epilepsy subspecialty seminar oct 25, 2006. defn two or more unprovoked seizures. seizure is an...
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EpilepsyEpilepsySubspecialty seminarSubspecialty seminar
Oct 25, 2006Oct 25, 2006
defndefn
Two or more unprovoked seizures.Two or more unprovoked seizures. seizure is an abnormal electrical seizure is an abnormal electrical
activity of the brain due to hyper activity of the brain due to hyper synchronous firing of aggregates of synchronous firing of aggregates of neurons.neurons.
CONCON
• Normally there are highly differentiated Normally there are highly differentiated electrical signals with in the brain that electrical signals with in the brain that sustain the normal lifesustain the normal life
• ““Electrical rebellion” that results in to Electrical rebellion” that results in to monotonous discharge firing in synchrony monotonous discharge firing in synchrony across the brainacross the brain
• ‘‘Sacire’ to take possession of Sacire’ to take possession of
• Most prevalent of the neurological Most prevalent of the neurological disordersdisorders
Magnitude of the problemMagnitude of the problem
• World wide incidence 0.3-.0.5%World wide incidence 0.3-.0.5%
prevalence 5-10/1000prevalence 5-10/1000
• Ethiopia prevalence 5.2/1000 Ethiopia prevalence 5.2/1000
GTC 81%GTC 81%
Partial complex 13.9Partial complex 13.9
simple partial 5.7simple partial 5.7
The commonest of all neurological The commonest of all neurological problemsproblems
ClassificationClassification
• Partial and GeneralizedPartial and Generalized
• Partial when the seizure arises from Partial when the seizure arises from discreet area of the cortexdiscreet area of the cortex
• Generalized when there is clinical or EEGGeneralized when there is clinical or EEG
Manifestation of simultaneous i/v of both Manifestation of simultaneous i/v of both hemispheres .hemispheres .
• Partial sz are common ones in adultsPartial sz are common ones in adults– Temporal lobe epilepsy commonest of the Temporal lobe epilepsy commonest of the
partials szs partials szs
Classification of SeizuresClassification of Seizures
1. Partial seizures1. Partial seizuresa. Simple partial seizures (with motor, a. Simple partial seizures (with motor, sensory, autonomic, or psychic signs)sensory, autonomic, or psychic signs)b. Complex partial seizuresb. Complex partial seizuresc. Partial seizures with secondary c. Partial seizures with secondary generalizationgeneralization2. Primarily generalized seizures2. Primarily generalized seizuresa. Absence (petit mal)a. Absence (petit mal)b. Tonic-clonic (grand mal)b. Tonic-clonic (grand mal)c. Tonicc. Tonicd. Atonicd. Atonice. Myoclonice. Myoclonic3. Unclassified seizures3. Unclassified seizuresa. Neonatal seizuresa. Neonatal seizuresb. Infantile spasmsb. Infantile spasms
Partial szsPartial szs
• Simple partial no loss of consciousnessSimple partial no loss of consciousness area involved area involved →type of sz→type of sz Motor → convulsiveMotor → convulsive temporal →Auditory hallntemporal →Auditory halln → →behavioral abnbehavioral abn limbic → Psychiclimbic → PsychicPost ictal paralysis 13.5%Post ictal paralysis 13.5%Epilepsia partialis continuaEpilepsia partialis continuaJACKSONIAN marchJACKSONIAN march
•
Complex partial szComplex partial sz
• Ass with alteration in consciousnessAss with alteration in consciousness• Stereotypical auraStereotypical aura• AutomatismAutomatism• Post ictal confusionPost ictal confusion• AmnesiaAmnesia• Protean range of manifestationsProtean range of manifestations• Consider as DDx in any pt with Consider as DDx in any pt with
paroxysmal abnormal behavior esp if the paroxysmal abnormal behavior esp if the pt seems not to be fully aware of itpt seems not to be fully aware of it
concon
