Dr Anoop.K.RAsst professor,Dept of general medicine

MMCH

The following should be considered in the diff. dg. of epilepsy: Syncope attacks (when pt. is standing; results from global

reduction of cerebral blood flow; prodromal pallor, nausea, sweating; jerks!)

Cardiac arrythmias (e.g. Adams-Stokes attacks). Prolonged arrest of cardiac rate will progressively lead to loss of consciousness – jerks!

Migraine (the slow evolution of focal hemisensory or hemimotor symptomas in complicated migraine contrasts with more rapid “spread“ of such manifestation in SPS. Basilar migraine may lead to loss of consciousness!

Hypoglycemia – seizures or intermittent behavioral disturbances may occur.

Narcolepsy – inappropriate sudden sleep episodes Panic attacks PSEUDOSEIZURES – psychosomatic and personality disorders

The concern of the clinician is that epilepsy may be symptomatic of a treatable cerebral lesion.

Routine investigation: Haematology, biochemistry (electrolytes, urea and calcium), chest X-ray, electroencephalogram (EEG).Neuroimaging (CT/MRI) should be performed in all persons aged 25 or more presenting with first seizure and in those pts. with focal epilepsy irrespective of age.

Specialised neurophysiological investigations: Sleep deprived EEG, video-EEG monitoring.

Advanced investigations (in pts. with intractable focal epilepsy where surgery is considered): Neuropsychology, Semiinvasive or invasive EEG recordings, MR Spectroscopy, Positron emission tomography (PET) and ictal Single photon emission computed tomography (SPECT)

The majority of pts respond to drug therapy (anticonvulsants). In intractable cases surgery may be necessary. The treatment target is seizure-freedom and improvement in quality of life!

The commonest drugs used in clinical practice are: Carbamazepine, Sodium valproate, Lamotrigine (first line drugs) Levetiracetam, Topiramate, Pregabaline (second line drugs) Zonisamide, Eslicarbazepine, Retigabine (new AEDs)

Basic rules for drug treatment: Drug treatment should be simple, preferably using one anticonvulsant (monotherapy). “Start low, increase slow“. Add-on therapy is necessary in some patients…

Increase inhibitory neurotransmitter system—GABA

Decrease excitatory neurotransmitter system—glutamate

Block voltage-gated inward positive currents—Na+ or Ca++

Increase outward positive current—K+

Many AEDs pleiotropic—act via multiple mechanisms

dr shabeel

The brain’s major excitatory neurotransmitter Two groups of glutamate receptors

Ionotropic—fast synaptic transmission NMDA, AMPA, kainate Gated Ca++ and Gated Na+ channels

Metabotropic—slow synaptic transmission Quisqualate Regulation of second messengers (cAMP and

Inositol) Modulation of synaptic activity

Modulation of glutamate receptors Glycine, polyamine sites, Zinc, redox site

dr shabeel

NMDA receptor sites as targets Ketamine, phencyclidine, dizocilpine block

channel and have anticonvulsant properties but also dissociative and/or hallucinogenic properties; open channel blockers.

Felbamate antagonizes strychnine-insensitive glycine site on NMDA complex

AMPA receptor sites as targets Topiramate antagonizes AMPA site

dr shabeel

Major inhibitory neurotransmitter in the CNS

Two types of receptors GABAA—post-synaptic, specific

recognition sites, linked to CI- channel

GABAB —presynaptic autoreceptors, mediated by K+ currents

dr shabeel

Benzodiazepines (diazapam, clonazapam) Increase frequency of GABA-mediated

chloride channel openings Barbiturates (phenobarbital,

primidone) Prolong GABA-mediated chloride channel

openings Some blockade of voltage-dependent

sodium channels

dr shabeel

Gabapentin May modulate amino acid transport into

brain May interfere with GABA re-uptake

Tiagabine Interferes with GABA re-uptake

Vigabatrin (not currently available in US) elevates GABA levels by irreversibly

inhibiting its main catabolic enzyme, GABA-transaminase

dr shabeel

Neurons fire at high frequencies during seizures

Action potential generation is dependent on Na+ channels

Use-dependent or time-dependent Na+ channel blockers reduce high frequency firing without affecting physiological firing

dr shabeel

Phenytoin, Carbamazepine Block voltage-dependent sodium channels at

high firing frequencies—use dependentOxcarbazepine

Blocks voltage-dependent sodium channels at high firing frequencies

Also effects K+ channelsZonisamide

Blocks voltage-dependent sodium channels and T-type calcium channels

dr shabeel

Absence seizures are caused by oscillations between thalamus and cortex that are generated in thalamus by T-type (transient) Ca2+ currents

