Clinical Epilepsy American Epilepsy Society C-Slide 1 Clinical Epilepsy: Index Hyperlinks can be used in slide-show mode: Click on topics to navigate to section.
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Clinical Epilepsy
American Epilepsy Society
C-Slide 1
Clinical Epilepsy: Index
Hyperlinks can be used in slide-show mode:
Click on topics to navigate to section. Click on Return to index to return to this page. Click on [PubMed] links to view citations in pubmed
Discontinuing antiepileptic drugs
American Epilepsy Society 2015
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Definitions
• Seizure: the manifestation of an abnormal, hypersynchronous discharge of a population of cortical neurons • Epilepsy: recurrent seizures (two or more) which are not provoked by acute systemic or neurologic insults American Epilepsy Society 2015
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Epidemiology of Seizures and Epilepsy
• • • 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% American Epilepsy Society 2015
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ILAE Classification of Seizures
Seizures
Partial Generalized Simple Partial Complex Partial Secondarily Generalized Absence Myoclonic
ILAE – International League Against Epilepsy
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Atonic Tonic Tonic-Clonic
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ILAE Classification of Seizures
Seizures
Partial
Generalized Simple Partial Complex Partial Secondarily Generalized American Epilepsy Society 2015
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ILAE Classification of Seizures
Seizures
Partial
Generalized Simple Partial With somatosensory or special sensory symptoms With motor signs With autonomic symptoms or signs With psychic or experiential symptoms American Epilepsy Society 2015
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Complex Partial Seizures
Impaired consciousness Clinical manifestations vary with site of origin and degree of spread • Presence and nature of aura • Automatisms • Other motor activity Duration typically < 2 minutes
Complex Partial
Seizures
Partial
Generalized
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Secondarily Generalized Seizures
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
Secondarily Generalized Partial
Seizures Generalized
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EEG: Partial Seizure
Right Frontal seizure
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Continuation of the same seizure with change in amplitude and frequency
EEG: Partial Seizure
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EEG: Partial Seizure
Continuation of the same seizure with spread to the other hemisphere
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EEG: Partial Seizure
Continuation of the same seizure with spread to the other hemisphere
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ILAE Classification of Seizures
Seizures Partial Generalized
Absence Myoclonic Atonic Tonic Tonic-Clonic
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Typical Absence Seizures
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 Seizures Partial Generalized
Absence
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EEG: Typical Absence Seizure
3Hz spike/slow wave complexes
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Atypical Absence Seizures
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 (<2.5 Hz) Patients often also have Atonic and Tonic seizures
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Atypical Absence Seizures
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Myoclonic Seizures
Seizures 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 Partial Generalized
Myoclonic
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American Epilepsy Society 2015
Myoclonic Seizures
Generalized polyspike-slow wave discharges
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Tonic and Atonic Seizures
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 Partial Seizures Generalized
Tonic Atonic
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Tonic and Atonic Seizures
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Generalized Tonic-Clonic
Seizures
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 Seizures Partial Generalized Tonic Clonic
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Epilepsy Syndromes
Epilepsy Syndrome • • • • • •
Grouping of patients that share similar:
Seizure type(s) Age of onset Natural history/Prognosis EEG patterns Genetics Response to treatment
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Epilepsy Syndromes
Epilepsy Partial Generalized Idiopathic
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Symptomatic Idiopathic Symptomatic C-Slide 25
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Etiology of Seizures and Epilepsy
Infancy and childhood • • Prenatal or birth injury Inborn error of metabolism • Congenital malformation • • • Childhood and adolescence Idiopathic/genetic syndrome CNS infection Trauma
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American Epilepsy Society 2015
Etiology of Seizures and Epilepsy
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 American Epilepsy Society 2015
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Questions Raised by a First Seizure
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?
American Epilepsy Society 2015
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Evaluation of a First Seizure
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
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Seizure Precipitants
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
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American Epilepsy Society 2015
Seizure Precipitants (cont.)
Metabolic and Electrolyte Imbalance Low blood glucose (or high glucose, esp. w/ hyperosmolar state) Low sodium Low calcium Low magnesium
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Metabolic abnormalities and seizures
Type
Hyponatremia Hypo- or hyperkalemia Hypo- or hypercalcemia
Comment
Osmotic shifts, disrupted ionic balance, in anoxia w/ shutdown of Na-K pump Rare to cause seizure. Sometimes through hypomagnesemia Usually other seizures first, such as tetany or altered consciousness Hypoglycemia BS <50, disrupted Na/K pump Hyperthyroidism May exacerbate epilepsy but rarely is de novo cause
BS = blood sugar.
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Seizure Precipitants (cont.)
Stimulants/Other Pro-convulsant Intoxication IV drug use Cocaine Ephedrine Other herbal remedies Medication reduction
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Seizure Precipitants (cont.)
