ASSESSMENT & TREATMENT OF · 11 OU Neurology Left-sided Focal Spike OU Neurology Complex Partial Seizures K473-0208 OU Neurology ... n2009 vigabatrin Sabril n2010 clobazam Onfi n2011

David Lee Gordon, MD, FAHA Update in Stroke 2007

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ASSESSMENT & TREATMENT OF SEIZURES

2016

Jeanne Ann King, MDClinical Associate Professor

Department of NeurologyThe University of Oklahoma Health Sciences Center

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ASSESSMENT & TREATMENT OF SEIZURES

Under Accreditation Council for Continuing Medical Education guidelines disclosure must be made regarding relevant financial

relationships with commercial interests within the last 12 months.

Jeanne Ann King, MD

I have no relevant financial relationships or affiliations with commercial interests to disclose.

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Learning Objectives

n1. List the different types of seizuresn2. Correlate partial seizure symptoms &

neuro-anatomic localizationn3. Describe the differential diagnosis for

seizuresn4. Describe the principles of selection &

implementation of antiepileptic drug therapy


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US EPILEPSY STATISTICS

n 2.2 million people in the United States with epilepsy

n 10,000 people in Oklahoma alone

n 4-7/1000 people/year (.5-1%)

n 150,000 new cases/year

nSingle seizure: 9%

PREVALENCE: INCIDENCE:

>65 million people worldwide

Statistics from Institute of Medicine Report 3/2012

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THE LIFE OF AN EPILEPTICn I’ve had seizures all of my life, so it’s been an

adventure, to balance the living of today, and fear of the future.

n It effects every aspect of living; your career, fun, and even raising children; from holding a baby to driving a car, you learn that nothing is for certain.

nWorking is often difficult, your life is like a yo-yo, no matter how good of a worker you are, a few seizures and they let you go.

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THE LIFE OF AN EPILEPTIC (Cont.)

nMy friends have helped a lot, by learning about me, the person; they accept the individual, without any reservation.

nIf we could educate the world, give them the chance to know, epileptics are ordinary people; good friends and happy lives are our goals.


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OVERVIEW

nDefinitionsnDiagnosisnClassificationnTreatment

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DEFINITIONS

nA seizure is a sign or symptom of cerebral paroxysmal discharge.

nEpilepsy is a tendency to have recurrent seizures.

nThe Epilepsies are syndromes or diseases characterized by a tendency to have recurrent seizures along with other clinical characteristics.


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Old Definition of Epilepsy

nA disorder of the brain characterized by an enduring tendency to have epileptic seizures and by the neurobiologic, cognitive, psychologic, and social consequences

nDiagnosis based on at least 2 unprovoked seizures more than 24 hours apart

ILAE 2005

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ILAE (International League Against Epilepsy) Definition

Epilepsy is defined as one or more seizures with a high likelihood of recurrence, not due to another immediately triggering cause, such as low blood sugar.

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WHAT HAPPENED?

Credit to John DeToledo, MD


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Clinical question #1: Was it a seizure?

nCareful history is the most importantØ The patient may be the least helpful in some

casesØEye-witness if at all possible ØPrior spells?

nConditions That Can Mimic Epileptic SeizuresØHyperventilation, syncopeØMigraine, TIA (transient ischemic attack)ØPanic attack, psychogenic seizures

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DISORDERS THAT MAY MIMIC EPILEPSY

n Gastroesophageal Refluxn Breath-holding n Migraine

Ø ConfusionalØ BasilarØ With recurrent abdominal

pain and cyclic vomitingn Sleep disorders

(especially parasomnias)n Cerebrovascular events

Ø Pallid infantile syncopeØ Vasovagal attacksØ Vasomotor syncopeØ Cardiac arrhythmias

n Movement disordersØ Stuttering attacksØ Paroxysmal

choreoathetosisØ Nonepileptic myoclonusØ Tics and habit spasms

n Psychological disordersØ Panic disorderØ Hyperventilation Ø RageØ Pseudoseizures