Ethosuximide is a specific blocker of T-type currents and is highly effective in treating absence seizures

dr shabeel

K+ channels have important inhibitory control over neuronal firing in CNS—repolarize membrane to end action potentials

K+ channel agonists would decrease hyperexcitability in brain

So far, the only AED with known actions on K+ channels is valproate

Retiagabine is a novel AED in clinical trials that acts on a specific type of voltage-dependent K+ channel

dr shabeel

Felbamate Blocks voltage-dependent sodium channels at

high firing frequencies May modulate NMDA receptor via strychnine-

insensitive glycine receptor

Lamotrigine Blocks voltage-dependent sodium channels at

high firing frequencies May interfere with pathologic glutamate

release Inhibit Ca++ channels?

dr shabeel

Topiramate Blocks voltage-dependent sodium channels at

high firing frequencies Increases frequency at which GABA opens Cl-

channels (different site than benzodiazepines) Antagonizes glutamate action at AMPA/kainate

receptor subtype?Valproate

May enhance GABA transmission in specific circuits

Blocks voltage-dependent sodium channels May also augment K+ channels T-type Ca2+ currents?

dr shabeel

The enzymes most involved with drug metabolism

Enzymes have broad substrate specificity, and individual drugs may be substrates for several enzymes

The principle enzymes involved with AED metabolism include CYP2C9, CYP2C19, CYP3A

dr shabeel

Inducers: Increase clearance and decrease steady-state concentrations of other drugs

Inhibitors: Decrease clearance and increase steady-state concentrations of other drugs

dr shabeel

Inducers Inhibitorsphenobarbital valproateprimidone topiramate (CYP2C19)phenytoin oxcarbazepine (CYP2C19)carbamazepine felbamate (CYP2C19)

dr shabeel

The enzymes most involved with drug metabolism

Nomenclature based upon homology of amino acid sequences

Enzymes have broad substrate specificity, and individual drugs may be substrates for several enzymes

The principle enzymes involved with AED metabolism include CYP2C9, CYP2C19, CYP3A4

Inducers Inhibitorsphenobarbital erythromycinprimidone nifedipine/verapamilphenytoin trimethoprim/sulfacarbamazepine propoxyphenetobacco/cigarettes cimetidine

valproate

Category CYP3A4 CYP2C9 CYP2C19 UGT

Inhibitor ErythromycinClarithromycinDiltiazemFluconazoleItraconazoleKetoconazoleCimetidinepropoxypheneGrapefruitjuice

VPAFluconazolemetronidazoleSertralineParoxetineTrimethoprim/sulfa

TiclopidineFelbamateOXC/MHDOmeprazole

VPA

Inducer CBZPHTPBfelbamateRifampinTPMOXC/MHD

CBZPHTPBRifampin

CBZPHTPBrifampin

CBZPHTPBOXC/MHDLTG (?)

Phenytoin CYP2C9 CYP2C19 Inhibitors: valproate, ticlopidine,

fluoxetine, topiramate, fluconazole

Carbamazepine CYP3A4 CYP2C8 CYP1A2 Inhibitors: ketoconazole, fluconazole,

erythromycin, diltiazem

Lamotrigine UGT 1A4 Inhibitor: valproate

Valproate UDP glucuronosyltransferase (UGT)

plasma concentrations of Lamotrigine, Lorazepam CYP2C19

plasma concentrations of Phenytoin, Phenobarbital Topiramate & Oxcarbazepine

CYP2C19 plasma concentrations of Phenytoin

Felbamate CYP2C19

plasma concentrations of Phenytoin, Phenobarbital

Although many AEDs can cause pharmacokinetic interactions, several newer agents appear to be less problematic.

AEDs that do not appear to be either inducers or inhibitors of the CYP system include:

GabapentinLamotrigineTiagabineLevetiracetamZonisamide

dr shabeel

First line drug for partial seizures Inhibits Na+ channels—use dependent Prodrug fosphenytoin for IM or IV administration.