Medications that can lower seizure threshold Antidepressants Bupropion Tricyclics Neuroleptics Phenothiazines Clozapine Theophylline Isoniazid Penicillins Cyclosporin Meperidine American Epilepsy Society 2015
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EEG Abnormalities
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
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American Epilepsy Society 2015
American Epilepsy Society 2015
EEG Abnormalities
Interictal left temporal sharp wave consistent with a diagnosis of partial epilepsy of left temporal origin C-Slide 38
American Epilepsy Society 2015
EEG Abnormalities
Interictal generalized polyspike-wave complex consistent with a diaganosis of idiopathic generalized epilepsy C-Slide 39
Medical Treatment of First Seizure
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. 1993;43:478 –483. [ PubMed ] Camfield et al. Epilepsia. 2002;43:662 –663. [ PubMed ]
American Epilepsy Society 2015
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Antiepileptic Drug (AED) Choice: Considerations
Seizure type Epilepsy syndrome Efficacy Cost Pharmacokinetic profile Adverse effects Patient ’ s related medical conditions (ie beneficial or deleterious effects on co-morbid conditions)
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American Epilepsy Society 2015
AED Choice: Attempt Monotherapy
Simplifies treatment Reduces adverse effects Conversion to monotherapy • • Eliminate sedative drugs first Withdraw antiepileptic drugs slowly over several months
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American Epilepsy Society 2015
AED Choice: More Considerations
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
: drug side-effect profile and patient ’ s preference/concerns • • Choice of AED for
generalized epilepsy
: predominant seizure type(s) drug side-effect profile and patient ’ s preference/concerns See appendix for
and Summary of AAN evidence-based guidelines
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American Epilepsy Society 2015
AED Choice by Seizure Type
Broad-Spectrum Agents
Valproate Felbamate Lamotrigine Topiramate Zonisamide Levetiracetam Rufinamide* Vigabatrin* Clobazam*
*
New AEDs (approved since 2008) American Epilepsy Society 2015
Narrow-Spectrum Agents
Partial onset seizures Phenytoin Carbamazepine Oxcarbazepine Gabapentin Pregabalin Tiagabine Lacosamide* Ezogabine* Absence Ethosuximide
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AED Choice: Focal Onset
Seizures
Best evidence:
Carbamazepine**, phenytoin**, levetiracetam, zonisamide
Also shown to be effective, weaker evidence:
Valproate**, lamotrigine**, oxcarbazepine**, topiramate**, phenobarbital**, gabapentin, vigabatrin
Limited or no data for monotherapy:
Pregabalin, lacosamide, rufinamide, ezogabine
** FDA approval for monotherapy Glauser T, Ben-Menachem E, Bourgeois B et al. In Epilepsia, 54(3):551-563, 2013.
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American Epilepsy Society 2015
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AED Choice: Generalized Onset Tonic-Clonic Seizures
Best evidence and FDA Indication: Valproate**, topiramate** Also shown to be effective: Zonisamide, levetiracetam, oxcarbazepine Phenytoin**, carbamazepine** (may exacerbate absence and myoclonic sz ) Lamotrigine (may exacerbate myoclonic sz of symptomatic generalized epilepsies) ** FDA approved for monotherapy American Epilepsy Society 2015
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AED Choice: 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 May precipitate or aggravate absence seizures: Carbamazepine, oxcarbazepine, phenobarbital, phenytoin, tiagabine, vigabatrin American Epilepsy Society 2015
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AED Choice: Myoclonic Seizures
Best evidence: Valproate Levetiracetam (FDA indication as adjunctive tx) Clonazepam (FDA indication) Possibly effective: Zonisamide, topiramate May Precipitate or Aggravate: Carbamazepine, gabapentin, oxcarbazepine, phenytoin, tiagabine, vigabatrin, and possibly lamotrigine (in JME)
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American Epilepsy Society 2015
AED Choice: Lennox-Gastaut Syndrome
Best evidence/FDA indication*: Topiramate, felbamate, clonazepam, lamotrigine, rufinamide, valproate, clobazam * FDA approval is for adjunctive treatment for all except clonazepam Some evidence of efficacy: Zonisamide, levetiracetam
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AED Mechanisms of Action
AED PHT CBZ, OXC barb, benzo ESM VPA FBM GBP LTG TPM TGB LEV ZNS PGB LCM RUF VGB Na + Channel Blockade X X X X X X X X (slow inact.) X Ca ++ Channel Blockade X X X X X X X H-current enhance ment X X Glutamate Receptor Antagonism X (NMDA glycine) X (NMDA) X (NMDA glycine) X (kainate) X (AMPA,kainate) X (kainate)
Modified from White HS and Rho JM, Mechanisms of Action of AEDs, 2010.
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GABA Enhance ment X (CBZ>OXC) X (GABA A ) X X X X (reuptake) X (metab.) Carbonic Anhydrase Inhibition X X
AED Interactions: Mechanisms
AEDs that may
induce
metabolism of other drugs: Broad spectrum inducers: carbamazepine, phenytoin, phenobarbital, primidone Selective CYP3A (at higher doses): oxcarbazepine, topiramate, felbamate AEDs that
inhibit
metabolism of other drugs: Valproate Selective CYP2C19: felbamate, topiramate and oxcarbazepine Can concentrations of phenytoin and phenobarbital AEDs that are highly
protein bound
: Valproate, phenytoin, carbamazepine, tiagabine, ezogabine Other drugs may alter metabolism or protein binding of antiepileptic drugs (especially antibiotics, chemotherapeutic agents and antidepressants)
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American Epilepsy Society 2015
AED
Phenytoin (PHT)
AED Interactions: Anticoagulation
Carbamazepine (CBZ)
Antiplatelet/ Anticoagulant
1. Warfarin 2. Aspirin Warfarin
Potential Clinical Effect
1. Increases INR* 2. Increases free PHT Decreases INR Phenobarbital (Pb) Primidone (PRM) Warfarin Decreases INR Valproic acid (VPA) 1. Warfarin 2. Aspirin 1. Slight decrease in INR 2. Increases free VPA
*AEDs increase metabolism of warfarin, but warfarin is 99% protein bound, and PHT and VPA increase warfarin
’
s free fraction.
INR = international normalized ratio.
Boggs J. In: Ettinger AB, Devinsky O, eds. Managing Epilepsy and Co-Existing Disorders. Boston: Butterworth-Heinemann; 2002:39-47.
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AED Interactions: Hormonal Contraception
Enzyme-inducing AEDs that may
decrease
contraception: the efficacy of hormonal Carbamazepine (Tegretol, Carbatrol) Clobazam (Onfi) Eslicarbazepine (Aptiom) Felbamate (Felbatol) Oxcarbazepine (Trileptal) Perampanel (Fycompa) Phenobarbital (Phenobarbital, Primidone) Phenytoin (Dilantin) Rufinamide (Banzel) Topiramate (Topamax) IUD is the preferred contraceptive method for women taking enzyme-inducing AEDs. Gaffield ME et al. Contraception 2011; 83:16 –29
. [ PubMed ] C-Slide 54
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AED Interactions:
Lamotrigine and oral contraception
Lamotrigine clearance is increased significantly by estrogen, particularly synthetic estrogens.
