epilepsy english class 2010
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CLINICAL OF EPILEPSY
Dr. ASHARI BAHAR, M.Kes.,Sp.S.,FINSDEPARTMENT OF NEUROLOGY
FACULTY OF MEDICINEUNIVERSITY OF HASANUDDIN
MAKASSAR
DEFINITIONSDEFINITIONS
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
EPIDEMIOLOGY OF SEIZURES EPIDEMIOLOGY OF SEIZURES AND EPILEPSYAND 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%
ILAE ILAE CLASSIFICATION OF SEIZURESCLASSIFICATION OF SEIZURES
Seizures
Partial Generalized
Simple Partial
Complex Partial
Secondarily Generalized
Absence
Myoclonic
Atonic
Tonic
Tonic-ClonicILAE – International League Against Epilepsy
ILAE ILAE CLASSIFICATION OF SEIZURESCLASSIFICATION OF SEIZURES
Seizures
Partial Generalized
Simple Partial
Complex Partial
Secondarily Generalized
ILAE ILAE CLASSIFICATION OF SEIZURESCLASSIFICATION OF SEIZURES
Seizures
Partial Generalized
Simple Partial
With somatosensoryor special sensory symptoms
With motor signs
With autonomic symptoms or signs
With psychic or experiential symptoms
Complex Partial SeizuresComplex 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
Seizures
Partial Generalized
Complex Partial
Secondarily Generalized SeizuresSecondarily 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
Seizures
Partial Generalized
Secondarily
Generalized
ILAE ILAE CLASSIFICATION OF SEIZURESCLASSIFICATION OF SEIZURES
Seizures
Partial Generalized
Absence
Myoclonic
Atonic
Tonic
Tonic-Clonic
Typical Absence SeizuresTypical 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
Atypical Absence SeizuresAtypical 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
Myoclonic SeizuresMyoclonic 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
Seizures
Partial Generalized
Myoclonic
Tonic and Atonic SeizuresTonic and Atonic SeizuresTonic seizuresSymmetric, 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 fallsWhen milder produces head nods or jaw drops.
Consciousness usually impairedDuration - usually seconds, rarely more than 1 minuteEEG – sudden diffuse attenuation or generalized polyspike-wave
Seizures
Partial Generalized
Tonic
AtonicAtonic
Generalized Tonic-Clonic SeizuresGeneralized 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
Epilepsy SyndromesEpilepsy Syndromes
Epilepsy SyndromeGrouping of patients that share similar:– Seizure type(s) – Age of onset– Natural history/Prognosis– EEG patterns– Genetics– Response to treatment
Epilepsy SyndromesEpilepsy SyndromesEpilepsyEpilepsy
PartialPartial GeneralizedGeneralized
IdiopathicIdiopathic SymptomaticSymptomatic IdiopathicIdiopathic SymptomaticSymptomatic
Hippocampal AnatomyHippocampal Anatomy
From Chang and Lowenstein, 2003From Chang and Lowenstein, 2003
Basic Mechanisms Underlying Seizures Basic Mechanisms Underlying Seizures and Epilepsyand Epilepsy
Basic Mechanisms Underlying Basic Mechanisms Underlying Seizures and EpilepsySeizures and Epilepsy
Feedback and feed-forward inhibition, illustrated via cartoon and schematic of simplified hippocampal circuit
Babb TL, Brown WJ. Pathological Findings in Epilepsy. In: Engel J. Jr. Ed. Babb TL, Brown WJ. Pathological Findings in Epilepsy. In: Engel J. Jr. Ed. Surgical Treatment of the Epilepsies. New York: Raven Press 1987: 511-540Surgical Treatment of the Epilepsies. New York: Raven Press 1987: 511-540 ..