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Clinical question #2: Does the patient have epilepsy?

nPrecipitated seizuresØMetabolic: Uremia, hypoglycemia,

hyperglycemia, hepatic failureØToxic: Drug overdose or withdrawalØInfectious: Meningitis/encephalitis


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Seizure vs Epilepsy

Seizures

CardiovascularDrug relatedSyncopalMetabolicToxicPoisonInfectiousFebrilePseudosz

Nonepilepsy (precipitated) Epilepsy(recurrent sz)

Idiopathic(primary)

Symptomatic(secondary)

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SEIZURE DIAGNOSIS

nPhysical/Neurological Exam

nEEGØPhotic stimulationØHyperventilationØSleep deprivation

nAnatomic studiesØCTØMRI

nSpecial studiesØSPECTØPET

n Intensive CCTV/EEG monitoring

K.Penry 1992

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Laboratory Evaluation of Patients with Seizures

nGlucose, oxygennElectrolytes, BUNnCalcium, magnesiumnDrug screennLumbar puncturenScreen for inborn errors (<5 years)

nEKG


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Electroencephalography (EEG)

nEpileptiform EEG patterns (such as spikes and sharp waves) can substantiate the diagnosis and classify focal or generalized.

nNeither a normal EEG nor interictal abnormalities alone refute or confirm the diagnosis.

n If EEG is normal, repeat with sleep-deprivation.

nVideo EEG monitoring if there is a concern about nonepileptic events or seizures do not respond to medication.

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Guideline: Management of an unprovoked first seizure in adults

nClarifies when a person’s risk for another seizure warrants medication.

nNearly 50 studies reviewednAfter a first seizure, risk for another is

greatest within the first 2 yearsnRisk varies from 21-45%

Krumholz A, Wiebe S, Gronseth GS, et al. Evidence-based guideline: management of an unprovoked first seizure in adults. Neurology2015;84:1705-1713.

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Greatest risk of another seizure

nStrong evidence in those withØPrevious brain injury: stroke, brain tumor, head

traumaØEpileptiform discharges on EEG

nModerate evidence in those withØA significant abnormality on brain imagingØNocturnal seizures


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Early Treatment

nAbout half of patients who have a first seizure will never have another seizure.

nEarly treatment lowers the risk of another seizure by 35% within the first 2 years.

nEarly treatment rather than waiting for another seizure is unlikely to increase or decrease the likelihood of remaining seizure free.

n 31% will experience a drug side effect (usually mild and reversible)

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Conclusions

nThere is no black-and-white recommendation about early treatment

nIndividual circumstances, balance of risks and benefits, and personal preferences should be taken into account and the patient should participate in the decision-making process.

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Classification

Treatment


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Seizure Classification

The International Classification of Epileptic Seizures

Clinical Observation+

EEG Findings

Partial Sz Generalized Sz

Focal orlocalization related

Bilateral initially

Widespread cerebralinvolvement

ILAE 1981

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CLASSIFICATION

nPartial seizuresØSimpleØComplex

(dyscognitive)

nGeneralized seizuresØAbsenceØMyoclonicØ Tonic-clonicØAtonic

Continual seizures: Status epilepticus

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Partial Seizure

Simple Complex

Secondarilygeneralized

consciousnessImpaired +

automatisms

consciousnesspreserved

Consciousnessimpaired

+Bilateral cerebral

involvement


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Simple Partial Seizure Features

nConsciousness intactnSigns/symptoms variable

-Motor-Somatosensory-Autonomic-Psychic

nMay have focal EEG abnormality

“Focal Motor Sz”/”Focal Sensory Sz”

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Simple Partial Seizures

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Complex Partial Seizure Features

nImpaired consciousnessnIctus duration, 1 min.nBlank starenAutomatismsnAmnesia for ictal eventnFocal EEG abnormality

“Temporal Lobe Sz”/”Psychomotor Sz”

