologic deficit
• ? Palliative
• Partial resection of epileptogenic region
• Disconnection procedure to prevent seizure spread
  
• Callosotomy
• Multiple subpial transections

75
Epilepsy Surgery Outcomes
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Engel J, Jr, et al. Neurology. 200360538547.
PubMed
76
Epilepsy Surgery
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• Corpus Callosotomy
• Palliative surgery for intractable epilepsies
  with drop attacks
• (i.e. Lennox-Gastaut Syndrome)
• Up to 75 have gt 75 reduction in atonic seizures
  
• Risk of disconnection syndromes
• Hemispherectomy
• Indicated for catastrophic hemispheric
  epilepsies, usually presenting in children (i.e.
  Rasmussens encepalitis, hemimegalencephaly)
• 43-79 seizure free (varies by etiology)
• Functional hemispherectomy (disconnection
  without removal) now more commonly performed
• Multiple Subpial Transections
• Cuts horizontal cortical-cortical connections
• Generally reserved for epileptogenic regions in
  functional cortex

Spencer SS and L Huh. Lancet Neurol. (2008),
525537. Pubmed
77
Vagus Nerve Stimulator
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• ? Intermittent programmed electrical
  stimulation of left vagus nerve
• ? Option of magnet activated stimulation
• ? Adverse effects local, related to stimulus
• (hoarseness, throat discomfort, dyspnea)
• ? Mechanism unknown
• ? Clinical trials show that 35 of patients
  have a 50 reduction in seizure frequency and 20
  experience a 75 reduction after 18 months of
  therapy.
• ? May improve mood and allow AED reduction
• ? FDA approved for refractory partial onset
  seizures and refractory depression

78
Status Epilepticus
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• ? Definition
• More than 10 minutes of continuous seizure
  activity
• or
• Two or more sequential seizures without full
  recovery between seizures

79
Status Epilepticus (SE)
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• ? A medical emergency
• Adverse consequences can include hypoxia,
  hypotension, acidosis, hyperthermia,
  rhabdomyolysis and neuronal injury
• Know the recommended sequential protocol for
  treatment and distribute a written protocol to
  emergency rooms, ICUs and housestaff.
• Goal stop seizures as soon as possible

80
SE Treatment Algorithm
Return to index

• One commonly used treatment algorithm is
• First 5 minutes
• Check emergency ABCs
• Give O2
• Obtain IV access
• Begin EKG monitoring
• Check fingerstick glucose
• Draw blood for Chem-7, Magnesium, Calcium,
  Phosphate, CBC, LFTs, AED levels, ABG, troponin
• Toxicology screen (urine and blood).

Arif H, Hirsch LJ. Semin Neurol. 200828342354.
PubMed
81
Return to index
SE Treatment Algorithm

• 6-10 minutes
• Thiamine 100 mg IV 50 ml of D50 IV unless
  adequate glucose known.
• Lorazepam 4 mg IV over 2 mins if still seizing,
  repeat X 1 in 5 mins.
• If no rapid IV access give diazepam 20 mg PR or
  midazolam 10 mg intranasally, buccally or IM.

Arif H, Hirsch LJ. Semin Neurol. 200828342354.
PubMed
82
Return to index
SE Treatment Algorithm

• 10-20 minutes
• If seizures persist, begin fosphenytoin 20 mg/kg
  IV at 150 mg/min, with blood pressure and EKG
  monitoring.
• Reasonable to bypass this step, or perform
  subsequent step simultaneous with fosphenytoin
  loading

Arif H, Hirsch LJ. Semin Neurol. 200828342354.
PubMed
83
Return to index
SE Treatment Algorithm

• 10-60 minutes one (or more) of the following 4
  options
• (intubation usually necessary except for
  valproate)
• Continuous IV midazolam Load 0.2 mg/kg repeat
  0.2-0.4 mg/kg boluses every 5 minutes until
  seizures stop, up to a maximum total loading dose
  of 2 mg/kg. Initial rate 0.1 mg/kg/hr. cIV
  dose range 0.05 2.9 mg/kg/hr.
• OR
• Continuous IV propofol Load 1 mg/kg repeat
  1-2 mg/kg boluses every 3-5 minutes until
  seizures stop, up to maximum total loading dose
  of 10 mg/kg. Initial cIV rate 2 mg/kg/h. cIV
  dose range 1-15 mg/kg/hr. Avoid gt48 hrs of gt5
  mg/kg/h (increased risk of propofol infusion
  syndrome).
• OR
• IV valproate 40 mg/kg over 10 minutes. If
  still seizing, additional 20 mg/kg over 5
  minutes.
• OR
• IV phenobarbital 20 mg/kg IV at 50-100 mg/min.

