EPILEPSY DR. MANSOUR AL MOALLEM
Feb 08, 2016
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)