Highly bound to plasma proteins. Half-life: 22-36 hours Adverse effects: CNS sedation (drowsiness,

ataxia, confusion, insomnia, nystagmus, etc.), gum hyperplasia, hirsutism

Interactions: carbamazapine, phenobarbital will decrease plasma levels; alcohol, diazapam, methylphenidate will increase. Valproate can displace from plasma proteins. Stimulates cytochrome P-450, so can increase metabolism of some drugs.

dr shabeel

First line drug for partial seizures Inhibits Na+ channels—use dependent Half-life: 6-12 hours Adverse effects: CNS sedation. Agranulocytosis and

aplastic anemia in elderly patients, rare but very serious adverse. A mild, transient leukopenia (decrease in white cell count) occurs in about 10% of patients, but usually disappears in first 4 months of treatment. Can exacerbate some generalized seizures.

Drug interactions: Stimulates the metabolism of other drugs by inducing microsomal enzymes, stimulates its own metabolism. This may require an increase in dose of this and other drugs patient is taking.

dr shabeel

Partial seizures, effective in neonates Second-line drug in adults due to more severe CNS

sedation Allosteric modulator of GABAA receptor (increase

open time) Absorption: rapid Half-life: 53-118 hours (long) Adverse effects: CNS sedation but may produce

excitement in some patients. Skin rashes if allergic. Tolerance and physical dependence possible.

Interactions: severe CNS depression when combined with alcohol or benzodiazapines. Stimulates cytochrome P-450

dr shabeel

Partial seizures Mechanims—see phenobarbital Absorption: Individual variability in rates. Not highly

bound to plasma proteins. Metabolism: Converted to phenobarbital and

phenylethyl malonamide, 40% excreted unchanged. Half-life: variable, 5-15 hours. PB ~100, PEMA 16

hours Adverse effects: CNS sedative Drug interactions: enhances CNS depressants, drug

metabolism, phenytoin increases conversion to PB

dr shabeel

Status epilepticus (IV) Allosteric modulator of GABAA receptors—

increases frequency Absorption: Rapid onset. Diazapam—rectal

formulation for treatment of SE Half-life: 20-40 hours (long) Adverse effects: CNS sedative, tolerance,

dependence. Paradoxical hyperexcitability in children

Drug interactions: can enhance the action of other CNS depressants

dr shabeel

Partial seizures, first-line drug for generalized seizures. Enhances GABA transmission, blocks Na+ channels,

activates K+ channels Absorption: 90% bound to plasma proteins Half-life: 6-16 hours Adverse effects: CNS depressant (esp. w/ phenobarbital),

anorexia, nausea, vomiting, hair loss, weight gain, elevation of liver enzymes. Hepatoxicity is rare but severe, greatest risk <2 YO. May cause birth defects.

Drug interactions: May potentiate CNS depressants, displaces phenytoin from plasma proteins, inhibits metabolism of phenobarbital, phenytoin, carbamazepine (P450 inhibitor).

dr shabeel

Absence seizures Blocks T-type Ca++ currents in thalamus Half-life: long—40 hours Adverse effects: gastric distress—pain,

nausea, vomiting. Less CNS effects that other AEDs, transient fatigue, dizziness, headache

Drug interactions: administration with valproate results in inhibition of its metabolism

dr shabeel

dr shabeel

Newer Antiepileptic drugsDrugs Mechanism of

actionFDA approved indication

Lamotrigine Inhibits voltage sensitive sodium channels Inhibits synaptic release of glutamate

as adjunctive therapy of partial seizures in patients greater than or equal to 2 years of age and Primary GTC in patients ≥ 13 years of age

Levetiracetam

Binds to synaptic vesicle protein SV2A and impedes nerve conduction

Refractory Partial seizuresRefractory JME

Gabapentin Binds to α2δ subunit of voltage gated calcium channels

Partial seizure with or without secondary generalization

Drugs Mechanism of action

FDA approved indication

Lacosamide Sodium channel modulation

Add-on for partial epilepsy

Rufinamide Sodium channel modulation

Lennox-Gastaut syndrome in children 4 years and older and adultsAtonic seizures

Zonisamide Inhibition of sodium channels & T type of calcium channel currentsDecreases GABA uptake & increases glutamate uptake

Focal seizure

Vigabatrin Irreversible inhibitor of GABA transaminase

Infantile spasmsAs an adjunctive for refractory partial epilepsy

Newer Antiepileptic drugs

Approved for add-on therapy, monotherapy in partial seizures that are refractory to other AEDs

Activity-dependent blockade of Na+ channels, may also augment K+ channels

Half-life: 1-2 hours, but converted to 10-hydroxycarbazepine 8-12 hours

Adverse effects: similar to carbamazepine (CNS sedative) but may be less toxic.