AV Deigo-Escueta, 1992 (per RE Ramsay)


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Left-sided Focal Spike

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Complex Partial Seizures

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MRI-detected hippocampal atrophy;the most common surgically remediable epilepsy


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Types of Generalized Seizures

nTonic-clonicnClonic-tonic-clonicnClonicnTonicnAbsence (typical, atypical)nMyoclonicnAtonic

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Generalized Tonic-Clonic Seizure

nOccurs in all age groupsnInvolves complete loss of consciousnessnPreviously referred to as a “grand mal” seizure

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Absence Seizure

nMost common in childrennInvolves a brief disruption of consciousnessnPreviously referred to as a “petit mal” seizure

Between Seizures:

• Normal appearance

During Seizure:

• Vacant stare • Eyes roll upward• Lack of response

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Absence Seizure Features

nChildhood onsetnBrief loss of consciousness (10-20 sec)nStaring spellnNo post-ictal periodnSubtle myoclonic movementnSimple automatismsnEEG 3 cps spike and wave

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Generalized Spike & Wave

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Myoclonic Seizure (minor motor)

nBrief, shock-like muscle contractions (jerks)- Head- Upper extremities

nUsually bilaterally symmetricalnConsciousness preservednPrecipitated by awakening or falling asleepnMay progress into clonic or clonic-tonic

seizures


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Atonic Seizure (drop attacks)

nImpaired consciousnessnLoss of muscle tonenHead dropnFallnBrief durationnInjury common

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Treatment

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REMEDIES FOR EPILEPSYfrom Owsai Temkin, The Falling Sickness

nBlood of the tortoise.nTesticles of the hippopotamus.nFeces of the land crocodile.nRoot of strychnos gathered at the time of the

waning of the moon, put into a piece of linen, and hung around the neck.

nScrapings from the selenite stone found by night at the waxing of the moon.

nFilings of iron sharpened on whetstone from Naxos.


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ANTIEPILEPTIC DRUGS (OLDEST)

n 1857 Bromidesn 1912 phenobarbital Luminaln 1935 mephobarbital Mebaraln 1938 phenytoin Dilantinn 1946 trimethadione Tridionen 1947 mephenytoin Mesantoinn 1949 paramethadione Paradionen 1951 phenacemide Phenuronen 1952 metharbital Gemoniln 1953 phensuximide Milontinn 1954 primidone Mysoline

Ferrendeli

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1ST GENERATION ANTIEPILEPTIC DRUGS (OLD)

n 1957 methsuximide Celontinn 1957 ethotoin Peganonen 1960 ethosuximide Zarontinn 1968 diazepam Valiumn 1974 carbamazepine Tegretoln 1975 clonazepam Klonopinn 1978 valproic acid Depakenen 1981 clorazepate Tranxenen 1982 divalproex Depakote

Ferrendeli

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2ND GENERATION AEDS

n 1993 felbamate Felbatoln 1993 gabapentin Neurontinn 1994 lamotrigine Lamictaln 1996 topiramate Topamaxn 1997 tiagabine Gabitriln 1999 levetiracetam Keppran 2000 oxcarbazepine Trileptaln 2000 zonisamide Zonegrann 2005 pregabalin Lyrica


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Newer AEDs

n2008 lacosamide Vimpatn2009 rufinamide Banzeln2009 vigabatrin Sabriln2010 clobazam Onfin2011 ezogabine (retigabine) Potigan2012 perampanel Fycompan2013 eslicarbazepine Aptiomn2016 brivaracetam Briviact

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POTENTIAL ADVANTAGES OF NEW AEDS

nDifferent mechanisms of actionn Improved pharmacokinetics with less need for

therapeutic drug monitoringnFewer drug interactionsn Improved therapeutic ratiosnFewer adverse eventsn Improved tolerability in special populationsn Long-acting formulations available

Willmore LJ. Clinical pharmacology of new antiepileptic drugs. Neurology 2000;55(suppl3):S17-24.