• Partial sz with sec generaliznPartial sz with sec generalizn Aura sterotyped clearAura sterotyped clear Generalized szsGeneralized szs--Absence szAbsence sz Common in childrenCommon in children difficult to dx difficult to dx easy to treateasy to treat transient lapses of consciousnesstransient lapses of consciousness Subtle motor manifestationsSubtle motor manifestations 70% remission rate70% remission rate classic EEG findingsclassic EEG findings
..con..con
Tonic clonicTonic clonic
the sterotype sz in the public mindthe sterotype sz in the public mind• the commonest sz of the commonest sz of metabolic abnormalitiesmetabolic abnormalities• 10% of the general popn at one time during their life10% of the general popn at one time during their life• Cx by: Loss of consciousnessCx by: Loss of consciousness tonic stiffningtonic stiffning clonic phase clonic phase Post ictal confusionPost ictal confusion Headache/muscle pain Headache/muscle pain usually lasts for a minuteusually lasts for a minute
concon
Tonic /Clonic szsTonic /Clonic szsAtonicAtonic sudden loss of postural tone sudden loss of postural tone predisposes to traumapredisposes to trauma Consciousness briefly impairedConsciousness briefly impairedMyoclonicMyoclonic brief reigonal or generalized contraction of the brief reigonal or generalized contraction of the
musclesmuscles due to metabolic disturbancedue to metabolic disturbance Part of syndromesPart of syndromes
Epilepsy syndromesEpilepsy syndromes
Juvenile myoclonic epilepsyJuvenile myoclonic epilepsy adolescentsadolescents benignbenign ass with other szass with other szLennox Gastaut syd.Lennox Gastaut syd. multiple szmultiple sz Cognitive abnCognitive abn characterstic EEGcharacterstic EEGMTLE MTLE hippocampal sclerosishippocampal sclerosis partial complex szpartial complex sz most studiedmost studied
MechanismMechanism
• Imbalance b/n excitation and inhibition Imbalance b/n excitation and inhibition of the neuronof the neuron
endogenous factorendogenous factor
Epileptogenic PPtingEpileptogenic PPting
seizureseizure
……contdcontd
• Epileptogenic HI,stroke,malignanciesEpileptogenic HI,stroke,malignancies infections,drugs..infections,drugs..• Endogenous family HxEndogenous family Hx Genetic abnormalitiesGenetic abnormalities• PP factors sleep deprivationPP factors sleep deprivation photophoto mensesmensesEpileptogenesis refers to transformation of Epileptogenesis refers to transformation of
the normal neuronal network in to that of the normal neuronal network in to that of chronically hyperexcitable onechronically hyperexcitable one
..con..con
Structural abnormalitiesStructural abnormalities selective loss of neurones selective loss of neurones (inhibitory or excitatory )(inhibitory or excitatory )
sprouting and reorganizationsprouting and reorganization chronic hyperexcitable networkchronic hyperexcitable network
Con PartialCon Partial
• Inhibitory neuronal lossInhibitory neuronal loss exicitatory neurons that stimulate the exicitatory neurons that stimulate the
inhibitory pathways are also lostinhibitory pathways are also lost• Abnormal integration of neurons with Abnormal integration of neurons with reorganizationreorganization• New neuron differentiation with formation New neuron differentiation with formation
of new synapsesof new synapses• Alteration in the composition and Alteration in the composition and
expression of GABA receptors expression of GABA receptors
MTLEMTLE
……concon
• Neuronal lossNeuronal loss
• Reorganization gradually Reorganization gradually lowers lowers
• Neurogenesis sz thresholdNeurogenesis sz threshold
MechanismMechanism
AbsenceAbsence Alteration in the circuitry b/n the thalamus Alteration in the circuitry b/n the thalamus
and the cortex and the cortex Normally the rhythm of cortical stimulation is Normally the rhythm of cortical stimulation is
influenced by thalamusinfluenced by thalamusThe thalamocortical circuit underlies the The thalamocortical circuit underlies the
