EPILEPSY

EPILEPSY

DR. MANSOUR AL MOALLEM

Definitions:

An epileptic seizure is an abnormal and excessive focal or generalized discharge of neurons usually accompanied by an observable behavioral abnormality.

It is a symptom of the brain hyper-excitability which may affect otherwise normal individuals (e.g. with ECT, head trauma).

Epilepsy is a prediposistion to recurrent epileptic seizure, with various etiologies.

Seizures are paroxysmal discrete events although they may recur in close succession without an intervening return to normal consciousness producing a state called status epilepticus . Generalized convulsive status epilepticus may be life threatening if not terminated within a few hours.

Seizures usually spontaneous or provoked by nonspecific factors increasing brain excitability such as sleep deprivation, drug or alcohol ingestion or withdrawal or hypoglycemia.

Rare patients have their seizures provoked consistently by specific sensory stimuli (e.g. flickering lights, video games or television, a specific piece of music, reading, immersion in hot water, etc.): the reflex epilepsy.

Epidemiology of Epilepsy

• 5% - 7% will have a seizure at sometime during their life

• 1% - 2% of the population suffers from epilepsy

• Peak age incidence: newborn, first decade, elderly

• In only 50% is an etiology identifiable

• 80% respond well to treatment

Is Epilepsy Inherited?

Genetic factors play only a minor role in most type of epilepsy. Certain inherited diseases, which are rare, have epilepsy as one of their manifestations. Absence seizures have a tendency to run in families. In general, a child with an epileptic parent has about a 5% chance of developing epilepsy.

Major Causes of Seizures in Different Age Groups

Etiology

Of seizure

Newborn Infancy Childhood Adolescence

Young Adult

Old

Adult

Perinatal injury * *

Metabolic defect * *

Congenital Malformation

* *

Infection * *

Genetic epilepsy * * *

Genetic disease * * * *

Postnatal trauma * * * *

Brain tumor * *

Vascular disease *

Classification of SeizuresInternational classification of seizures

A) Partial (focal) seizures - with or without

secondary generalization)

1-Simple Partial

a) motor

b) sensory

c) autonomic

d) psychic

Classification of SeizuresInternational classification of seizures

Classification of Seizures (cont)

2-Complex Partial (with or without automatisms)

a) impairment of consciousness at onset

b) simple partial onset followed by

impairment of consciousness

Classification of Seizures (cont)

B) Genleraized seizures

a) Tonic-clonic (Grand Mal)

b) Absence (typical Petit Mal or atypical)

c) Myoclonic

d) Clonic

e) Atonic

Simple Partial Seizures (Focal)

• Seizure in which the first clinical and EEG changes indicates initial activation of a system of neurons limited to part of one cerebral hemisphere but where there is no alteration of consciousness.

• Clinical symptoms, is determined by the anatomical location of the seizure focus. May be: motor signs, sensory symptoms, autonomic signs and symptoms, psychic symptoms.

• May evolve to complex partial or secondarily generalized tonic-clonic seizure.

Complex Partial Seizures (Psychomotor)

• Impaired consciousness associated with automatic behaviour

• The phases (in temporolimbic seizure): stare, stereotyped automatisms, reactive automatisms

• May evolve from simple partial seizure and to a secondarily generalized tonic-clonic seizure

• Occur in 40% of patients with epilepsy• Most common seizure type seen in adult• 50% of patients have onset in childhood

• Drugs control seizure in less than ½ of patients

• Disabling psychosocial disturbances develop in 1/3

Tonic-Clonic Seizure (Grand Mal)

• Abrupt loss of consciousness (may be vague ill-described warning but no true aura

• Sudden sharp bilaterally symmetrical contraction muscles, cry, fall, head extension, cyanosis. May be tongue-biting and incontinence

• Bilaterally symmetrical clonic jerks, may be salivation and frothing at the mouth

• Deep respiration and relaxation of muscles• Post-ictal period of depressed consciousness, usually

awakens with muscle stiffness and sometimes headache

Absence Seizures (Petit Mal)

• Sudden onset brief (usually <10 sec) interruption of ongoing activities

• Blank stare, usually unresponsive when spoken to

• May have stereotyped motor automatisms (mild clonic or tonic), especially if prolonged

• Abrupt onset and abrupt cessation

• No post-ictal confusion or other symptoms

Atypical Absence Seizures

• Alteration of consciousness which may not be complete (some activities may continue in obtunded child.

• May have loss of tone of face and neck muscles and/or myoclonic twitching of the eyelids and mouth.

