epilepsy--prof. fareed minhas

Understanding Epilepsy

Fareed A. MinhasProf. & Head

Institute of PsychiatryRawalpindi Medical College

Introduction

• Seizure: the result of excessive synchronous discharge of cortical neurons

• Convulsion: violent, involuntary contraction of voluntary muscles

• Epilepsy: a clinical condition characterized by recurrent unprovoked seizures

Definitions

Seizure

A paroxysmal and time-limited neurological event that results from abnormal neuronal activity in the brain

Epilepsy

Recurrent seizures

Prevalence

• 1.4 M in USA with 8.4 M visits to office-based neurologists

• i% in Pakistan• Chronic seizure disorder in 1-2% of general

population (6.1 per 1000)• Ten percent of general population have at least one

seizure in their lifetime• Minority groups may have higher rate

– Acquired (symptomatic) epilepsy– Socioeconomic status

Epileptic Neuron Stimulus

Repeated influx of sodium ions

Excessive Glutamate &Aspartate release

Excessive stimulation leadingto a seizure

An increase in the presynaptic release of glutamate and aspartatemay lead to excessive stimulation of the postsynaptic membrane.

PresynapticNeuron

Triggers

• Hyperventilation (absence)• Too much sleep• Too little sleep• Sensory stimuli• Emotional stress • Hormonal changes• Drug overdose or withdrawal

Classification

• Partial (focal, local)– Simple (w/o impairment of consciousness)

• With motor symptoms• With special sensory or somatosensory

symptoms• With psychic symptoms

– Complex (consciousness impaired)• Simple partial onset followed by impairment• Impaired consciousness at onset

– Secondarily generalized

Classification

• Generalized (convulsive or non-convulsive)– Onset occurs bilaterally and symmetrically – absence, atonic, clonic, myoclonic, tonic,

tonic-clonic, infantile spasms

• Unclassified seizures• Status epilepticus

Diagnosis of Seizure

History and observation

EEG

Diagnosis

• Seizure characteristics– Frequency and duration– Precipitating factors– Time of occurrence– Aura– Ictal and post-ictal state

• Laboratory– CBC – Chem panel with Mg and Ca– UA– Lumbar puncture

• PE and NE• EEG• MRI or CT

Features suggestive of seizure

Impairment of consciousness Deviation of the eyes Facial automatisms Rhythmic jerking of body parts Bladder or bowel incontinence Physical injury (e.g., tongue-biting) Pre-episode aura Post-episode confusion Family history of epilepsy

Role of EEG

Only test of brain function available in routine clinical use

Can reveal interictal “signature” of underlying epilepsy through the appearance of epileptiform discharges (spikes, sharp waves, and spike and slow-wave complexes)

Single EEG has sensitivity of 60% Sensitivity can be enhanced by repeating the test

(up to 90% for 3 EEGs) and by sleep deprivation

Evaluation of a patient with suspected seizure

Careful history Thorough neurological examination Standard labs (CBC, glucose, lytes, BUN/Cr, UA)

EEG

Brain MRI in case of abnormal exam CSF analysis in case of suspected infection

Differential diagnosis of seizures

Breathholding spells (children)REM sleep behavior (children)TicsConfusional migraineSyncopePanic attacksNarcolepsyTransient ischemic attackTransient global amnesiaPsychogenic seizures (pseudoseizures)

Management: Central issues

Destigmatization Judicious use of AEDs Recommendations about driving Pregnancy and epilepsy First-aid advice to family Options for refractory cases

Destigmatization

Demystifying superstitions Educating about nature of epilepsy Counseling about marriage and pregnancy Reassuring that epilepsy is compatible with a

normal and productive life

Driving recommendations

No driving after a seizure until seizure-free for 6 months

No driving after medication decrement until seizure-free for 6 months

Also applies to swimming, water sports and other activities in which seizure could be lethal

Pregnancy & Epilepsy

Epilepsy is compatible with marriage and motherhood

Pre-conception control is best predictor of seizure control during pregnancy

All AEDs are potentially teratogenic but seizure may carry greater risk to fetus

If possible, have patient controlled on lamotrigine prior to conception and stay the course