Arif H, Hirsch LJ. Semin Neurol. 200828342354.
PubMed
84
Return to index
SE Treatment Algorithm
Arif H, Hirsch LJ. Semin Neurol. 200828342354.
PubMed

• 60 minutes
• Continous IV Pentobarbital. Load 5 mg/kg at up
  to 50 mg/min repeat 5 mg/kg boluses until
  seizures stop. Initial cIV rate 1 mg/kg/hr.
  cIV-dose range 0.5-10 mg/kg/hr traditionally
  titrated to suppression-burst on EEG.
• Begin EEG monitoring ASAP if patient does not
• rapidly awaken, or if any CIV treatment is used.
• 20 of those patients successfully treated
  clinical for status will still be seizing on EEG.
  
• Treiman et al. N Engl J Med. 19983397928.
  PubMed

85
Differential Diagnosis of Non-epileptic Events
Physiologic
Return to index

• Syncope
• Cardiac (Arrhythmia)
• Non-Cardiac Syncope (Vasovagal, Dysautonomic)
• Metabolic (Hypoglycemia)
• Migraine
• Sleep Disorders (Narcolepsy)
• Movement Disorders (Paroxysmal Dyskinesia)
• Transient Ischemic Attacks

86
Differential Diagnosis of Non-epileptic Events
Psychogenic
Return to index

• Psychogenic Seizures
• Malingering
• Panic Attacks
• Intermittent Explosive Disorder
• Breath-holding Spells

87
Syncope
Return to index

• ? Characteristic warning, usually gradual
  (except with cardiac arrhythmia)
• ? Typical precipitants (except with cardiac
  arrhythmia)
• ? Minimal to no postictal confusion/somnolence
• ? Convulsive syncope tonicgtclonic
  manifestations, usually lt 30 sec usually from
  disinhibited brainstem structures (only rarely
  from cortical hypersynchronous activity)

88
Syncope vs Seizure Before Spell
Return to index
Hirsch et al, Merritts Textbook of Neurology,
2007
89
Syncope vs Seizure During Spell
Return to index
Hirsch et al, Merritts Textbook of Neurology,
2007
90
Syncope vs Seizure During Spell
Return to index
Hirsch et al, Merritts Textbook of Neurology,
2007
91
Syncope vs Seizure During Spell
Return to index
Hirsch et al, Merritts Textbook of Neurology,
2007
92
Syncope vs Seizure After spell
Return to index
Hirsch et al, Merritts Textbook of Neurology,
2007
93
Features That Are Not Helpful in Differentiating
Syncope from Seizure
Return to index

• Incontinence
• Prolactin level
• Dizziness
• Fear

• Injury other than lateral tongue biting
• Eye movements (rolling back)
• Brief automatisms

Hirsch et al, Merritts Textbook of Neurology,
2007
94
Return to index
Migraine aura vs. occipital seizure
Hirsch et al, Merritts Textbook of Neurology,
2007
95
Psychogenic Non-epileptic Seizures
Return to index

• 10-45 of patients referred for intractable
  spells
• Females gt males
• Psychiatric mechanism dissociation, conversion
• Common association with physical, emotional, or
  sexual abuse
• Spells with non-epileptic etiology
• No obvious ictal eeg correlation
• (classically normal awake background during
  episode of impaired consciousness)
• Caveats Diagnosis can be complicated
• The majority of simple partial seizures have no
  EEG correlation
• Frontal lobe seizures may have unusual
  semiology and no discernable EEG correlation

96
Psychogenic Non-epileptic Seizures
Return to index

• FEATURES SUGGESTIVE OF NONEPILEPTIC PSYCHOGENIC
  SEIZURES
• Eye Closure
• Pelvic thrusting
• Opisthotonus
• Side-to-side head shaking
• Prolonged duration (gt4 minutes)
• Stopping and starting
• Suggestibility

97
Psychogenic Non-epileptic Seizures
98
Psychogenic Non-epileptic Seizures
Return to index

• ? Represents psychiatric disease
• ? Once recognized, approximately 50 respond
  well to specific psychiatric treatment
• ? Epileptic and nonepileptic seizures may
  co-exist
• ? Video-EEG monitoring often required for
  diagnosis