physiological cortical excitation including sleepphysiological cortical excitation including sleepEither fires in a burst form or in a tonic mannerEither fires in a burst form or in a tonic mannerIn turn it is influenced by the RASIn turn it is influenced by the RAS
Thalamo cortical circuitThalamo cortical circuit
MechanismMechanism
• Developmental influencesDevelopmental influences• Cortical malformationsCortical malformations proliferationproliferation migrationmigration cortical organizationcortical organizationBeing identified using high resoln neuroimagingBeing identified using high resoln neuroimaging• Change in the neuronal microenvironment Change in the neuronal microenvironment key buffering functionkey buffering function• ChannelopathiesChannelopathies
concon
Focal Discreet lisions with Focal Discreet lisions with disruption of the balance disruption of the balance
Generalized Network abnormalitiesGeneralized Network abnormalities
Intrinsic neuronal Intrinsic neuronal abnormalitiesabnormalities
EvaluationEvaluation
Is it a seizure?Is it a seizure? DDx for SzDDx for SzDoes it have any reversible cause?Does it have any reversible cause?Is medication worth initiating?Is medication worth initiating?HX preictal, ictal post ,ictal ,frequencyHX preictal, ictal post ,ictal ,frequency family hxfamily hx drugsdrugs systemic illnessessystemic illnesses•
……ConCon
• pptin factorspptin factors• P/E look for atherosclerotic MarkersP/E look for atherosclerotic Markers signs of traumasigns of trauma skin abnormalitiesskin abnormalities neurological abnneurological abnLAB CBC,U/A, OFTsLAB CBC,U/A, OFTs electrolyteselectrolytes LPLP EEGEEG
……CONCON
• Neuroimaging MRI/CTNeuroimaging MRI/CT
• functional studiesfunctional studies
evaluationevaluation
TreatmentTreatment
• Treat the underlying causeTreat the underlying cause
• Treat the ppting factorTreat the ppting factor
• Prevent recurrence Prevent recurrence
• Address psychosocial issuesAddress psychosocial issues
General principlesGeneral principles
• The lower possible doseThe lower possible dose
• Single drugSingle drug
• Appropraite for the typeAppropraite for the type
• Start low and go slowStart low and go slow
• depends on the frequency of the szdepends on the frequency of the sz
• Side effect profile Side effect profile
• Drug interactionDrug interaction
• Clinical monitoringClinical monitoring
……concon
• Serum drug levelsSerum drug levels
• Switch to another class of drug if not Switch to another class of drug if not controlled by onecontrolled by one
• Use two drugs if single therapy of Use two drugs if single therapy of two different classes failtwo different classes fail
• Follow up acc the control of szFollow up acc the control of sz
• Issue of discontinuationIssue of discontinuation
Antiepileptic drugsAntiepileptic drugs
mode of action ion mode of action ion channels/N.transmitterschannels/N.transmitters
act on Na channels act on Na channels phenytoin,carbamaphenytoin,carbama
lamotrigine,topiramatelamotrigine,topiramate Ca channel phenytoinCa channel phenytoin GABA potentiation BarbituratesGABA potentiation Barbiturates Glutamate uptake LamotrigineGlutamate uptake Lamotrigine
Primary Primary generalizgeneralizeded
PartialPartial AbsenceAbsence Atypical Atypical absence, absence, myoclonimyoclonic,c,
atonicatonic
First lineFirst line Valproic acidValproic acid
LamotrigineLamotrigineCarbamazepineCarbamazepine
PhenytoinPhenytoin
LamotrigineLamotrigine
Valproic acidValproic acid
Valproic acidValproic acid
EthosuxamideEthosuxamideValproic acidValproic acid
AlternatiAlternativeve
PhenytoinPhenytoin
CarbamazepineCarbamazepine
TopiramateTopiramate
ZonisamideZonisamide
FelbamateFelbamate
PrimidonePrimidone
PhenobarbitalPhenobarbital
TopiramateTopiramate
LevitracetamLevitracetam
TiagabineTiagabine
ZonisamideZonisamide
GabapentineGabapentine
PrimidonePrimidone
PhenobarbitalPhenobarbital
Lamotrigine Lamotrigine ClonazepamClonazepam