Drug interactions: less induction of liver enzymes, but can stimulate CYP3A and inhibit CYP2C19

dr shabeel

Add-on therapy for partial seizures, evidence that it is also effective as monotherapy in newly diagnosed epilepsies (partial)

May interfere with GABA uptake Absorption: Non-linear. Saturable (amino acid

transport system), no protein binding. Metabolism: none, eliminated by renal excretion Half-life: 5-9 hours, administered 2-3 times daily Adverse effects: less CNS sedative effects than

classic AEDs Drug interactions: none known

dr shabeel

Add-on therapy, monotherapy for refractory partial seizures. Also effective in Lennox Gastaut Syndrome and newly diagnosed epilepsy. Effective against generalized seizures.

Use-dependent inhibition of Na+ channels, glutamate release, may inhibit Ca++ channels

Half-life—24 hours Adverse effects: less CNS sedative effects than

classic AEDs, dermatitis potentially life-threatening in 1-2% of pediatric patients.

Drug interactions: levels increased by valproate, decreased by carbamazepine, PB, phenytoin

dr shabeel

Third-line drug for refractory partial seizures

Frequency-dependent inhibition of Na+ channels, modulation of NMDA receptor

Adverse effects: aplastic anemia and severe hepatitis restricts its use (black box)

Drug interactions: increases plasma phenytoin and valproate, decreases carbamazapine. Stimulates CYP3A and inhibits CYP2C19

dr shabeel

Add-on therapy for partial seizures Binds to synaptic vesicle protein SV2A,

may regulate neurotransmitter release Half-life: 6-8 hours (short) Adverse effects: CNS depresssion Drug interactions: minimal

dr shabeel

Add-on therapy for partial seizures Interferes with GABA reuptake Half-life: 5-8 hours (short) Adverse effects: CNS sedative Drug interactions: minimal

dr shabeel

Add-on therapy for partial and generalized seizures

Blocks Na+ channels and T-type Ca++ channels

Half-life: 1-3 days (long) Adverse effects: CNS sedative Drug interactions: minimal

dr shabeel

Add-on for refractory partial or generalized seizures. Effective as monotherapy for partial or generalized seizures, Lennox-Gastaut syndrome.

Use-dependent blockade of Na+ channels, increases frequency of GABAA channel openings, may interfere with glutamate binding to AMPA/KA receptor

Half-life: 20-30 hours (long) Adverse effects: CNS sedative Drug interactions: Stimulates CYP3A and inhibits

CYP2C19, can lessen effectiveness of birth control pills

dr shabeel

Add-on therapy for partial seizures, monotherapy for infantile spasms. (Not available in US).

Blocks GABA metabolism through actions on GABA-transaminase

Half-life: 6-8 hours, but pharmacodynamic activity is prolonged and not well-coordinated with plasma half-life.

Adverse effects: CNS sedative, ophthalmologic abnormalities

Drug interactions: minimal

dr shabeel

First consideration is efficacy in stopping seizures

Because many AEDs have overlapping, pleiotropic actions, the most appropriate drug can often be chosen to reduce side effects. Newer drugs tend to have less CNS depressant effects.

Potential of long-term side effects, pharmokinetics, and cost are other considerations

dr shabeel

Current treatmentSeizure type First line

treatmentSecond line treatment

Partial seizures CarbamazepineLamotrigineOxcarbazepineLevetiracetam

TopiramateValproateClobazamZonisamide

Generalized seizuresTonic-clonic Sodium Valproate

CarbamazepineLamotrigineClobazam

Absence EthosuximideSodium valproate

ClobazepamLamotrigine

Atypical absence ClobazepamClobazam

LamotrigineCarbamazepine

Myoclonic Sodium valproateClonazepam

LevitiracetamTopiramate

With secondary generalization First-line drugs are carbamazepine and

phenytoin (equally effective) Valproate, phenobarbital, and primidone are

also usually effective Without generalization

Phenytoin and carbamazepine may be slightly more effective

Phenytoin and carbamazepine can be used together (but both are enzyme inducers)

dr shabeel

Adjunctive (add-on) therapy where monotherapy does not completely stop seizures—newer drugs felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, and zonisamide

Lamotrigine, oxcarbazepine, felbamate approved for monotherapy where phenytoin and carbamazepine have failed.