Epilepsy—Basic NeurophysiologyEpilepsy—Basic Neurophysiology
Causes of Hyperexcitability:
– excitatory post synaptic potentials (EPSPs)
– inhibitory post synaptic potentials (IPSPs)
– changes in voltage gated ion channels – alteration of local ion concentrations
Epilepsy—Basic NeurophysiologyEpilepsy—Basic Neurophysiology
Major Neurotransmitters in the brain:
– Glutamate– GABA– Acetylcholine– Dopamine– Serotonin– Histamine– Other modulators: neuropeptides,
hormones
Epilepsy—GlutamateEpilepsy—Glutamate The brain’s major excitatory neurotransmitter Two groups of glutamate receptors
– Ionotropic—fast synaptic transmission• Three subtypes – AMPA, kainate, NMDA• Glutamate-gated cation channels
– Metabotropic—slow synaptic transmission• G-protein coupled, regulation of second
messengers (cAMP and phospholipase C)• Modulation of synaptic activity
Modulation of glutamate receptors– Glycine, polyamine sites, Zinc, redox site
Epilepsy—GABAEpilepsy—GABA Major inhibitory neurotransmitter in the CNS Two types of receptors
– GABAA—post-synaptic, specific recognition sites, linked to CI- channel
– GABAB —presynaptic autoreceptors that reduce transmitter release by decreasing calcium influx, postsynaptic coupled to G-proteins to increase K+ current
Cellular Mechanisms of Seizure GenerationCellular Mechanisms of Seizure Generation
Excitation (too much) – Ionic—inward Na+, Ca++ currents– Neurotransmitter—glutamate,
aspartate
Inhibition (too little)– Ionic—inward CI-, outward K+
currents– Neurotransmitter—GABA
Normal CNS FunctionNormal CNS Function
Excitation Inhibition
glutamate,aspartate GABA
Modified from White, 2001
Hyperexcitability reflects both increased Hyperexcitability reflects both increased excitation and decreased inhibitionexcitation and decreased inhibition
Excitation
Inhibition
GABA
glutamate,aspartate
Modified from White, 2001
EXCITATION INCREASEEXCITATION INCREASE
SEIZURESEIZURE
EPILEPSY- A CRITICAL BALANCEEPILEPSY- A CRITICAL BALANCE
INHIBITION DECREASEINHIBITION DECREASE
SEIZURESEIZURE
•NaNa+ + channel antagonistschannel antagonists•CaCa2+2+ channel antagonists channel antagonists•Glutamate receptor antagonistsGlutamate receptor antagonists
•GABAGABAAA agonists agonists•Enhanced GABA levelsEnhanced GABA levels•KK++ channels modulators channels modulators
Synaptic Factors Modifying Neuronal Synaptic Factors Modifying Neuronal ExcitabilityExcitability
Alterations in expression of transmitter gated ionotropic channels
Post-translational changes in neurotransmitter channels
Remodeling of synapse location or configuration (deafferentation, sprouting)
Changes in gap-junction synaptic function
Non-synaptic (Extrinsic) Factors Modifying Non-synaptic (Extrinsic) Factors Modifying Neuronal ExcitabilityNeuronal Excitability
Changes in extracellular ion concentration
Changes in extracellular space
Modulation of transmitter metabolism or uptake by glial cells
Mechanisms of Generating Hyperexcitable NetworksMechanisms of Generating Hyperexcitable Networks
Excitatory axonal “sprouting”
Loss of inhibitory neurons
Loss of excitatory neurons “driving” inhibitory neurons
Change in neuronal firing properties (channelopathies)
Normal Rat Dentate Gyrus Epileptic Rat Dentate Gyrus
Epileptic Human Dentate Gyrus
Cavazos and Cross, 2006
Timm Stain Showing Mossy Fiber Timm Stain Showing Mossy Fiber SproutingSprouting
Timm stain Timm stain (black) for (black) for mossy fiber mossy fiber terminals terminals containing zinccontaining zinc
Chang and Lowenstein, 2003
Hippocampal Circuit Changes With Hippocampal Hippocampal Circuit Changes With Hippocampal SclerosisSclerosis
Longterm Hyperexcitability (Potentiation)
• Synaptic plasticity.• Change in the nature
of excit & inhib transmission.
• Recruits participation NTs & peptides.
• Change in functional & structural neuron and glia epil focus.