99
Utility of epilepsy video/EEG monitoring units
Return to index

• Epilepsy Monitoring Unit (EMU)
• Inpatient unit with specialized personnel
• Continuous video and EEG recording
• Utility
• Differentiate between epileptic and non-epileptic
  spells
• Identification of unrecognized seizures
• Recording seizures for presurgical evaluation
• NAEC Guidelines for EMU evaluation
• Treatment failure of 1 year
• Failure of 2-3 AEDs

100
Utility of epilepsy video/EEG monitoring
unitsNon-epileptic spells
Return to index

• Study of 213 EMU admissions
• 21 had purely nonepileptic events
• Treated as if epilepsy for a mean of 9 yrs
• Half treated w/ gt3 AEDs
• EMU yielded definitive diagnosis in 88

Smolowitz et al. American Journal of Medical
Quality. 200722(2)117122. PubMed
101
Utility of epilepsy video/EEG monitoring units
(EMU) Epilepsy
Return to index

• Early Identification of Refractory Epilepsy n525
• Kwan P and MJ Brodie. N Engl J Med. 342 (2000),
  314-9. Pubmed
• 192 (37) patients were refractory.
• Only 11 of patients became seizure-free if the
  first drug was ineffective.
• Suggests need for early pre-surgical evaluation
• Patient awareness of seizures n31
• Blum DE et al. Neurology. 1996472604. PubMed
• 30 patients deny all seizures
• Only 23 were aware of all seizures

102
Sudden Unexplained Death in Epilepsy SUDEP
Return to index

• Definition
• sudden, unexpected, witnessed or unwitnessed,
  nontraumatic and non-drowning death in a patient
  with epilepsy where the postmortem examination
  does not reveal a toxicologic or anatomic cause
  of death, with or without evidence of a seizure
  and excluding documented status epilepticus.

Nashef L, Brown S. Lancet. 1996348(9038)1324132
5. PubMed
103
Sudden Unexplained Death in Epilepsy SUDEP
Return to index

• Witnessed SUDEP Langan Y et al. JNNP
  200068211213. PubMed
• 15/135 SUDEP cases were witnessed.
• 12/15 were associated with a convulsive seizure.
• One collapse occurred 5 minutes after a GTC
  seizure and one after an aura.
• One patient died in a probable postictal state.
• 12/15 were noted to have experienced respiratory
  difficulties.
• Suggests that respiratory dysfunction may be an
  important contributing factor in SUDEP.
• Suggests that positioning or stimulation of
  respiration may be important in the prevention of
  SUDEP.

104
Epidemiology of SUDEP
Return to index

• SUDEP
• Represents about 2-18 of deaths among the
  general population of patients with epilepsy.
• Risk of sudden death in epilepsy patients 24 X
  that of general population.
• Mean SUDEP incidence 3.7/1000 people per year.
• Higher in patients referred for epilepsy surgery
  (up to 1 per 100 per year).

Walczak TS et al. Neurology. 20015651925.
PubMed
105
Epidemiology of SUDEP
Return to index

• SUDEP Risk Factors
• History of and number of GTCS
• Frequent seizures
• Subtherapeutic AED levels
• Young adults
• Long epilepsy duration early epilepsy onset
• AED polytherapy
• Frequent AED changes
• IQ lt70

Tomson et al. Epilepsia. 200546(Suppl 11)5461.
PubMed
106
Recommendations for SUDEP prevention
Return to index

• Optimize seizure control as promptly as possible
• Re-evaluate epilepsy diagnosis and treatment as
  soon as 2 AEDs have failed, or when GTC szs are
  frequent despite initial AED treatment
• Consider epilepsy surgery at that point
• Maximize compliance with AEDs
• Use the least number of AEDs needed to control
  seizures
• Add AED with the aim of replacing the current AED
  in a timely fashion (But not at the expense of
  worsening of seizure control)
• Educate patients and families

107
Driving and Epilepsy
Return to index

• ? Regulation varies state by state regarding
• Reporting requirements
• Required seizure-free period
• Favorable/unfavorable modifiers
• ? Insurance issues
• ? Employment issues
• Resource www.efa.org

