Epilepsy

For Undergraduates
M. Ossama Abdulghani
Professor of Neuropsychiatry Ain Shams University

DEFINITION
Epileptic seizures are sudden, intermittent, recurrent, stereotyped, usually unprovoked, disturbance of consciousness, behavior, emotion, motor or sensory function that are the result of occasional abnormal sudden and excessive discharge of a set of neurons in the brain (Smith et al., 1998). Epilepsy is a condition in which seizures recur, usually spontaneously. Usually two or more unprovoked epileptic seizures are required to diagnose epilepsy (Smith et al., 1998).

EPIDEMIOLOGY
Epilepsy is the commonest serious brain disorder in every country in the world. Up to 5% of mankind may have one or more seizures at sometimes in their lives. At any time forty million people may have epilepsy, especially adolescence and old age.

EPIDEMIOLOGY (CONT.)
The reported worldwide prevalence of epilepsy is 7-9 cases per 1000 population. Approximately 20-30% of epilepsies became intractable to anticonvulsant medications.

COSTS OF EPILEPSY
The costs of epilepsy are divided into direct costs and indirect costs. Costs of epilepsy were found to be $600$6000/ patient /year in USA. Although the number of patients with intractable epilepsy is 15-20% of all patients, they account for 46% of the total cost of epilepsy.

Problems in Diagnosis of Epilepsy

1. Classification 2. Pseudoseizures 3. Epilepsy surgery

ILAE classification of epileptic seizures , 1981

I- Partial (focal, local) seizures
A. Simple partial seizures (consciousness not impaired) B. Complex partial seizures (with impairment of consciousness) C. Partial seizures evolving to secondary generalized seizures

ILAE classification of epileptic seizures , 1981

II. Generalized seizures (convulsive or nonconvulsive)
A. B. C. D. Absence seizures Myoclonic seizures Clonic, tonic, and tonic-clonic seizures Atonic seizures (astatic seizures)

III. Unclassified epileptic seizures

Semiological Classification of Seizures (Noachtar el al, 1998)

Important Concepts: Epileptogenic zone Symptomatogenic zone

Classification of Epileptic Seizures and Syndromes (Luders and Noachtar et al, 2001)
Multidimensional
Semiologic classification Syndromic classification Ictal and Interictal EEG Neuroimaging Pathologic data

Pseudoseizures
Video EEG

True seizure

Pseudoseizure

MANAGEMENT
1- Prevention: - Early diagnosis and rapid referral: Public awareness. Primary care physicians. - Preventing the prevalent etiology. 2- Treatment: - Non intractable Program (minimal requirements) - Intractable Program (optimum requirements)

MANAGEMENT (CONT.)

I. EVALUATION OF THE DIAGNOSIS: Is the patient epileptic? What type of epilepsy? What is the etiology of epilepsy? Measuring seizure variables.

MANAGEMENT (CONT.)

II. STARTING AED THERAPY: - Patients at risk of developing seizures. - Patients with single unprovoked seizures. - Patients with epilepsy.

MANAGEMENT (CONT.)
III. EVALUATE MEDICAL TREATMENT: A- Adequacy. B- Doses and dosing schedule. C- Faulty combinations. D- Side effects of AEDs. E- Non-compliance. F- Monitor serum AEDs levels. G- Generic substitution of AEDs. H- Monitor body weight.

MANAGEMENT (CONT.)
IV. ELECTROPHYSIOLOGICAL ASSESSMENT: Interictal EEG recording Ictal EEG recording V. NEUROIMAGING: MRI in a minimum of 2 orthogonal planes one of them is oblique coronal.

MANAGEMENT (CONT.)
VI. MANIPULATING MEDICAL THERAPY. - Monotherapy (versus Polytherapy). - Two first line monotherapy. - Assess at 5 elimination half lives intervals - Therapeutic level versus toxic level. - Considering polytherapy (2-3 combinations) - Intractable program.