Oster, JM, Gutrecht, JA, Gross, PT : Epilepsy and Syncope. In HR, Hones, FH Netter (eds) : Neurology. Icon Learning system, 2005, p. 264-280.
Cavazos and Cross, 2006
EpileptogenesisEpileptogenesis
Mechanism of Epileptogenesis :
• Initiating events :– Head trauma - Hypoxia– Stroke - Status epilepticus– Infection - etc.
Schwartzkroin, PA. : Epileptogenesis. In MJ Aminoff, RB. Daroff (eds) : Encyclopedia of the Neurological Sciences. Vol 2, Amsterdam, 2003, p.288-209.
Causes of Acquired EpilepsyCauses of Acquired Epilepsy• Severe head injury
• Cerebral hemorrhage
• Brain tumor
• CNS infection
• ? Early life febrile seizures
Development of acquired epilepsyDevelopment of acquired epilepsy
Development of acquired epilepsyDevelopment of acquired epilepsy
Possible Mechanism of Delayed Possible Mechanism of Delayed EpileptogenesisEpileptogenesis
Kindling model: repeated subconvulsive stimuli resulting in electrical after discharges– Eventually lead to stimulation-induced
clinical seizures – In some cases, lead to spontaneous
seizures (epilepsy)– Applicability to human epilepsy
uncertain
Electroencephalogram (EEG)Electroencephalogram (EEG) Graphical depiction of cortical electrical activity, usually recorded from the
scalp.
Advantage of high temporal resolution but poor spatial resolution of cortical disorders.
EEG is the most important neurophysiological study for the diagnosis, prognosis, and treatment of epilepsy.
Etiology of Seizures and Etiology of Seizures and EpilepsyEpilepsy
Infancy and childhood– Prenatal or birth injury– Inborn error of metabolism– Congenital malformation
Childhood and adolescence– Idiopathic/genetic syndrome– CNS infection– Trauma
Etiology of Seizures and EpilepsyEtiology 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
Tumors, sporadic infections & metabolic dis.
Malignant tumours
Congenital & genetic conditions
HS, trauma, genetic predisposition
alcohol/drug abuseCVD
0 8020 40 60Age (years)
ETIOLOGY OF EPILEPSY BY AGE (ADAPTED FROM NASHEF)
Questions Raised by a First Questions Raised by a First SeizureSeizure
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?
Evaluation of a First SeizureEvaluation 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
Seizure PrecipitantsSeizure 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
Seizure Precipitants (cont.)Seizure Precipitants (cont.)
Metabolic and Electrolyte Imbalance Low blood glucose
(or high glucose, esp. w/ hyperosmolar state)
Low sodium Low calcium Low magnesium
Metabolic abnormalities and Metabolic abnormalities and seizuresseizures
Type Comment
HyponatremiaOsmotic shifts, disrupted ionic balance, in anoxia w/ shutdown of Na-K pump
Hypo- or hyperkalemia
Rare to cause seizure. Sometimes through hypomagnesemia
Hypo- or hypercalcemia
Usually other seizures first, such as tetany or altered consciousness
Hypoglycemia BS <50, disrupted Na/K pumpHyperthyroidism
May exacerbate epilepsy but rarely is de novo cause
BS = blood sugar.
Seizure Precipitants (cont.)Seizure Precipitants (cont.)
Stimulants/Other Pro-convulsant Intoxication IV drug use Cocaine Ephedrine Other herbal remedies Medication reduction
Medications that can lower seizure threshold Antidepressants:
BupropionTricyclics
NeurolepticsPhenothiazinesClozapine
Theophylline Isoniazid Penicillins Cyclosporin Meperidine
Seizure Precipitants (cont.)Seizure Precipitants (cont.)