Topirimate can effective against refractory partial seizures.

dr shabeel

Tonic-clonic, myoclonic, and absence seizures—first line drug is usually valproate

Phenytoin and carbamazepine are effective on tonic-clonic seizures but not other types of generalized seizures

Valproate and ethoxysuximide are equally effective in children with absence seizures, but only valproate protects against the tonic-clonic seizures that sometimes develop. Rare risk of hepatoxicity with valproate—should not be used in children under 2.

dr shabeel

Clonazepam, phenobarbital, or primidone can be useful against generalized seizures, but may have greater sedative effects than other AEDs

Tolerance develops to clonazepam, so that it may lose its effectiveness after ~6 months

Carbamazepine may exacerbate absence and myoclonic, underscoring the importance of appropriate seizure classification

Lamotrigine, topiramate, and zonisamide are effective against tonic-clonic, absence, and tonic seizures

dr shabeel

A condition when consciousness does not return between seizures for more than 30 min. This state may be life-threatening with the development of pyrexia, deepening coma and circullatory collapse. Death occurs in 5-10%.

Status epilepticus may occur with frontal lobe lesions (incl. strokes), following head injury, on reducing drug therapy, with alcohol withdrawal, drug intoxication, metabolic disturbances or pregnancy.

Treatment: AEDs intravenously ASAP, event. general anesthesia with propofol or thipentone should be commenced immediately.

Treatment Diazepam, lorazapam IV (fast, short acting)

Followed by phenytoin, fosphenytoin, or

phenobarbital (longer acting) when control is

established

dr shabeel

No evidence that any new AED was superior in efficacy to old AEDs Eg. CBZ and VPA in efficacy in well-controlled trials of recent-onset epilepsy.

Although seizure control may have improved in rare epilepsies (Vigabatrin for West-Syndrome , Felbamate for LGS), but , seizure control has not improved dramatically in the last 30 years for common seizures (focal, myoclonic and absence)

Further, one in three patients has drug resistant seizures.

Recent advances…FDA

approved drugs

New applications of existing

drugs

New formulatio

ns in pipeline

Drugs in pipeline

Clobazam

• Acts by potentiation of GABAnergic transmission via binding to GABA-A receptor

A benzodiazepine with low tendency to produce sedation Lower incidence of loss of therapeutic effect over time,

rendering it appropriate for long term management

• Oct 2011: FDA approved for Clobazam as adjunctive treatment for seizures associated with Lennox-Gestaut syndrome in adults and children 2 years of age and older in a dose of 5-40 mg/day.

Effectiveness was established in two multi-centre controlled studies.

• Most common adverse effects: sedation, lethargy and fatigue

In Dec 2013, FDA issued warning against serious skin reactions that can result in permanent harm and death and approved label changes

Ng YT, Conry JA, Drummond R, Stolle J, Weinberg MA; OV-1012 Study Investigators. Randomized, phase III study results of Clobazam in Lennox-Gastaut syndrome. Neurology. 2011 Oct 11;77(15):1473-81

Ezogabine• First neuronal potassium channel opener developed for the

treatment of epilepsy

Acts by enhancement of potassium currents mediated by

KCNQ ion channels, thereby reducing hyper excitability

Also potentiates GABA-A receptors via activation of beta 1 &

beta 2 subtype of GABA receptor

Also, weakly blocks sodium and calcium channels

Nov 2011: FDA approved Ezogabine as an adjunctive treatment in

refractory partial-onset seizures based on RESTORE I & II trials

Owen RT Ezogabine: a novel antiepileptic as adjunctive therapy for partial onset seizures. Drugs Today 2010 Nov;46(11):815-22

Ezogabine (Retigabine)• Absorption is unaffected by food with an absolute

bioavailability of 50–60%• Peak plasma concentration within 1.5 h and half life is 8 – 11

hours

• Not metabolized by the cytochrome P450 system, so minimal drug interactions seen, as below,

Phenytoin & Carbamazepine decrease Ezogabine concentration

Ezogabine inhibits renal clearance of digoxin Alcohol can increase serum Ezogabine concentrations

Serious adverse effects include urinary retention, neuropsychiatric symptoms and QT-interval lengthening that need careful monitoring

French J A et al. Randomized, double-blind, placebo-controlled trial of ezogabine (retigabine) in partial epilepsy. Neurology.2011 May 3; 76(18): 1555-63