First-aid for acute seizure

Turn the patient on to his or her side Remove eyeglasses if any Clear the area of harmful objects Do not try to restrain movements Loosen neckwear like necktie or dupatta Do not force anything into the patient’s

mouth

No need for emergency medical help unless …Seizure doesn’t stop in 3 min., another seizure happens, or an injury has occurred

Options for refractory cases

Add 2nd or, if necessary, 3rd AED Consider surgical treatment

Requires specialized evaluation Options include temporal lobectomy,

lesionectomy (corticectomy), callosal commissurotomy, hemispherectomy

Consider Vagal Nerve Stimulator Implanted electrical stimulator of vagus,

effective as adjunct to AEDs

Treatment Goals

• Normal lifestyle • Reduce frequency of seizures

– Balance between suppression and AEs

• Encourage compliance• Assess the concerns of the patient

– Driving– Education– Relationships– Housing– Social stigma

• Epilepsy Foundation of America

Principles of Pharmacotherapy

• Positive correlation between the early initiation of therapy and the ability to control seizure activity

• Failure to control seizures may lead to an increase in seizure activity and also the occurrence of other seizure types

• “No regimen like the first regimen”


• Drug choice is based on seizure type and side effect profile

• Always start with monotherapy– ~70% of patients can be maintained with one

drug– Of 35% with unsatisfactory control, 10% will be

well-controlled on two drugs– ~20% will be medically refractory– 15% will become surgery candidates

• Success rate is 80-90% in properly selected patients• Risks include learning,memory, and general intellectual

impairment


• Seizure control may be achieved at doses corresponding to less than “normal” therapeutic serum levels; likewise, doses corresponding to higher than “normal” therapeutic serum levels may be tolerated and required by some patients

• Begin dosing at 1/3 to ¼ anticipated maintenance dose and titrate over 3-4 weeks

Judicious use of AEDs

Do not treat single uncomplicated seizure If AEDs are needed, use monotherapy as

much as possible (e.g: Tegral) Classic AEDs (phenytoin, Tegral and valproic

acid) have long experience but significant side-effects, esp. valproic acid in women

Newer agents very expensive & 2nd line therapy

Gabapentin is a weaker AED but almost no interactions and best for medically complex patients

Treatment Failure

• Number one cause of treatment failure is • AED is not considered ineffective until

patient has continued seizures AND some concentration-dependent side effects

• Substitute• Generics (Low bioavailability)• Mixed seizure types are more likely to

require more than one AED• Seizure chart a must


• Kinetics– Plasma protein binding

• Measure free instead of total– DPH

– Age• Neonates• Infants, children• Elderly

– Metabolism• Induction or inhibition of the CYP450 enzyme

system• Many AEDs have active metabolites


• Female patients– Enzyme-inducing AEDs

• PHT, PHB, Tegral , primidone

• VPA is an inhibitor

– Seizures before or during menses or at time of ovulation

• All female patients should take PNV with folate


• Pregnancy– 25-30% increased or decreased frequency– Increased VD and clearance– Altered protein binding– Increased incidence of adverse outcomes– Twice the incidence of congenital malformations

(4-6%)• PB and PHT – congenital heart malformations, facial

clefts• CBZ and VPA – spina bifida and hypospadias

– Monotherapy preferred


• Discontinuation of AEDs– Seizure-free for 2-5 years – Single type of primary GTC or partial– Neurological exam and IQ are normal– EEG normalized with treatment

• Not possible in all patients– High frequency– Repeated SE– Combination of seizure types– Development of abnormal functioning

Drugs of Choice – First Line

• Partial Seizures– Tegral , PHT, VPA– Lamotrigine, oxcarbazepine

• Generalized Seizures– Tonic-Clonic

• CBZ, PHT, VPA

– Absence• VPA, ethosuximide

– Myoclonic• Clonazepam, VPA

Summary

Seizures and epilepsy are a common problem in primary care medicine

Diagnosis relies on careful history and examination, supplemented by EEG

Treatment involves educating about the illness, judicious use of AEDs, instructions about driving and similar activities

Treatment options exist for refractory cases

Tegral is the first line therapy Tegral is effective & has low side effects

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