EEG AbnormalitiesEEG 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
EEG AbnormalitiesEEG Abnormalities
Interictal
left temporal
sharp wave
consistent with a
diagnosis of
partial epilepsy
of left temporal
origin
EEG AbnormalitiesEEG Abnormalities
Interictal generalized
polyspike-wave complex
consistent with a
diaganosis of idiopathic
generalized epilepsy
Medical Treatment of First Medical Treatment of First SeizureSeizure
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]
Choosing Antiepileptic DrugsChoosing Antiepileptic DrugsConsiderations: Seizure typeEpilepsy syndromeEfficacyCostPharmacokinetic profileAdverse effectsPatient’s related medical conditions
(ie beneficial or deleterious effects on co-morbid conditions)
Choosing Antiepileptic DrugsChoosing Antiepileptic DrugsLimited placebo-controlled trials available,
particularly of newer AEDsSeveral 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 patient’s preference/concerns
Choice of AED for generalized epilepsy depends on predominant seizure type(s) as well as drug side-effect profile and patient’s preference/concerns
Choosing Antiepileptic DrugsChoosing Antiepileptic DrugsBroad-Spectrum Agents
ValproateFelbamateLamotrigineTopiramateZonisamideLevetiracetamRufinamide*Vigabatrin
Narrow-Spectrum Agents
Partial onset seizuresPhenytoinCarbamazepineOxcarbazepineGabapentinPregabalinTiagabineLacosamide*
AbsenceEthosuximide
* * New AEDs (approved 2008) categorization may changeNew AEDs (approved 2008) categorization may change
Choosing Antiepileptic Drugs (cont.)Choosing Antiepileptic Drugs (cont.) 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]
Choosing Antiepileptic Drugs (cont.)Choosing Antiepileptic Drugs (cont.)Monotherapy for Generalized-Onset Tonic-Clonic Seizures
Best evidence and FDA Indication:Valproate, Topiramate Also shown to be effective:Zonisamide, LevetiracetamPhenytoin, Carbamazepine (may exacerbate absence and myoclonic sz )
Lamotrigine (may exacerbate myoclonic sz of symptomatic
generalized epilepsies)
Choosing Antiepileptic Drugs (cont.)Choosing Antiepileptic Drugs (cont.)
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
Choosing Antiepileptic Drugs (cont.)Choosing Antiepileptic Drugs (cont.)
Myoclonic Seizures
Best evidence:Valproate Levetiracetam (FDA indication as adjunctive tx)Clonazepam (FDA indication)
Possibly effective: Zonisamide, Topiramate
Choosing Antiepileptic Drugs (cont.)Choosing Antiepileptic Drugs (cont.)
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
Antiepileptic Drug MonotherapyAntiepileptic Drug Monotherapy
Simplifies treatment
Reduces adverse effects
Conversion to monotherapy– Eliminate sedative drugs first– Withdraw antiepileptic drugs
slowly over several months
Antiepileptic Drug InteractionsAntiepileptic Drug Interactions 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)
Adverse Effects of AEDs: CommonAdverse Effects of AEDs: CommonTypically 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
Adverse Effects of AEDs: SeriousAdverse Effects of AEDs: SeriousTypically Idiosyncratic:
Renal stones topiramate, zonisamide
Anhydrosis, heat stroke topiramate
Acute closed-angle glaucoma topiramate
Hyponatremia carbamazepine, oxcarbazepine
Adverse Effects of AEDs: SeriousAdverse Effects of AEDs: SeriousTypically Idiosyncratic:
Aplastic anemia felbamate, zonisamide, valproate, carbamazepine
Hepatic Failure valproate, felbamate, lamotrigine, phenobarbital
Peripheral vision loss vigabatrin
Rash phenytoin, lamotrigine, zonisamide, carbamazepine
Starting AEDsStarting AEDsDiscuss likely adverse effects
Discuss unlikely but important adverse effects
Discuss likelihood of success
Discuss recording/reporting seizures, adverse effects, potential precipitants
Discontinuing AEDsDiscontinuing AEDs
Seizure freedom for 2 yearsimplies 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]
Evaluation After Seizure RecurrenceEvaluation After Seizure Recurrence Progressive pathology? Avoidable precipitant? If on AED
– Problem with compliance?– Pharmacokinetic factor?– Increase dose?– Change medication?
If not on AED– Start therapy?
Non-Drug Treatment/Lifestyle Non-Drug Treatment/Lifestyle ModificationsModifications
Adequate sleep
Avoidance of alcohol, stimulants, etc.