108
First AidTonic-Clonic Seizure
Return to index

• ? After seizure ends, turn person on side with
  face turned toward ground to keep airway clear,
  protect from nearby hazards
• ? Transfer to hospital needed for
• Multiple seizures or status epilepticus
• Person is pregnant, injured, diabetic
• New onset seizures
• ? DO NOT put any object in mouth or restrain

109
Pregnancy and EpilepsyMajor Congenital
Malformation and AEDs
Return to index

• Most available data on risk of AEDs comes from
  pregnancy registries.
• Main outcome variable of most registries are
  major congenital malformations (MCM)
• MCM malformation that affects physiologic
  function or requires surgery
• Neural tube defects
• Cardiac defects
• Genitourinary defects
• Oral clefts
• MCMs are more common with AED exposure
• MCM risk in general population 1.6-2.1
• MCM risk with AED monotherapy 4.5 (OR 2.6)
• MCM risk with Polytherapy 8.6 (OR 5.1)

Holmes et al. N Engl J Med. 200134411321138.
PubMed
110
Pregnancy and Epilepsy
Return to index

• 96 of pregnancies in mothers with epilepsy
  produce normal children
• Spontaneous abortions and pre-term birth are more
  common in women with epilepsy
• There is an increased rate of fetal malformations
  associated with antiepileptic drug exposure
• Seizures during pregnancy may be harmful
• Tonic-clonic seizures associated with
  intracranial hemorrhage, fetal bradycardia and
  lower IQ in children
• Status associated with increased fetal and
  maternal mortality in some studies
• Insufficient data on non-convulsive seizures

Harden CL et al. Neurology. 2009 Jul
1473(2)133-41. PubMed
111
Pregnancy and EpilepsyMajor Congenital
Malformation and AEDs
Return to index

• Valproate consistently associated with poorer
  outcomes
• MCM rate with valproate monotherapy 6.2-13.2
  across 5 registries
• Most studies show dose- related increase in risk
  with doses gt 1000mg/day
• Polytherapy regimens including valproate also
  substantially increased risk of MCM
• Valproate associated with lower IQs in exposed
  children
• Phenobarbital probably also poses higher risk of
  MCM
• compared with other monotherapy regimens.

Meador KJ, Pennell PB, Harden CL, Gordon JC,
Tomson T, Kaplan PW, Holmes GL, French JA, Hauser
WA, Wells PG, Cramer JA., HOPE Work Group.
Pregnancy registries in epilepsy A consensus
statement on health outcomes. Neurology.
20087111091117. PubMed
112
Pregnancy and EpilepsyMajor Congenital
Malformation and AEDs
Return to index

• MCM rate similar among other studied AEDs in
  monotherapy, but not enough data to show
  significant difference between them
• Levetiracetam
• Early data promising (0 in monotherapy, 2.7 in
  polytx)
• Carbamazepine (2.2-3.9)
• Substantial data available, relatively good track
  record
• Lamotrigine (1.4-4.4)
• Increased risk (5.4) with doses gt 400/day
• Gabapentin (0-3.2)
• Topiramate (0-4.8)
• Phenytoin (3.2-6.7)
• Zonisamide, Pregabalin
• Limited monotherapy data

Meador KJ, Pennell PB, Harden CL, Gordon JC,
Tomson T, Kaplan PW, Holmes GL, French JA, Hauser
WA, Wells PG, Cramer JA., HOPE Work Group.
Pregnancy registries in epilepsy A consensus
statement on health outcomes. Neurology.
20087111091117. PubMed
113
Pregnancy and Epilepsy Guidelines for Management
Return to index

• All women of child-bearing potential should
  receive education and carefully considered
  management before and during pregnancy to
  optimize the chances of a good outcome for both
  mother and child.

Reference Liporace J, DAbreu. Epilepsy and
Womens Health Family Planning, Bone Health,
Menopause, and Menstrual Related Seizures. Mayo
Clinic Proceedings 2003 78 497-506.
114
Pregnancy and Epilepsy Major Congenital
Malformation Rates in Monotherapy
Return to index
Gerard E. and Pack AM Curr Neurol Neurosci Rep.
2008 Jul8(4)325-32.PubMed
115
Pregnancy and Epilepsy Guidelines for Management
Return to index

• Education
• Most women with epilepsy have normal children
• Risk of fetal malformations is increased with AED
  exposure
• AED teratogenicity is related to exposure in the
  first trimester of pregnancy
• Planning should begin well before pregnancy
• Seizures may be deleterious to the fetus
• Compliance with AED treatment is important
• Prenatal diagnosis of fetal malformations is
  possible