Oral contraceptive pills can decrease lamotrigine levels by up to 50% Lamotrigine levels may increase significantly during the placebo week IUD is the contraceptive method of choice for women taking lamotrigine Gaffield ME et al. Contraception 2011; 83:16 –29
. [ PubMed ] C-Slide 55
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AEDs: Serum Concentrations
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 ” “ toxic ” ranges. and
Patsalos et al. Epilepsia. 2008;49:1239 –1276. [ PubMed ]
American Epilepsy Society 2015
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AEDs: Common Adverse Effects
Typically dose-related: Dizziness , Fatigue , Ataxia, Diplopia all AEDs Irritability, neuropsychiatric side effects Levetiracetam, ezogabine Word-finding difficulty Topiramate Weight loss/anorexia Topiramate, zonisamide, felbamate Weight gain Valproate (also associated with polycystic ovarian syndrome ) Carbamazepine, gabapentin, pregabalin
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AEDs: Serious Adverse Effects
Typically Idiosyncratic: Renal stones Topiramate, zonisamide Anhydrosis, heat stroke Topiramate, Zonisamide Acute closed-angle glaucoma Topiramate Hyponatremia Carbamazepine, oxcarbazepine Urinary Retention Ezogabine
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AEDs: Serious Adverse Effects
Typically Idiosyncratic: Aplastic anemia Felbamate, zonisamide, valproate, carbamazepine Hepatic Failure Valproate, felbamate, lamotrigine, phenobarbital Peripheral vision loss Vigabatrin Rash Phenytoin, lamotrigine, zonisamide , carbamazepine
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American Epilepsy Society 2015
AEDs: Adverse Effects - Rash
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. 2007;68:1701 –1709. [ PubMed ]
American Epilepsy Society 2015
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AED Adverse Effects - Rash
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
American Epilepsy Society 2015
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AED-related rash in adult patients with epilepsy
▲▲ = rash rate significantly greater than average of all other AEDs (p<0.003) ▼▼ = rash rate significantly lower than average of all other AEDs (p<0.003) ▲ = trend towards significantly higher than average rash rate of all other AEDs (0.003 Arif H. et al. Neurology. 2007;68:1701 –1709. [ PubMed ] American Epilepsy Society 2015 C-Slide 62 Drugs rarely associated with rash Valproate Gabapentin Pregabalin Levetiracetam Topiramate C-Slide 63 American Epilepsy Society 2015 FDA alert 12/2007: Risk of “ dangerous or even fatal skin reactions ” such as Steven-Johnson Syndrome and Toxic epidermal necrolysis is increased in patients with HLA-B*1502 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 <1% 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-B*1502 allele before starting treatment with carbamazepine ” These patients may also be at risk with other AEDs (phenytoin, oxcarbazepine, lamotrigine) www.fda.gov American Epilepsy Society 2015 C-Slide 64 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 American Epilepsy Society 2015 C-Slide 65 Discuss likely adverse effects Discuss unlikely but important adverse effects Discuss likelihood of success Discuss recording/reporting seizures, adverse effects, potential precipitants C-Slide 66 American Epilepsy Society 2015 Seizure freedom for 2 years implies overall >60% 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. 1996;47:600–602. [ PubMed ] American Epilepsy Society 2015 C-Slide 67 Progressive pathology? Avoidable precipitant? If on AED • Problem with compliance? • • Pharmacokinetic factor? Increase dose? • Change medication? If not on AED • Start therapy? C-Slide 68 American Epilepsy Society 2015 Most medical conditions occur with increased incidence in patients with epilepsy compared to patients without it Some of these may be pathophysiologically related (stroke) and some may be less so Recurrent seizures may be feature of a cryptogenic condition that has myriad downstream manifestations (?auto-immune illness) C-Slide 69 American Epilepsy Society 2015 no epilepsy % any epilepsy % Heart HTN Stroke Arthritis 11.3 29 2.4 21.4 Face Pain 4.8 HA/Migraine 16.2 Ulcer 28.9 18.3 34 4.3 30.9 14.2 34.7 47.1 C-Slide 70 American Epilepsy Society 2015 Anxiety Generalized Anxiety Disorder Panic Attacks Affective Unipolar Depression Bipolar Disorder Psychosis Post-ictal Chronic Interictal/Schizophrenia-like American Epilepsy Society 2015 C-Slide 71 With rigorous diagnostic criteria prevalance of anxiety disorders in epilepsy patients in the community are between 14.8 - 25% (Edeh ‘87 and Jacoby ‘96) Pariente in 1991 reported an incidence of 21% of panic attacks in French Epilepsy patients compared to 3% of controls Hospital based studies show similar rates as community (Perino ‘96, Gureje ‘91) In epilepsy surgery candidates rates have been found as high as 31% (Manchanda ‘96) C-Slide 72 American Epilepsy Society 2015 Major Depression Bipolar Disorder Subsyndromal Symptoms C-Slide 73 American Epilepsy Society 2015 Conservative estimates state that 20% of Epilepsy patients will develop Depression Some estimates as high as 50 - 80% Women with significantly higher rates Rates vary regionally Studies have consistently shown that Depression increases the risk of developing Epilepsy, suggesting a common stem etiology C-Slide 74 American Epilepsy Society 2015 Lifetime prevalence of Bipolar Disorder in Epilepsy patients is 1.5 - 2% Much less common than Depression Notably, post-ictal psychosis can have a bipolar