Avoidance of known precipitants
Stress reduction — specific techniques
Ketogenic DietKetogenic Diet 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
Alternative DietsAlternative Diets
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
Patient Selection for SurgeryPatient Selection for Surgery
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
Evaluation for SurgeryEvaluation for SurgeryHistory 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)
Surgical TreatmentSurgical Treatment 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
Epilepsy SurgeryEpilepsy SurgeryCorpus 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]
Vagus Nerve StimulatorVagus Nerve Stimulator 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
Vagal nerve stimulation ( VNS ) is a pacemaker – like
device that intermittently applies electrical
current to the vagus nerveVNS may have benefical
effects on both mood and cognition
Several VNS studies in epilepsy patients have
sugested an improvement in quality of life and mood
VAGAL NERVE STIMULATION
RISK FACTORS FOR RECURRENCE OF EPILEPTIC SEIZURE (Sperling, 1997)
Decreased risk Increased risk* Cause Idiopathic Symptomatic* Seizure type Generalized Seizure Partial seizure
(61-70% free seizure/thn) (21-28%)
* Family history No Yes,* EEG Normal Abnormal
(generalized spike-Wave pattern)
* Neurologic finding Normal Abnormal
Recurrence rate :
• Single unprovoked seizure : recurrence rate 16 – 61% (40%)
• Menurut penelitian Camfield et.al. : 4– Partial seizure, abnormal EEG, abnormal
neurologic findings : chance of recurrence 90%
– Generalized seizure, normal EEG, normal neurologic findings : chance of recurrence 30%
Marshall 2004
The majority of patients with newly-diagnosed epilepsy respond well to AEDs. Failure to do so may be due to:
An incorrect diagnosis of epilepsy An inappropriate choice of AED for the epilepsy syndrome Failure to take the prescribed AED An underlying cerebral abnormality Covert drug or alcohol abuse
TYPE OF SEIZURES AND EPILEPTIC SYNDROME
FIRST-LINE DRUG SECOND-LINE DRUG
Primary generalized Absence seizures * Myoclonic seizures * Tonic-clonic seizures Absence (Childhood) Absence (adolescence) Juvenile myoclonic epilepsy Infantil spasms (West’s syndrome) Lennox-gastaut syndr.Partial Simple partial seizures, Complex partial seizures SGTC, and partial epileptic syndrome
Ethosuximide, valproic acidValproic acid
Valproic acid , carbamazepine, phenytoinEthozuximideValproic acid Valproic acid Corticotropin
Valproic acid , lamotrigine
Carbamazepine, phenytoin
LamotrigineAcetazolamide, clonazepam, lamotrigine primidoneLamotrigine, phenobarbital,primidoneValproic acid , lamotrigineEthozuximide, clonazepam, Primidone, lamotrigineClonazepam, Valproic acid
Carbamazepine
Gabapentin, lamotrigine, phenobarbital, primidone, tiagabine, topiramate, Valproic acid
* Carbamazepine and phenytoin contraindicated Divalproex sodium may be better tolerated than valproic acid Vigabatrin may be an alternative first-line drug where available Clonazepam, felbamate, phenobarbital, primidone, or vigabatrin may be used alternatively Methsuximide may be used alternatively for any of the partial seizures or partial epilepsy syndrome.
SUMMARY (1)• Several basic principles in the
management of epilepsy– Accurate diagnosis– The choice of most effective AED
• Starting with monotherapy• Continuing with polytherapy
– Beware of the emerging mental problems• Therapy with AED is recommended :
– To prevent further seizure/single seizure which tendency to recur
– To the unprovoked seizure
• The succes/failure of treatment depends on the following factors :– Accurate diagnosis– Most effective AED– Attitude, compliabce, knowledge– Cooperation of the patient with
physician, paramedies family / relatives
SUMMARY (2)
• When the diagnosis is established :– Take AED for years– Started with first line drugs– Continued with drugs as add on drugs
• Alternative therapy for refractory epileptic seizure :– Surgery– Vagal nerve stimulation– Ketogenic diat
SUMMARY (3)