• Onset and cessation gradual.

Myoclonic Seizures

• Sudden very brief shock-like muscular contractions.

• May be generalized or confined to the face and trunk, to one or more extremities, or to individual muscles or group of muscles.

• May be regularly repetitive or sporadic.• May occur in other neurological conditions

as well as epilepsy.

Tonic Seizure

• Brief generalized tonic contraction; head extension, stiffening of all four extremities.

• Tachycardia; apnea, then cyanosis.

• Frequently seen in Lennox-Gastaut Syndrome, especially during slow wave sleep.

Clonic Seizures

• Rapidly repetitive bilateral jerking of extremities and facial muscles and loss of consciousness.

• May be accompanied by autonomic changes.

• Post-ictal phase is usually short.

Atnoic Seizures (Drop Attacks)

• Sudden diminution in muscles tone, which may be fragmentary.

• Extremely brief or no loss of consicouness.• May occur repetitively in a rythmic,

successive manner.• Atonic seizure frequently seen in Lennox-

Gastaut Syndrome; drop attacks may occur in neurological condition other than epilepsy.

Pseudoseizures

• Atypical features (e.g. Partial preservation of consciousness during convulsion)

• Tendency to occur in company.

• Triggered by emotional upset.

• Urinary incontinence, tongue-biting, injury are unusual.

• Poor psychosocial history.

• Unresponsive to appropriate AED therapy.

Pseudoseizures (cont)

• 5-20% of outpatient epilepsy population have pure pseudoseizures.

• 20-30% of uncontrolled epileptic also have pseudoseizures.

• 20-30% of pseudoseizure patients also have epilepsy.

• F:M 3-4: 1

• 85% of cases are between 15 and 25 years old.

Differential Diagnosis

• Syncope• Psychogenic pseudoseizures• Panic/anxiety/HV attacks• Movement disorders• Sleep disorders (narcolepsy, parasomnias)• Hypoglycemia• TIA΄s• Migraine• Pheochromocytoma

Investigations

• Electroencephalogram EEG

• CT scan brain / MRI brain

Treatment

The Principles :1-Accurate diagnosis2-Accurate seizure classification and if possible

syndromic diagnosis3-Select the most effective drug for seizure type 4-Begin with monotherapy5-Allow the adequate time to assess the effect of the

drug6-If the seizure are not controlled, obtain blood levels7-Change gradually to a second drug if the first drug Does not control the seizures

Mechanisms of Action of Anti-epileptic Drugs

Mechanism

Reduction of membrane excitability by blocking

Voltage-dependent Na channels.

Drugs

Phenytoin

Valproate

Lamotrigine

Blockage of Calcium-T channels in the thalamic relay neurons

Ethosuximide

possibly Valproate

Enhancement of GABA inhibitory action Benzodiazepine

Barbiturates

Figabatrin

Possibly Valproate

Reduction of glutamate excitatory action Lamotrigine

Unknown Gabapentin

Antiepileptic Drugs of ChoiceSeizure Type 1st Choice

Monotherapy

Alternative

Monotherapy

Add-on Agent & Others

Generalized

Tonic-clonic VPACBZ

PB

PRM

CLB

LTG

VGB

Absence VPA

ESM

CLB AZM

LTG

Myoclonic VPA NZP AZM

LTG

Atonic VPA NZP CLB

LTG

Partial

Simple or

Complex

-/+secondary gen..

CBZ

PHT

VPA

PB

PRM

CLB

GBP

LTG / VGB

Legends

AZM= acetazolamide

CZB= clonazepam

LTG= lamotrigine

PHT= phenytoin

VPA= valproic acid

CBZ= carbamazepine

ESM= ethosuximide

NZP= nitrazepam

PRM= primidone

CLB= clobazam

GBP= gabapentin

PB= phenobarbitone

VGB= vigabatrin

Factors associated with an increased probability of seizure recurrence following

medication withdrawal

• Longstanding, severe epilepsy, initial difficult to control• Structural brain damage and neurological handicap• Partial seizures and mixed seizures• Persistent epileptic findings on EEG• Specific syndromes which are known not remit

e.g. juvenile myoclonic epilepsy• Adult onset epilepsy

Surgical Treatment of Epilepsy

• Seizure uncontrolled with medical therapy or intolerable side effects

• Good cognitive function• Identifiable focus (except for callosotomy)• Social support system

International Classification of Epilepsies and Epilepsy Syndromes

1- Localization-related (focal, local, partial) epilepsies and epileptic syndromes A. Idiopathic with age-related onset 1. Benign childhood epilepsy with centrotemporal spikes 2. Childhood epilepsy with occipital paroxysms B. Symptomatic