flavor, schizophreniform but with preserved affect and mild hypomania Many AED’s are mood stabilizers, most notably: Lamictal, Depakote, Tegretol, Trileptal C-Slide 75 American Epilepsy Society 2015 The most common presentation of Affective Disorders in Epilepsy patients is sub-syndromal depression They don’t meet criteria for Major Depressive Episode but can be significantly symptomatic Depressive symptoms have been shown to correlate with quality of life consistently, even when seizure frequency, type, etc. have not American Epilepsy Society 2015 C-Slide 76 Ictal Post-Ictal Interictal C-Slide 77 American Epilepsy Society 2015 Can range from a sense of being followed over the contralateral shoulder (amygdaloid focus) with mild paranoia to hallucinations of all sorts (auditory, visual, olfactory, tactile) Can be associated with EEG changes, though not frequently if awareness is unaltered Fluctuating awareness and paranoia/hallucinations with lability are hallmarks of non-convulsive status epilepticus American Epilepsy Society 2015 C-Slide 78 Often after a lucid period of 24 - 36 hours. Bizarre in nature often, religious at times, schizophreniform in content Affect often preserved with irritability or hypomania Can last hours to days to even weeks Treating with anti-psychotics for a few weeks limits intensity and duration RF include, prolonged seizures, seizures with l.o.c., bitemporal foci, clusters of seizures, GTC’s, family history of mood disorders, and longer duration of epilespy American Epilepsy Society 2015 C-Slide 79 Most commonly seen in Temporal Lobe Epilepsy of long duration with poor seizure control Post-Ictal Psychoses increase in frequency and duration and then become chronic interictal psychosis without return to baseline Very schizophreniform looking with paranoid, bizarre, religious delusional systems Require chronic anti-psychotic pharmacologic and psychosocial interventions Can occur de novo after Epilepsy Surgery American Epilepsy Society 2015 C-Slide 80 Every visit with a provider should include a discussion of psychiatric symptoms with patient and family Remember that sub-syndromal symptoms can significantly impact quality of life and respond to treatment Know when to refer to psychiatrist or therapist for ongoing treatment Depression and Anxiety should always be explored Screen for post-ictal psychosis American Epilepsy Society 2015 C-Slide 81 The most common concerns noted by patients with epilepsy: Driving (70%) Independence Work and Education Social Embarrassment Medication Dependence Mood/Stress Safety Giliam and Kuzniecky 1997 C-Slide 82 American Epilepsy Society 2015 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 C-Slide 83 American Epilepsy Society 2015 American Epilepsy Society 2015 History and Exam: consistency, localization of seizure onset and progression 3Telsa 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) C-Slide 84 C-Slide 85 • 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 C-Slide 86 American Epilepsy Society 2015 Seizure Free (except auras) Anterior Temporal Resection 66% (possibly higher with mesial temporal sclerosis) Improved Not improved 21% 14% Engel J, Jr, et al. Neurology. 2003;60:538 –547. [ PubMed ] American Epilepsy Society 2015 Neocortical Resection 49% (63% if lesional) 30% 21% C-Slide 87 C-Slide 88 Corpus Callosotomy Palliative surgery for intractable epilepsies with drop attacks (i.e. Lennox-Gastaut Syndrome) Up to 75% have > 75% reduction in atonic seizures Risk of disconnection syndromes Hemispherectomy Indicated for catastrophic hemispheric epilepsies, usually presenting in children (i.e. Rasmussen ’s 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), 525 –537. [Pubmed] American Epilepsy Society 2015 C-Slide 89 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 C-Slide 90 American Epilepsy Society 2015 Adequate sleep Avoidance of alcohol, stimulants, etc. Avoidance of known precipitants Stress reduction — specific techniques C-Slide 91 American Epilepsy Society 2015 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 >50% seizure reduction 30% with >90% reduction Side effects include kidney stones, weight loss, acidosis, dyslipidemia C-Slide 92 American Epilepsy Society 2015 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 >50% 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 C-Slide 93 American Epilepsy Society 2015 Definition • More than 5 minutes of continuous clinical or electrographic seizure activity or • Two or more sequential seizures without full recovery between seizures C-Slide 94 American Epilepsy Society 2015 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 C-Slide 95 American Epilepsy Society 2015 30 20 10 0 70 60 50 40 16-20 20-29 30-39 40-49 50-59 60-69 70-79 Age Group (Years) Towne AR et al. Epilepsia. 1994;35:27-34. 80+ C-Slide 96 American Epilepsy Society 2015 50 40 30 20 10 0 0:30-0:59 1:00-1:59 2-4 5-10 11-23 Seizure Duration (Hours) Towne AR et al. Epilepsia. 1994;35:27-34. American Epilepsy Society 2015 24+ C-Slide 97 • • • • • • • • Check emergency ABC’s 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). Thiamine 100 mg IV; 50 ml of D50 IV unless adequate glucose known. Arif H, Hirsch LJ. Semin Neurol. 