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Considerations in the Selection of AED Therapy

§ Efficacy for seizure type§ epilepsy syndrome§ Etiology§ Side effect profile§ Safety§ Mechanism of action§ Drug interactions§ Route of elimination

§ Pharmacokinetics § Need for laboratory

monitoring§ Dosing

requirements/drugformulations

§ Speed, ease of initiation

§ Co-morbidities§ *Cost


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Female patients

nConsider effects onØOCP (oral contraceptive pills) Øteratogenicity

nPrescribe folic acid 1-4 mg (milligrams)

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Initiating Treatment

nBroad-spectrum AEDs (antiepileptic drugs) are appropriate for all seizure typesØlevetiracetam (Keppra), valproate (Depakote,

lamotrigine (Lamictal) , topiramate (Topamax)nFocal onset seizures: any AED except

ethosuximide (Zarontin) may be effectivenChoice may depend on comorbidities,

adverse events and cost (GoodRX.com)

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BROAD SPECTRUM AEDS

nVPA (valproate, Depakote)nFBM (felbamate, Felbatol)nLTG (lamictal, Lamotrigine)nTPM (topiramate, Topamax)nLVT (levetiracetam, Keppra)nZNS (zonisamide, Zonegran)nRFD (rufinamide, Banzel)nVGB (vigabatrin, Sabril)nCLB (clobazam, Onfi)nBRV (brivaracetam, Briviact)


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LIMITED SPECTRUM AEDS

nPB (phenobarbital) nPHT (phenytoin, Dilantin)nCBZ (carbamazepine, Tegretol)nGBP (gabapentin, Neurontin)nTGB (tiagabine, Gabitril)nOXC (oxcarbazepine, Trileptal)nPGB (pregabalin, Lyrica)nLCS (lacosamide, Vimpat)nPER (perampanel, Fycompa)nESL (eslicarbazepine, Aptiom)

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INDIVIDUALIZING THERAPY

nUse drug most appropriate for patient’s seizure disorder

nTitrate to effective levelnIn case of treatment failure or toxicity,

substitute an alternative agentnIf necessary, combine two nonsedating

agents (avoid phenobarbital and BZD)

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Guidelines for Combination Therapy

nAvoid combining AEDs with similar or additive side effects

nAED blood levels are available even for the new drugs


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Counseling

n Until seizure free (in most states for > 6 months):ØNo driving car (or operating high risk power

equipment)ØNo swimming alone or bathing in a closed-drain tubØNo climbing on ladders (or other high places)

n Avoid sleep deprivation & alcoholn Avoid alcoholn Mood

ØHigh rates of depression & suicidal thoughtsØAEDs sometimes can contribute

n Urge compliance with AEDØDaily schedule, pill boxØExpected side effects

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EMERGING AEDS (NONAPPROVED)

n stiripentoln talampanel n losigamonen remacemiden SGB-017 (ADCI)n PNU-151774E (or NW-

1015)n fluorofelbamaten JZP-4n propyl-

isopropylacetamide (PID)

n M-TMCDn VX-765

n valrocemiden ganaxolone (CCD 1042)n carisbamaten YP3089n 2-deoxyglucose (2DG)n NAX-5055n huperzinen T-2000n tonabersatn sulthiamen ICA-105665n seletracetamn *everolimus

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NON-MEDICATION OPTIONS

nSurgerynVagus Nerve StimulationnDeep Brain Stimulation

ØNeuropace


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Referral to neurologist

nWhen the diagnosis is in questionnWhen the patient has failed to respond to

two seizure medications (drug resistant)nIf you are uncomfortable for any reason

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Documents

ASSESSMENT & TREATMENT OF · 11 OU Neurology Left-sided Focal Spike OU Neurology Complex Partial Seizures K473-0208 OU Neurology ... n2009 vigabatrin Sabril n2010 clobazam Onfi n2011