LamotrigineLamotrigine
TopiramateTopiramate
ClonazepamClonazepam
FelbamateFelbamate
New vs old drugsNew vs old drugs
• The new ones are found to be The new ones are found to be as effective as those of the oldas effective as those of the old expensiveexpensive not time testednot time tested
Side effects of AEDSSide effects of AEDS
Current recommendationCurrent recommendation(American Academy Of (American Academy Of Neurology)Neurology)Patients with newly diagnosed epilepsyPatients with newly diagnosed epilepsy Who require treatment can be initiated on Who require treatment can be initiated on
standard AEDs such as carbamazepine, standard AEDs such as carbamazepine, valproic acid,phenobarbitalvalproic acid,phenobarbital ORORThe new AEDs The new AEDs
lamotrigine,gabapentin,oxcarbazine,or lamotrigine,gabapentin,oxcarbazine,or topiramatetopiramate
(evidence level A/B)(evidence level A/B)
Status epilepticusStatus epilepticus
• Continues or repititive discreet szs Continues or repititive discreet szs without regaining consciousness in without regaining consciousness in between which lasts 5 or more minutesbetween which lasts 5 or more minutes
• Medical emergencyMedical emergency• As many statuses as epilepsiesAs many statuses as epilepsies• Ass with mortality rate of 20%Ass with mortality rate of 20%• The mechanism which normally aborts The mechanism which normally aborts
a sz is losta sz is lost
EtiologyEtiology
• Drug discontinuation or incomplianceDrug discontinuation or incompliance
• Acute structural injuriesAcute structural injuries
• Remote >> abnormalitiesRemote >> abnormalities
• Metabolic abnormalitiesMetabolic abnormalities
• Drugs intoxicationsDrugs intoxications
……concon
• Status is Cx byStatus is Cx by1.1. self sustenanceself sustenance2.2. Pharmaco-resistancePharmaco-resistance3.3. Neuronal damageNeuronal damageWhich tends to worsen as time passes Which tends to worsen as time passes
withoutwithoutBeing controlledBeing controlled
PathophysiologyPathophysiology
• Milliseconds to secsMilliseconds to secs ionchannel opening/closingionchannel opening/closing Neurotransmitter modulationNeurotransmitter modulation• Secs to minutes Secs to minutes Receptor trafficingReceptor trafficing• Minutes to HrsMinutes to Hrs Plastic changesPlastic changes in neuropeptide modulators in neuropeptide modulators• Hrs to days change in Hrs to days change in gene expressiongene expression partly explains how sz becomes self sustaining and partly explains how sz becomes self sustaining and Pharmaco resistantPharmaco resistant
complicationscomplications
• HyperthermiaHyperthermia
• AspirationAspiration
• RahbdomyolysisRahbdomyolysis
• Lactic acidosisLactic acidosis
• Brain injuryBrain injury
• Pulmonary edemaPulmonary edema
TreatmentTreatment
• SupportiveSupportive
AirwaysAirways
BPBP
Fast neurological examnFast neurological examn
Draw blood/secure iv lineDraw blood/secure iv line
• Ideal situations this should take <4’Ideal situations this should take <4’
• INITIATE Rx as fast as possible INITIATE Rx as fast as possible
RxRx
……concon
Diazepam/LorazepmDiazepam/Lorazepm
IV statIV stat
Repeat another doseRepeat another dose
Secure 2Secure 2ndnd iv line iv line
Phenytoin 20mg/kg 50mg/minPhenytoin 20mg/kg 50mg/min
10mg/kg10mg/kg
..cont...cont.
Phenobarb 20mg/kg 50mg/minPhenobarb 20mg/kg 50mg/min
Repeat 10mg/kgRepeat 10mg/kg
If controlled taper for 24 hrs but If controlled taper for 24 hrs but maintain higher serum levelsmaintain higher serum levels
G/A PropofolG/A Propofol
When the bp is low consider When the bp is low consider midazolam drip .midazolam drip .
ReferencesReferences
Harrisons 16Harrisons 16thth edt edtUptudate 14.1Uptudate 14.1Lancet (vol 5 march 2006)Lancet (vol 5 march 2006)Nejm(349;13 sep 25,2003)Nejm(349;13 sep 25,2003)Nejm(2005,Tales of temporal lobeNejm(2005,Tales of temporal lobewww.neurology.comwww.neurology.com