2008;28:342 –354. [ PubMed ] American Epilepsy Society 2015 C-Slide 98 Benzodiazepine LORAZEPAM Route IV Dosing 0.1mg/kg MIDAZOLAM IM Nasal Buccal 0.2mg/kg Maximum Dose 4mg @ 2mg/min May repeat x1 in 5-10 min Class & Level of Evidence Class I Level A 10mg Class I Level A DIAZEPAM PR 0.2mg/kg 20mg Class IIa, Level A Brophy GM et al. Neurocrit. Care 2012; 17:3 –23 [ PubMed] C-Slide 99 American Epilepsy Society 2015 AED Fosphenytoin Rout e IV Dosing 20 PE/kg Maximum Rate of Infusion Additional Dose 150 PE/min 5 PE/kg , 10 min after loading dose Class & Level of Evidence Class IIa Level B Phenytoin Valproate Sodium IV IV 20mg/kg 50mg/min 5-10mg/kg, 10 min after loading dose Class IIa Level B 20-40 mg/kg 3-6 mg/kg/mi n 20mg/kg, 10 min after loading dose Brophy GM et al. Neurocrit. Care 2012; 17:3 –23 [ PubMed] Class IIa Level A C-Slide 100 American Epilepsy Society 2015 Infusions Initial Dose Continuous Infusion Class & Level of Evidence Adverse Effects Midazolam 0.2mg/kg @ 2mg/min 0.05-2mg/kg/hr Class IIa Level B Respiratory depression Hypotension Propofol 1-2mg/kg @ 20mcg/kg/min 30-200 mcg/kg/min Class IIb Level B Respiratory Depression Hypotension* Propofol infusion syndrome Renal Failure l Pentobarbita American Epilepsy Society 2015 5-15 mg/kg @ ≤ 50mg/min 0.5-5mg/kg/hr Class IIb Level B Brophy GM et al. Neurocrit. Care 2012; 17:3 –23 [ PubMed] Respiratory depression Hypotension Cardiac depression Paralytic Ileus Prolonged mental status depression C-Slide 101 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. 1998;339:792–8. [ PubMed ] American Epilepsy Society 2015 C-Slide 102 Syncope Cardiac (Arrhythmia) Non-Cardiac Syncope (Vasovagal, Dysautonomic) Metabolic (Hypoglycemia) Migraine Sleep Disorders (Narcolepsy) Movement Disorders (Paroxysmal Dyskinesia) Transient Ischemic Attacks American Epilepsy Society 2015 C-Slide 103 Psychogenic Seizures Malingering Panic Attacks Intermittent Explosive Disorder Breath-holding Spells C-Slide 104 American Epilepsy Society 2015 Characteristic warning, usually gradual (except with cardiac arrhythmia) Typical precipitants (except with cardiac arrhythmia) Minimal to no postictal confusion/somnolence Convulsive syncope — tonic>clonic manifestations, usually < 30 sec; usually from disinhibited brainstem structures (only rarely from cortical hypersynchronous activity) C-Slide 105 American Epilepsy Society 2015 Syncope Seizure Trigger (position, emotion, Valsalva) Common Rare Sweating & nausea Common Rare Aura (e.g. d é j à vu, smell) or unilateral symptoms Rare Hirsch et al, Merritt ’s Textbook of Neurology, 2007 American Epilepsy Society 2015 Common C-Slide 106 Pallor Syncope Seizure Common Rare Cyanosis Rare Common Loss of consciousness <20 secs Hirsch et al, Merritt ’s Textbook of Neurology, 2007 American Epilepsy Society 2015 >60 secs C-Slide 107 Syncope Seizure Automatisms Occasional Common Tongue biting, lateral Rare Occasional Frothing/hyper-salivation Rare Hirsch et al, Merritt ’s Textbook of Neurology, 2007 American Epilepsy Society 2015 Common C-Slide 108 Syncope Seizure Movements Few clonic or myoclonic jerks or brief tonic posturing Prolonged tonic phase » rhythmic clonic mvmts Duration < 15 seconds 30 -120 seconds Frothing/hyper salivation Rare Hirsch et al, Merritt ’s Textbook of Neurology, 2007 American Epilepsy Society 2015 Common C-Slide 109 Confusion/ disorientation Diffuse myalgias Syncope Seizure Rare; <30 secs Rare, brief, usually shoulders/chest Common; several mins or longer Common, hours-days Creatine kinase elevation Rare Hirsch et al, Merritt ’s Textbook of Neurology, 2007 American Epilepsy Society 2015 Common C-Slide 110 Incontinence Prolactin level Dizziness Fear Injury other than lateral tongue biting Eye movements (rolling back) Brief automatisms Hirsch et al, Merritt ’s Textbook of Neurology, 2007 American Epilepsy Society 2015 C-Slide 111 Duration Migraine 5-20 min Typical Content Laterality Associated Features B&W; straight lines; slow spread Either side Occipital Seizure 0.5-5 min Color, round, variable spread Always same side (contralateral) Altered awareness, automatisms Hirsch et al, Merritt ’s Textbook of Neurology, 2007 American Epilepsy Society 2015 C-Slide 112 10-45% of patients referred for intractable spells Females > 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 C-Slide 113 American Epilepsy Society 2015 FEATURES SUGGESTIVE OF NONEPILEPTIC PSYCHOGENIC SEIZURES Eye Closure Pelvic thrusting Opisthotonus Side-to-side head shaking Prolonged duration (>4 minutes) Stopping and starting Suggestibility C-Slide 114 American Epilepsy Society 2015 C-Slide 115 Features suggestive of Non epileptic seizures Thrashing, struggling, crying, pelvic thrusting, side-to-side rolling, wild movements Preserved consciousness with bilateral tonic or clonic mts Lack of postictal confusion Postictal crying or shouting Important Caveats Bizarre complex automatisms can occur with frontal lobe seizures Frontal lobe seizures may have bilateral convulsive movements without impairment of consciousness Posti-ictal confusion is often absent after frontal lobe seizures Aggressive and emotional behavior can occur after epileptic seizures C-Slide 116 American Epilepsy Society 2015 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 C-Slide 117 American Epilepsy Society 20105 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 American Epilepsy Society 2015 C-Slide 118 Study of 213 EMU admissions • 21% had purely nonepileptic events • • Treated as if epilepsy for a mean of 9 yrs Half treated w/ >3 AEDs • EMU yielded definitive diagnosis in 88% Smolowitz et al. American Journal of Medical Quality. 2007;22(2):117 –122. [ PubMed ] American Epilepsy Society 2015 C-Slide 119 Early Identification of Refractory Epilepsy n=525 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 n=31 Blum DE et al. Neurology. 