116
Pregnancy and Epilepsy Guidelines for Management
Return to index

• Before pregnancy
• Attempt AED monotherapy with lowest effective
  dose
• Consider switching AEDs prior to pregnancy,
  particularly if on valproate
• Establish baseline therapeutic levels
• Folate supplementation
• 0.4 5 mg/day

117
Pregnancy and Epilepsy Guidelines for Management
Return to index

• During pregnancy
• Monitor AED dose requirements to maximize seizure
  control
• Particularly with lamotrigine (levels fall gt 50
  and sz increase)
• Also increased clearance of levetiracetam,
  oxcarbazepine, phenobarbital and phenytoin
• Continue folate supplementation
• High-risk OB care, consider prenatal diagnosis of
  malformations, level II ultrasound
• Consider Vit K (10 mg/day orally) starting at 36
  weeks

118
Breast Feeding and Epilepsy
Return to index

• Breastfeeding should be encouraged unless clear
  risk posed
• Probably safe
• Carbamazepine
• Phenytoin
• Valproate
• Lamotrigine
• Use with caution in lactating women
• Primidone
• Phenobarbital
• Ethosuximide

Pennell et al. Epilepsy and Behavior. 2007. 11
263-9 crossref
119
Neonatal Seizures
Return to index

• ? Incidence 1.6 3.5 per 1000 live births
• ? Major risk factors are prematurity, low-birth
  weight, hypoxic-ischemic encephalopathy
• ? Associated with increased morbidity and
  mortality
• ? May be symptomatic of treatable, serious
  condition (hypoglycemia, meningitis)
• ? Diagnosis observation with vs. without EEG

Lanska MJ et al. Neurology. 1995
Apr45(4)724732. PubMed Saliba RM et al. Am J
Epidemiol. 1999150763769. PubMed
120
Recognition of Neonatal Seizures
Return to index

• ? Observation of abnormal, repetitive attacks of
  movements, postures or behaviors
• ? Classification
• subtle
• tonic
• clonic
• myoclonic
• autonomic
• ? Evaluation for cause(s) of seizures
• ? Confirmation/support by EEG

121
Examples of Acquired Conditions That May Provoke
Neonatal Seizures
Return to index

• ? Hypoxia-ischemia
• ? Physical trauma
• ? Toxic-metabolic
• ? Inborn errors of metabolism
• ? Systemic or CNS infections
• ? Intracranial hemorrhage

122
Acute Treatment of Neonatal Seizures
Return to index

• ? Phenobarbital loading dose 20 mg/kg
• ? Fosphenytoin
• loading dose 20 mg/kg
• ? Diazepam first dose about 0.25 mg/kg
• ? Lorazepam first dose about 0.05 to 0.1 mg/kg

123
Selected Pediatric Epilepsy Syndromes
Return to index

• ? Epileptic Encephalopathies
• West Syndrome infantile onset, hypsarrhythmic
  EEG infantile spasms cryptogenic vs.
  symptomatic
• Lennox-Gastaut Syndrome childhood onset, slow
  spike-wave EEG, tonic, atypical absence, atonic
  and other seizure types, and mental retardation
• Myoclonic epilepsies of infancy and early
  childhood heterogeneous

124
Return to index
Selected Pediatric Epilepsy Syndromes

• Febrile seizures
• Occur between 6 months and 5 years of age
• Simple Duration less than 15 minutes,
  generalized, and do not recur within 24 hours
• Complex Duration longer than 15 minutes, focal
  in nature or recur within 24 hours
• Risk Factors for development of epilepsy
• Complex febrile seizures
• Neurodevelopmental abnormalities
• Afebrile seizures in first-degree relatives
• Recurrent febrile seizures
• Febrile seizures following brief and low grade
  fever
• Febrile seizure onset in first year

125
Return to index
Selected Pediatric Epilepsy Syndromes

• Benign epilepsy with centrotemporal spikes
• Nocturnal simple partial seizures
• With or without secondary generalization
• Childhood epilepsy with occipital paroxysms
• Visual or autonomic phenomena, with ictal
  vomiting and eye movements
• With or without secondary generalization

126
Return to index
Selected Pediatric Epilepsy Syndromes

• ? Idiopathic generalized epilepsies
• Childhood absence epilepsy
• Absence seizures
• With or without tonic-clonic seizures
• Juvenile myoclonic epilepsy
• Myoclonic jerks
• Rare tonic-clonic seizures
• With or without absence seizues