2-Generalized epilepsies and epileptic syndrome

A- Idiopathic with age-related onset

1. Benign neonatal epilepsy

2. Childhood absence epilepsy (pyknolepsy)

3. Juvenile myoclonic epilepsy (impulsive

petit mal)

4. Juvenile absence epilepsy with generalized

tonic-clonic seizures on awakening

B- Secondary (idiopathic or symptomatic)

1. West syndrome (infantile spasms) 2. Lennox-Gastaut syndrome

C- Symptomatic

1. Nonspecific etiology (early myoclonic encephalopathy 2. Specific syndromes (epileptic seizures that may complicate many diseases, e.g.Ramsy Hunt syndrome, Unverrichs disease

STATUS EPILEPTICUSSTATUS EPILEPTICUS

What is the defenition?

STATUS EPILEPTICUSSTATUS EPILEPTICUS

DefinitionDefinition..

Seizure persists for 30 minutes, Seizure persists for 30 minutes, OROR two or two or more sequential seizure without full more sequential seizure without full recovery of the consciousness between recovery of the consciousness between the seizuresthe seizures..

EpidemiologyEpidemiology

• 60 per 100,000 individuals per year in the general 60 per 100,000 individuals per year in the general populationpopulation

• Bimodal distribution, high value during the first year of Bimodal distribution, high value during the first year of life and over the age of 60life and over the age of 60

• Mortality around 22% (pediatric 3%, adult 26% and Mortality around 22% (pediatric 3%, adult 26% and elderly 38%)elderly 38%)

Determined byDetermined by::– ageage– seizure durationseizure duration– etiology etiology

EtiologyEtiology..Majority of patient with SE did not have a history Majority of patient with SE did not have a history

of epilepsy (38% of children, 40-50% of adult of epilepsy (38% of children, 40-50% of adult and 30% of elderly did not a history of and 30% of elderly did not a history of epilepsy).epilepsy).

In adult:In adult:• Low anticonvulsant drug level 34%Low anticonvulsant drug level 34%• Remote symptomaticRemote symptomatic

( hemorrhage, tumor) 25%( hemorrhage, tumor) 25%• CVA 22% CVA 22% In children:In children:• InfectionInfection• FeverFever• Electrolyte disturbanceElectrolyte disturbance

Why high morbidity & mortality…

Metabolic Complication Associated Metabolic Complication Associated with status epilepticuswith status epilepticus

• Metabolic & othersMetabolic & others– Lactic acidosisLactic acidosis– HypercapniaHypercapnia– HypoglycemiaHypoglycemia– HyperkalemiaHyperkalemia– HyponatremiaHyponatremia– DehydrationDehydration– leukocytosisleukocytosis

Medical complication SE (cont)Medical complication SE (cont)

• AutonomicAutonomic– HyperpyrexiaHyperpyrexia– Failure of cerebral autoregulationFailure of cerebral autoregulation– VomitingVomiting– IncontinenceIncontinence

• RenalRenal

.. Prerenal asotemia Prerenal asotemia – Renal failure from rhabdomyolysisRenal failure from rhabdomyolysis

Medical complication SE (cont)Medical complication SE (cont)

• Cardiac/RespiratoryCardiac/Respiratory– HypoxiaHypoxia– ArrhythmiaArrhythmia– High blood pressureHigh blood pressure– High output failureHigh output failure– Pulmonary edemaPulmonary edema– PneumoniaPneumonia

• CognitiveCognitive– Intellectual impairment with memory lossIntellectual impairment with memory loss

How you treat…

ManagementManagement.. The goal should always be The goal should always be immediate diagnosis and termination of immediate diagnosis and termination of seizuresseizures..

• HistoryHistory : From the companion/previous : From the companion/previous

notesnotes

• ExaminationExamination: :

General / systemic / NeurologicalGeneral / systemic / Neurological

• InvestigationsInvestigations::

) ) 11 ( (CBC / deferentialCBC / deferential

ElectrolytesElectrolytes

Blood sugarBlood sugar

Investigations (cont)Investigations (cont)

(2)(2) EEGEEG

(3)(3) ECG / X-ray / ABGECG / X-ray / ABG

(4)(4) CT scan brain or MRI brain CT scan brain or MRI brain

TreatmentTreatment

(1)(1) Monitor vital signsMonitor vital signs(2)(2) I.V. lineI.V. line

(3)(3) 0022

(4)(4) Anti-epileptic drugs (AED)Anti-epileptic drugs (AED)

The drug should be administered The drug should be administered I.V.I.V. for for rapid absorption without reacting with rapid absorption without reacting with other medications or solutions.other medications or solutions.