1996;47:260–4. [ PubMed ] • 30% patients deny all seizures • Only 23% were aware of all seizures American Epilepsy Society 2015 C-Slide 120 Definition: “ Sudden, unexpected, witnessed or unwitnessed, nontraumatic and nondrowning death, occurring in benign circumstances, in an individual with epilepsy, with or without evidence for a seizure and excluding documented status epilepticus (seizure duration >30 min or seizures without recovery in between), in which postmortem examination does not reveal a cause of death ” Nashef, et al. Epilepsia 2012; 53: 227 [PMID: 22191982] American Epilepsy Society 2015 C-Slide 121 • • • • SUDEP definitions updated in 2012 to recognized that: Some cases of sudden death have insufficient information to determine cause of death Some patients with SUDEP have coexisting conditions that may (in conjunction to seizure) contribute to death (e.g. long QT syndrome) Recognize the concept of near-SUDEP, a patient resuscitated after a probable SUDEP C-Slide 122 American Epilepsy Society 2015 • • • SUDEP Epilepsia 2005;46 Suppl 11:18 • Represents about 2-18% of deaths among the general population of patients with epilepsy Forsgren et al, Likely most common disease-related cause of death in refractory epilepsy Risk of sudden death in epilepsy patients 24 X that of general population. Ficker et al, Neurology 1998; 51:1270 Epilepsy is a significant risk factor for sudden death in population-based studies. Holst et al, Epilepsia 2013; 29:1–8. C-Slide 123 American Epilepsy Society 2015 100 fold range in SUDEP incidence • • • • Rates depend on the population studied: Incidence cohort of newly diagnosed epilepsy: 0.09 per 1000 person-years Refractory epilepsy patients: 2.2-6.0 per 1000 p-y Surgical patients : 6.3-9.3 per 1000 p y Low rates in children but higher rates in adults with childhood onset epilepsy Devinsky NEJM 2011 Reviewed in Tomson, et al. Lancet neurol Med 2011; 365: [PMID: 22070477] 2008; 7: 1021 [PMID: 18805738] , Devinsky N Engl J American Epilepsy Society 2015 • • • • • Witnessed SUDEP Langan Y et al. JNNP 2000;68:211–213. [ 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. C-Slide 125 American Epilepsy Society 2015 Factors associated with increased SUDEP risk Frequent GTCs *** Symptomatic etiology Nocturnal seizures* Subtherapeutic AED levels AED polytherapy** carbamazepine use lamotrigine use Early age of epilepsy onset/longer duration of epilepsy** Male sex Mental retardation Factors associated with decreased SUDEP risk Seizure freedom Sharing bedroom/monitoring • Risk factors found in multiple studies Reviewed in Tomson, et al. Lancet neurol 2008; 7: 1021-31 [PMID: 18805738]; Hesdorffer, et al. Epilepsia 2012; 53: 249-52 [PMID: 22191685] American Epilepsy Society 2015 Witnessed, EMU-recorded, and post-mortem studies all support a seizure, typically GTC, as the terminal event • • • Three main mechanism emerge from observed cases: Primary respiratory causes: central or obstructive apnea Cerebral shutdown: diffuse post-ictal suppression of EEG preceding EKG or respiratory changes Cardiac arrhythmias/autonomic failure Friedman, et al. JCI 2013; 123: 1415 [PMID: 23524959] C-Slide 127 American Epilepsy Society 2015 Evidence suggests seizure control reduces SUDEP risk • Meta-analysis showed studies . subjects randomized to effective dose of an AED had 7-fold reduction in risk of SUDEP during the observation period compared to placebo in add-on Ryvlin et al. Lancet neurol. 2011; PMID: 21937278 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 • • • Evaluate for other therapies: surgery, VNS, diet therapy Maximize adherence to AEDs Address seizure-provocative lifestyle factors (alcohol use, sleep deprivation) Educate patients and families Seizure alert devices • Several devices (watches, bed motion detectors) exist to alert caregivers for GTC sz • Caution: none are FDA approved or proven to prevent SUDEP or other complications of seizures. American Epilepsy Society 2015 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 C-Slide 129 American Epilepsy Society 2015 Regulation varies state by state regarding: • Reporting requirements • Required seizure-free period • Favorable/unfavorable modifiers Insurance issues Employment issues Resource: www.efa.org C-Slide 130 American Epilepsy Society 2015 - 50% of pregnancies in women with epilepsy are unplanned - All women with epilepsy of reproductive age should be counseled about the effects of epilepsy and AEDs on a future pregnancy - Pregnancy planning starts with the first AED prescription for a woman of childbearing age and drug changes should be made a year before conception when possible C-Slide 131 American Epilepsy Society 2015 96% of pregnancies in mothers with epilepsy produce normal children 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 14;73(2):133-41. [PubMed] American Epilepsy Society 2015 C-Slide 132 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. Examples: Neural tube defects Cardiac defects Genitourinary defects Oral clefts Recent prospective studies have also investigated the effects of AEDs on cognitive development of exposed children C-Slide 133 American Epilepsy Society 2015 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) Polytherapy risk may be related to specific combinations of drugs, particularly combinations with valproic acid MCM risk seems to be dose-related for most drugs Holmes et al. N Engl J Med. 2001;344:1132 –1138. [ PubMed ] C-Slide 134 American Epilepsy Society 2015 Valproate has been consistently associated with poorer outcomes MCM rate with valproate monotherapy 6.2-16.3% across 5 registries Most studies show dose- related increase in risk with doses > 750mg/day Polytherapy regimens including valproate also substantially increased risk of MCM Valproate is associated with lower IQs in exposed children compared with other AEDs (10pts on average) Valproate is associated with an increased risk of autism and autism spectrum disorder in exposed children C-Slide 135 American Epilepsy Society 2015 • • • • Probably safest AEDs (range of published MCM rates) Lamotrigine (2-5.2%) • • Levetiracetam (3%) Carbamazepine (2.2-6.3%) • Phenytoin (2.9-6.7%) Probably have risk lower than valproate (more data needed) Oxcarbazepine Zonisamide Gabapentin • • • Have significant risk greater than some other AEDs Topiramate Phenobarbital Valproate Adapted from Harden CL: Continuum. 