127
AEDs in Pediatrics
Return to index

• ? Extrapolation of efficacy data from adult
  studies
• ? Importance of adverse effects relative to
  efficacy
• ? Susceptibility to specific adverse effects
  (valproate hepatotoxicity, lamotrigine rash)
• ? Age-related pharmacokinetic factors
• ? Neonate low protein binding, low metabolic
  rate, possible decreased absorption if given with
  milk/formula
• ? Children faster metabolism

128
Managing Pediatric Epilepsy
Return to index

• Consider chewable/liquid formulations
• Weight-based dosing with frequent adjustments to
  account for growth
• Minimize missed school
• Develop safety plan with family
• For intractable epilepsy consider
• Ketogenic diet
• Surgery
• Vagal nerve stimulation

129
Appendix References for Nurses
Return to index

• Journals
• ? Clinical Nursing Practice in Epilepsy
• ? Epilepsia (the Journal of the International
  League Against Epilepsy).
• ? Epilepsy Currents (Bimonthly Journal for
  American Epilepsy Society. Also on
  www.aesnet.org)
• ? Epilepsy USA Magazine, published by the
  Epilepsy Foundation. Also available on
  www.epilepsyfoundation.org.
• ? The Journal of Neuroscience Nursing (the
  Journal of the American Association of
  Neuroscience Nurses). There is a yearly index in
  the December issue by author and by topic
  (epilepsy) for easy reference.
• ? Seizure

130
Appendix References for Nurses
Return to index

• Books
• ? A Guide to Understanding and Living with
  Epilepsy, Devinsky, O, F.A. Davis Company, 1994.
• ? Anticonvulsant Prescribing Guide, PDR second
  edition, 1998, Ortho-McNeil.
• ? Clinical Epilepsy, Duncan, J.S., Shorvon,
  S.D., Fish, D.R., Churchill Livingstone, 1995.
• ? Core Curriculum for Neuroscience Nursing,
  third ed., American Association of Neuroscience
  Nursing.
• ? Epilepsy A to Z A Glossary of Epilepsy
  Terminology, Kaplan PW, Loiseau P, Fischer RS,
  Jallon P, Demos Vermande, 1995.
• ? Epilepsy in Clinical Practice A Case Study
  Approach, Wilner, A., Demos, 2000.
• ? Managing Seizure Disorders A Handbook for
  Health Care Professionals, Santilli, N.,
  Lippincott-Raven, 1996.

131
Appendix References for Nurses
Return to index

• Books, Cont.
• Seizures and Epilepsy in Childhood A guide for
  parents, third edition, Freeman JM, Vining EPG,
  Pillas DJ, Johns Hopkins Press, 2002.
• The Ketogenic Diet A Treatment for Children and
  Others with Epilepsy, Freeman JM, Kossoff EH,
  Kelly MT, Freeman JB. Demos, 2006.
• Childhood Seizures, Shinnar, S., Amir N, Branski
  D, Karger, 1995.
• Students with Seizures A manual for school
  nurses, Santilli N, Dodson WE, Walton AV. Health
  Scan Publications, 1991. (there is a section in
  this book that lists references for specific
  groups.)
• Treatment of Epilepsy Principles and Practice,
  Wyllie E, Gupta A, Lachhwani DK. 2005
• Videos
• ? The Epilepsy Foundation Catalog contains
  many videos that can be used for education for
  nurses, families and schools. The First Aid
  video is a good one. (800) EFA-1000 or
  www.epilepsyfoundation.org. (Spanish videos also
  available)

132
Appendix References for Nurses
Return to index

• Networking
• American Association of Neuroscience Nurses
  (AANN), 4700 W. Lake Avenue, Glenview, IL
  60025-1485, [phone], www.aann.org. The
  professional organization for nurses specializing
  in the neurosciences.
• American Epilepsy Society, 342 North Main Street,
  West Hartford, CT 06117-2507, [phone],
  www.aesnet.org. A membership society of
  professionals interested in epilepsy. Within the
  society are special interest groups including a
  nurses group. Contact the Society for more
  information.
• Association of Child Neurology Nurses (ACNN),
  1000 West County Road East, Suite 290, St. Paul,
  MN, 55126, [phone]. A membership
  organization of nurses interested in child
  neurology. 
• Epilepsy Foundation, eCommunities. Chat rooms
  for four different groups Women and Epilepsy
  Parents Helping Parents The Teen Chat Room and
  Living Well with Seizures. Located at
  www.epilepsyfoundation.org