Specific Drug CompoundsSpecific Drug Compounds..

1- 1- BenzodiazepinesBenzodiazepines (BZD) (BZD)Diazepam / Lorazepam / MidazolamDiazepam / Lorazepam / Midazolam

• Work by enhancing GABA ergic inhibition Work by enhancing GABA ergic inhibition by binding to the BZD-GABA, and by binding to the BZD-GABA, and barbiturate receptor complex.barbiturate receptor complex.

• High lipid solubility, they enter the brain High lipid solubility, they enter the brain quickly, but they redistributed to other quickly, but they redistributed to other areas of the body, reducing their clinical areas of the body, reducing their clinical effect.effect.

Specific drugs compound (cont)Specific drugs compound (cont)

• They have good efficacy (70-80%) to They have good efficacy (70-80%) to terminate all type of seizure but with high terminate all type of seizure but with high rate of relapse due to short half-life.rate of relapse due to short half-life.

• Adverse effects respiratory suppression, Adverse effects respiratory suppression, hypotention, sedation, and local tissue hypotention, sedation, and local tissue irritation.irritation.

DiazepamDiazepam.. Half-life 15 minutesHalf-life 15 minutes

5-10 mg I.V., it can be repeated5-10 mg I.V., it can be repeated

Lorazepam.Lorazepam. Half-life 2-3 hours (less lipid soluble + bind more tight to Half-life 2-3 hours (less lipid soluble + bind more tight to

GABAergic receptor)GABAergic receptor)

Effect last for 6-12 hrsEffect last for 6-12 hrs

4-8 mg I.V.4-8 mg I.V.

MidazolamMidazolamMore lipid soluble than the other two, so shorter half life More lipid soluble than the other two, so shorter half life

with higher relapse.with higher relapse.

Good for continue I.V. infusion with titration accordingly.Good for continue I.V. infusion with titration accordingly.

0.2 mg /kg followed by 0.1- 0.2mg /kg/hr0.2 mg /kg followed by 0.1- 0.2mg /kg/hr

22 - -PhenytoinPhenytoin

• High lipid soluble with long durationHigh lipid soluble with long duration• Control 60-80%Control 60-80%• Non sedativeNon sedative• Cannot mixed with glucose, it Cannot mixed with glucose, it

precipitate out of solutionprecipitate out of solution• Loading dose 18-20 mg/Kg at rate not Loading dose 18-20 mg/Kg at rate not

exceed 50 mg/min; if no response, it exceed 50 mg/min; if no response, it can be repeated with half the dose.can be repeated with half the dose.

• Adverse effect : arrhythmia/ hypotentionAdverse effect : arrhythmia/ hypotention

IF NO RESPONSEIF NO RESPONSE, , Refractory status epilepticusRefractory status epilepticus Intensive Care Unit Intensive Care Unit

Consider potential incubation and Consider potential incubation and mechanical ventilation.mechanical ventilation.

Avoid the use of neuromuscular junction Avoid the use of neuromuscular junction blockade as it can mask ongoing motor blockade as it can mask ongoing motor manifestation. A short acting non- manifestation. A short acting non- depolarizing agent such as vecuronium is depolarizing agent such as vecuronium is preferred.preferred.

Drugs Therapy Cont.Drugs Therapy Cont...

3- Phenobarbital3- Phenobarbital

Dosage 15-30 mg/KgDosage 15-30 mg/Kg

Adverse side effectsAdverse side effects

-respiratory depression-respiratory depression

-hypotention-hypotention

-sedation-sedation

-cardiac depression-cardiac depression

4- Midazolam4- Midazolam

5- Propofol5- Propofol Anesthetic agentAnesthetic agentMechanism of action not knownMechanism of action not known3-5 mg/Kg followed by a continuous 3-5 mg/Kg followed by a continuous

1-18 mg/Kg/hr infusion1-18 mg/Kg/hr infusionSide effect:Side effect:

lacticacidosis, hypotention andlacticacidosis, hypotention andhypothermiahypothermia

IF NO RESPONSE IF NO RESPONSE Phenobarbitone or inhalational anesthesia Phenobarbitone or inhalational anesthesia

can be used to achieve can be used to achieve burstburst--suppressionsuppression

(Require continue EEG monitoring)(Require continue EEG monitoring)