2014; 20:60 –79 [PubMed] C-Slide 136 American Epilepsy Society 2015 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 Effects on cognitive development likely occur throughout pregnancy but particularly in 3 rd trimester 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 C-Slide 137 American Epilepsy Society 2015 Before pregnancy • • • • • Confirm epilepsy diagnosis (exclude non-epileptic seizures) 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 C-Slide 138 American Epilepsy Society 2015 During pregnancy • Continue folate supplementation • • Recommend level II ultrasound Monitor AED levels at least monthly and adjust dose accordingly • Lamotrigine clearance increases dramatically over the course of pregnancy • Metabolism also increased for levetiracetam, oxcarbazepine, phenobarbital and phenytoin • Carbamazepine levels may be relatively stable, but depends on the individual patient • Patients need a post-partum dosing plan to avoid toxicity post-partum C-Slide 139 American Epilepsy Society 2015 • • • • Breastfeeding should be encouraged for most women with epilepsy Known benefits of breastfeeding likely outweigh theoretical risks of medication exposure for most drugs Six-year old breastfed children of mothers taking carbamazepine, lamotrigine, phenytoin or valproic acid monotherapy had higher IQs and verbal abilities than children who were not breastfed. No adverse effects were noted Some recommendations advise caution with drugs with longer half-lives including ethosuxamide, phenobarbital and zonisamide but concerns are mostly theoretical. More data is needed on these drugs Meador KJ et al JAMA Pediatr. 2014; 168:729 –736 [PubMed ] C-Slide 140 American Epilepsy Society 2015 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: 1935–1984. Epilepsia. 1993;34(3):453–468. [ PubMed ] French, JA and Pedley, TA. Management of Epilepsy. N Engl J Med 2008 359: 166-176 [PubMed] C-Slide 141 American Epilepsy Society 2015 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. 1993;43:478–483. [ 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. 2002;43:662–663. [ 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. 2007;69(21):1996–2007. [ PubMed ] C-Slide 142 American Epilepsy Society 2015 Anti-epileptic drugs French JA, Kanner AM, Bautista J, et al. Efficacy and tolerability of the new antiepileptic drugs Neurology. 2004a; 62:1252–60. [ PubMed ] 2004b;62:1261– 73. [ PubMed ] Glauser T, Ben-Menachem, Bourgeois B et al. Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia 2013; 54(3): 551-563. [PubMed] Patsalos PN, Berry DJ, Bourgeois BF, Cloyd JC, Glauser TA, Johannessen SI, Leppik IE, Tomson T, Perucca E. Antiepileptic drugs–best practice guidelines for therapeutic drug monitoring: A position paper by the Subcommission on therapeutic drug monitoring, ILAE Commission on therapeutic strategies. Epilepsia. 2008;49:1239–1276. [ PubMed ] C-Slide 143 American Epilepsy Society 2015 Anti-epileptic drugs in special populations Harden CL et al. Practice parameter update: management issues for women with epilepsy. Neurology. 2009 Jul 14;73(2):133-41. [PubMed] Harden CL: Pregnancy and epilepsy. Continuum (Minneap. Minn). 2014; 20:60–79 [PubMed] Rowan AJ et al. New onset geriatric epilepsy: a randomized study of gabapentin, lamotrigine, and carbamazepine. Neurology. 2005 Jun 14;64(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] C-Slide 144 American Epilepsy Society 2015 Discontinuing antiepileptic drugs Berg AT, Shinnar S. Relapse following discontinuation of antiepileptic drugs: a meta-analysis. Neurology 1994;44:601-608. [PubMed] Practice parameter: a guideline for discontinuing antiepileptic drugs in seizure-free patients-summary statement. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 1996;47:600–602. [ PubMed ] Specchio LM et al. Discontinuing antiepileptic drugs in patients who are seizure free on monotherapy. J Neurol Neurosurg Psychiatry 2002 72: 22-25 [PubMed] C-Slide 145 American Epilepsy Society 2015 Intractable epilepsy and epilepsy surgery Kwan P and MJ Brodie. Early Identification of Intractable Epilepsy. N Engl J Med. 342 (2000), 314-9. [Pubmed] Wiebe S et al. A randomized, controlled trial of surgery for temporal lobe epilepsy, N Engl J Med 345 (2001), 311–318 [Pubmed] Engel J et al. Practice parameter: temporal lobe and localized neocortical resections for epilepsy: report of the Quality Standards Subcommittee of the American Academy of Neurology, in association with the American Epilepsy Society and the American Association of Neurological Surgeons, Neurology 60 (2003), 538–547 [Pubmed] Spencer SS and L Huh, Outcomes of epilepsy surgery in adults and children . Lancet Neurol. (2008), 525–537. [Pubmed] C-Slide 146 American Epilepsy Society 2015 Management of status epilepticus Arif H, Hirsch LJ. Treatment of status epilepticus. Semin Neurol. 