133
Appendix References for Nurses
Return to index

• Web Sites
• American Association of Neuroscience Nurses
• http//www.aann.org
• American Child Neurology Nurses
• http//www.acnn.org
• American Epilepsy Society
• http//www.aesnet.org
• Epilepsy Foundation (National Office)
• http//www.epilepsyfoundation.org
• Epilepsy Therapy Development Project/Epilepsy.com
• http//www.epilepsy.com
• Nursing Care Implications
• http//www.nurseweek.com/ce/191-sb1.html

134
Appendix References for Nurses
Return to index
Reprinted with permission from the American
Association of Neuroscience Nurses
135
Appendix References for Neurologists
Return to index

• Epidemiology and classification
• Herman ST. Classification of Epileptic Seizures.
  Continuum Neurol. 2007 13(4) 13-47.
• Engel J et al. A Proposed Diagnostic Scheme for
  People with Epileptic Seizures and with Epilepsy
  Report of the ILAE Task Force on Classification
  and Terminology. Epilepsia 2001 42(6) 796-803.
  PubMed
• Hauser WA, Annegers JF, Kurland LT. Incidence of
  epilepsy and unprovoked seizures in Rochester,
  Minnesota 19351984. Epilepsia.
  199334(3)453468. PubMed
• French, JA and Pedley, TA. Management of
  Epilepsy. N Engl J Med 2008 359 166-176 PubMed

136
Appendix References for Neurologists
Return to index

• Evaluation of a first seizure
• First Seizure Trial Group. Randomized clinical
  trial on the efficacy of antiepileptic drugs in
  reducing the risk of relapse after a first
  unprovoked tonic-clonic seizure. Neurology.
  199343478483. PubMed
• Camfield P, Camfield C, Smith S, Dooley J, Smith
  E. Long-term outcome is unchanged by
  antiepileptic drug treatment after a first
  seizure a 15-year follow-up from a randomized
  trial in childhood. Epilepsia. 200243662663.
  PubMed
• Krumholz A, Wiebe S, Gronseth G, et al. Quality
  Standards Subcommittee of the American Academy of
  Neurology American Epilepsy Society. Practice
  parameter evaluating an apparent unprovoked
  first seizure in adults (an evidence-based
  review) Neurology. 200769(21)19962007.
  PubMed

137
Appendix References for Neurologists
Return to index

• Anti-epileptic drugs
• French JA, Kanner AM, Bautista J, et al. Efficacy
  and tolerability of the new antiepileptic drugs
  Neurology. 2004a 62125260. PubMed
  2004b62126173. PubMed
• Glauser T, Ben-Menachem, Bourgeois B et al. ILAE
  treatment guidelines evidence-based analysis of
  antiepileptic drug efficacy and effectiveness as
  initial monotherapy for epileptic seizures and
  syndromes. Epilepsia 2006 47(7) 1094-1120.
  PubMed
• Patsalos PN, Berry DJ, Bourgeois BF, Cloyd JC,
  Glauser TA, Johannessen SI, Leppik IE, Tomson T,
  Perucca E. Antiepileptic drugsbest practice
  guidelines for therapeutic drug monitoring A
  position paper by the Subcommission on
  therapeutic drug monitoring, ILAE Commission on
  therapeutic strategies. Epilepsia.
  20084912391276. PubMed

138
Appendix References for Neurologists
Return to index

• Anti-epileptic drugs in special populations
• Harden CL et al. Practice parameter update
  management issues for women with epilepsy.
  Neurology. 2009 Jul 1473(2)133-41. PubMed
• Rowan AJ et al. New onset geriatric epilepsy a
  randomized study of gabapentin, lamotrigine, and
  carbamazepine. Neurology. 2005 Jun
  1464(11)1868-73. PubMed
• Azar NJ and BW Abou-Khalil. Considerations in the
  Choice of an Antiepileptic Drug in the Treatment
  of Epilepsy. Seminars in Neurology. 2008 28(3)
  305-316. PubMed

139
Appendix References for Neurologists
Return to index

• Discontinuing antiepileptic drugs
• Berg AT, Shinnar S. Relapse following
  discontinuation