Oxcarbazepine ER• Acts by blockade of voltage sensitive sodium channels Less potent enzyme inducer than carbamazepine

• Oct 2012: FDA approved a once-daily extended-release formulation as an adjunctive therapy for partial seizures in adults and in children > 6 years

• Dose: 1200 – 2400 OD on empty stomach

• PROSPER study, a multicentre, randomized, double-blind trial in 366 patients with refractory partial epilepsy showed efficacy

• Most common adverse effects include headache, dizziness and diplopia

Rare and Serious adverse effects are hyponatremia and suicidal ideation

French JA, Baroldi P, Brittain ST, Johnson JK; PROSPER Investigators Study Group. Efficacy and safety of extended-release oxcarbazepine (Oxtellar XR™) as adjunctive therapy in patients with refractory partial-onset seizures: a randomized controlled trial. Acta Neurol Scand. 2014 Mar;129(3):143-53

Eslicarbazepine• Third generation AED

• S-licarbazepine: effective component of carbamazepine

with,

fewer cognitive and psychiatric adverse effects

crosses BBB more effectively

lacks a toxic epoxide

minimal interaction with the cytochrome P450 liver

enzymes

Elger et al. showed less incidence of hyponatremia

compared to oxcarbazepineElinor Ben-Menachem. Eslicarbazepine Acetate: A Well-Kept Secret? Epilepsy Curr. Jan 2010; 10(1): 7–8

• Acts by blockade of fast acting voltage gated sodium channels

• Nov 2013: US FDA approved as an adjunctive treatment for partial onset seizures

• Based on 3 randomized, double blind, multi-centre trials in 1049 patients with partial onset seizures

• Dose: 400-1200 mg/day ; once daily dosing

• Most adverse effects include headache, nausea, ataxia, tremors

Eslicarbazepine

Gil-Nagel A, Elger C, Ben-Menachem E, Halász P, Lopes-Lima J, Gabbai AA, Nunes T, Falcão A, Almeida L, da-Silva PS. Efficacy and safety of eslicarbazepine acetate as add-on treatment in patients with focal-onset seizures: integrated analysis of pooled data from double-blind phase III clinical studies. Epilepsia. 2013 Jan;54(1):98-107

Parampanel• First-in-class drug, a highly selective, non competitive AMPA

type glutamate receptor antagonist

• Nov 2012: FDA approved for treatment of refractory partial-onset seizures in patients 12 years and older,

based on 3 clinical trials in 1037 adults and adolescents which showed reduced seizure frequency

Dose: 4 – 12 mg OD

• Boxed warning about the risk for serious neuropsychiatric events

• Common adverse effects include dizziness, fatigue, irritability, anxiety, aggression, etc

Steinhoff BJ, Ben-Menachem E, Ryvlin P, Shorvon S, Kramer L, Satlin A, Squillacote D, Yang H, Zhu J, Laurenza A. Efficacy and safety of adjunctive perampanel for the treatment of refractory partial seizures: a pooled analysis of three phase III studies. Epilepsia. 2013 Aug;54(8):1481-9

Topiramate –extended release

Blockage of voltage-dependent sodium channels

Augmentation of the activity of the neurotransmitter GABA

Antagonism of the AMPA/ kainate subtype of the glutamate

receptor

• March 2014: US FDA approved

As monotherapy for focal seizure and primary GTC in

patients > 10 years and,

As an adjunctive therapy in patients > 2 years for focal

seizures, primary GTC and seizures associated with

Lennox-Gestaut syndrome.

Withdrawal should be carried out only if pt is satisfied that a further attack would not ruin employment etc. (e.g. driving licence). It should be performed very carefully and slowly! 20% of pts will suffer a further sz within 2 yrs.

The risk of teratogenicity is well known (~5%), especially with valproates, but withdrawing drug therapy in pregnancy is more risky than continuation. Epileptic females must be aware of this problem and thorough family planning should be recommended. Over 90% of pregnant women with epilepsy will deliver a normal child.

A proportion of the pts with intractable epilepsy will benefit from surgery.

Epilepsy surgery procedures: Curative (removal of epileptic focus) and palliative (seizure-related risk decrease and improvement of the QOL)

Curative (resective) procedures: Anteromesial temporal resection, selective amygdalohippocampectomy, extensive lesionectomy, cortical resection, hemispherectomy.

Palliative procedures: Corpus callosotomy and Vagal nerve stimulation (VNS).

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