2008;28:342 – 354. doi: 10.1055/s-2008-1079339. [ PubMed ] Brophy GM, Bell R, Claassen J, Alldredge B, Bleck TP, Glauser T, Laroche SM, Riviello JJ, Shutter L, Sperling MR, Treiman DM, Vespa PM: Guidelines for the evaluation and management of status epilepticus. Neurocrit. Care 2012; 17:3 –23 [ PubMed] Treiman DM, Meyers PD, Walton NY, Collins JF, Colling C, Rowan AJ, Handforth A, Faught E, Callabresi VP, Uthman BM, Ramsay RE, Mamdani MB. A comparison of four treatments for generalized convulsive status epilepticus. N Engl J Med. 1998;339:792 –8. [ PubMed ] Alldredge BK, Gelb AM, Isaacs SM, Corry MD, Allen F, Ulrich S, Gottwald MD, O'Neil N, Neuhaus JM, Segal MR, Lowestein DH. A comparison of lorazepam, diazepam and placebo for the treatment of out-of-hospital status epilepticus. N Engl J Med. 2001;345:631 –7. [ PubMed ] C-Slide 147 American Epilepsy Society 2015 Seizure type or epilepsy syndrome Class I Class II Class III Level of efficacy and effectiveness evidence (in alphabetic order) Adults with partial-onset seizures 4 Children with partial-onset Seizures 1 Elderly adults with partial onset seizures 1 Adults with generalized onset tonic –clonic seizures 0 Children with generalized onset tonic –clonic seizures 0 Children with absence Seizures BECTS 1 0 1 0 1 0 0 0 34 19 3 27 14 7 JME 0 0 0 3 1 Level A: CBZ, LEV, PHT, ZNS Level B: VPA Level C: GBP, LTG, OXC, PB, TPM, VGB Level A: OXC Level B: None Level C: CBZ, PB, PHT, TPM, VPA, VGB Level A: GBP, LTG Level B: None Level C: CBZ Level A: None Level B: None Level C: CBZ, LTG, OXC, PB, PHT, TPM, VPA Level A: None Level B: None Level C: CBZ, PB, PHT, TPM, VPA Level A: ESM, VPA Level B: None Level C: LTG Level A: None Level B: None Level C: CBZ, VPA Levels A, B, C: None Glauser et al. Epilepsia 2013; 54(3): 551-563. [PubMed] C-Slide 148 American Epilepsy Society 2015 Level A = Established as useful/predictive or not useful/predictive for the given condition in the specified population. Level B = Probably useful/predictive or not useful/predictive for the given condition in the specified population. Level C = Possibly useful/predictive or not useful/predictive for the given condition in the specified population. Level U = Data inadequate or conflicting. Given current knowledge, test, predictor is unproven. French et al. Neurology. 2004a; 62:1252 –60. [ PubMed ] 2004b;62:1261 –73. [ PubMed ] American Epilepsy Society 2015 C-Slide 149 Daniel Friedman, MD (chair) Elizabeth E. Gerard, MD (past chair) Ed Garcia, MD Sara Inati, MD Mirret El-Hagrassy, MD David Ko, MD Siddhartha Nadkarni, MD Prior members: Larry Hirsch, MD (past chair) Alan Ettinger, MD American Epilepsy Society 2015 C-Slide 150AEDs: Adverse Effects - Rash
AED-related rash in Asian patients
Possible suicide risk with AEDs
Starting AEDs
Discontinuing AEDs
Evaluation After Seizure Recurrence
Medical Comorbidities of Epilepsy
Medical/Neuro Comorbidities of Epilepsy (CDC Novmeber 2013)
Psychiatric Comorbidities of Epilepsy
Anxiety and Epilepsy
Affective Disorders and Epilepsy
Major Depression and Epilepsy
Bipolar Disorder and Epilepsy
Sub-Syndromal Symptoms
Psychosis and Epilepsy
Ictal Psychosis
Post-Ictal Psychosis
Interictal Psychosis
Diagnosis of Psychiatric Symptoms in Epilepsy
Psychosocial Concerns and Quality of Life in Epilepsy
Patient Selection for
Surgery
Evaluation for Surgery
Surgical Treatment
Epilepsy Surgery Outcomes
Epilepsy Surgery
Vagus Nerve Stimulator
Non-Drug Treatment/ Lifestyle Modifications
Non-Drug Treatment/ Ketogenic Diet
Non-Drug Treatment/ Alternative Diets
Status Epilepticus
Status Epilepticus (SE)
Mortality of SE by Age
Mortality of SE by duration
SE Treatment Algorithm
Status Epilepticus: First-line Treatment Options
Status Epilepticus: Second-line Treatment Options
Refractory Status Epilepticus: Treatment Options
SE Treatment Algorithm
Differential Diagnosis of Non-epileptic Events: Physiologic
Differential Diagnosis of Non-epileptic Events: Psychogenic
Syncope
Syncope vs Seizure: Before Spell
Syncope vs Seizure: During Spell
Syncope vs Seizure: During Spell
Syncope vs Seizure: During Spell
Syncope vs Seizure: After spell
Features That Are Not Helpful in Differentiating Syncope from Seizure
Migraine aura vs. occipital seizure
Psychogenic Non-epileptic Seizures
Psychogenic Non-epileptic Seizures
Psychogenic Non-epileptic Seizures
Psychogenic Non-epileptic Seizures
Utility of epilepsy video/EEG monitoring units
Utility of epilepsy video/EEG monitoring units: Non-epileptic spells
Utility of epilepsy video/EEG monitoring units (EMU): Epilepsy
Sudden Unexplained Death in Epilepsy: SUDEP
SUDEP Definitions - Updated
Epidemiology of SUDEP
SUDEP Incidence
Sudden Unexplained Death in Epilepsy: SUDEP
SUDEP Risk Factors
SUDEP: Mechanisms
SUDEP Prevention
First Aid Tonic-Clonic Seizure
Driving and Epilepsy
Pregnancy and Epilepsy Guidelines for Management
Pregnancy and Epilepsy
Major Congenital Malformation and
Pregnancy and Epilepsy: AEDs
Pregnancy and Epilepsy:
Major Congenital Malformation and AEDs
Pregnancy and Epilepsy:
Major Congenital Malformation and AEDs
AEDs in Pregnancy
Pregnancy and Epilepsy Guidelines for Management
Pregnancy and Epilepsy Guidelines for Management
Pregnancy and Epilepsy Guidelines for Management
Breast Feeding and Epilepsy
Appendix: References for Neurologists
Appendix: References for Neurologists
Appendix: References for Neurologists
Appendix: References for Neurologists
Appendix: References for Neurologists
Appendix: References for Neurologists
Appendix: References for Neurologists
ILAE Summary Guidelines
Recommendation Levels
Clinical Epilepsy Workgroup