Anti-Epileptic Drugs
Phenobarbitones Phenytoin Ethosuximide Carbamazepine Valproate
Lamotrigine Topiramate Levetiracetam Pregabalin

Benzodiazepines Paraldehyde

MANAGEMENT (CONT.)
VII. STOPPING MEDICATION: At least 2 years of seizure freedom In adults 2-5 years In children 1 year seam to be reasonable (Berg and Chadwick, 2000). VIII.CONSIDERING INTRACTABILITY.

Drugs in Common Use

Phenobarbitones Phenytoin Carbamezapine Valproate Ethosuxamide Clonazepam ACTH

New Antiepileptic drugs

Felbamate

Fosphenytoin
Gabapentin Lamotrigine

Oxcarbazepine
Vigabatrin

Topiramate Levetiracetam Pregabalin Tiagabine Zonisamide

Variables Associated with Cognitive and Behavioral Impairment

SeizureRelated Variables TreatmentRelated Variables

NonSeizureRelated Variables

Epilepsy -Effects on Cognitive function

Epilepsy related factors:
Type of epilepsy - specific syndromes Duration of epilepsy Status epilepticus Localisation of epileptogenic focus Age at onset

Seizure related factors:

Seizure type Seizure frequency

Treatment-related factors
Antiepileptic drugs (dose, type, interactions)

Epileptic seizures

Treatment/ Drugs

Cognitive and behavioural effects

Epileptic seizures

Treatment/ Drugs

Tolerability

Cognitive and behavioural effects

Epileptic seizures

Treatment/ Drugs

Lack of efficacy

Cognitive and behavioural effects

Treatment-related Factors
Poly-therapy versus mono-therapy. Higher doses versus therapeutic range doses. Type of anti-epileptic. Worse
Phenobarbital, BZD VA, CBZ, PHT New AEDs

Loring and Meador, 2001

Treatment-related Factors
Gabapentin and Lamotrigine
Tiagabine, Vigabatrin, Oxycarbazepine

Topiramate

Worse
Loring and Meador, 2001

Management Issues for Women with Epilepsy

 Over 90% of Women with Epilepsy (WWE) can expect good pregnancy outcomes. A minority of WWE will experience a worsening of seizure control during pregnancy. A coordinated approach to the care of WWE,

with contributions from a primary care provider, obstetrician, geneticist, and neurologist, is ideal.
Interdisciplinary communication for counseling and management is crucial.

WWE During Reproductive Years

There is strong evidence (class I) you should: Choose the antiepileptic drug (AED) most appropriate for seizure type; goal should be monotherapy. Counsel patients entering reproductive years about the decreased effectiveness of hormonal contraception with enzyme-inducing AEDs. Begin folic acid supplementation with at least 0.4 mg/day; continue through pregnancy.

WWE During and after Pregnancy

There is strong evidence (class I) you should:

Optimize therapy for WWE before conception.

Complete AED therapy changes at least six months before planned conception, if possible. Do not change to an alternate AED during pregnancy for the sole purpose of reducing teratogenic risk.

WWE During and after Pregnancy

There is strong evidence (class I) you should: 1. test alpha-fetoprotein levels at 14 to 16 weeks gestation. 2. Order structural ultrasound at 16 to 20 weeks gestation; and if appropriate, amniocentesis for amniotic fluid alpha-fetoprotein and acetylcholinesterase levels. 3. Encourage breast-feeding for WWE; monitor the neonate for sedation or feeding difficulties.

WWE During and after Pregnancy

There is evidence (class III) you should consider: Monitoring AED levels during pregnancy before conception, at the beginning of each trimester, and in the last month of pregnancy. Monitoring AED levels through the eighth postpartum week. You will probably be able to resume pre-pregnancy levels safely. Prescribing 10 mg per day of vitamin K in the last month of pregnancy for WWE taking enzyme-inducing AEDs.

Status Epilepticus

Definition?
First aid management? Recommended Drugs
1. IV bolus Benzodiazepines 2. Phenytoins

3. IV drip Benzo or Phenobarbitals

Thank You