EpilepsyEpilepsy

Dr.Ibrahim A

Introduction

Terms seizure and epilepsy are not synonymous

Seizure

A seizure is a paroxysmal event due to abnormal, excessive, hypersynchronous discharges from an aggregate of central nervous system (CNS)neurons (cortical neurons).

Epilepsy

Epilepsy describes a condition in which a person has recurrent seizures due to a chronic, underlying process.

Single seizure, or recurrent seizures due to correctable or avoidable circumstances, does not necessarily have epilepsy

Epilepsy

These are group of disorders of CNS, characterised by paroxysmal cerebral dysrhythmia, manifesting as brief episodes (seizures) of loss or disturbance of consiousness, with or without characteristic body movements (convulsions)

♦Epilepsy has a focal origin in the brain

EPIDEMIOLOGY

• The most common ages of incidence are under the age of 18 and over the age of 65.

• It has been estimated that about 1% of the population meets the diagnostic criteria for epilepsy at any given time, but some theorize that the prevalence may be much higher in fact.

5% of the population suffer a single sz at some time

0.5-1% of the population have recurrent sz = EPILEPSY

70% = well controlled with drugs (prolonged remissions); 30% epilepsy at least partially resistant to drug treatments = INTRACTABLE EPILEPSY.

Causes1. Primary( idiopathic) epilepsy:- Unknown genetic or biochemical

predisposition2. Secondary epilepsy:-a. Intracranial Tumor Cerebro -vascular disease Arteriovenous malformation Trauma ( birth injury, depressed

fracture, penetrating wound)

Infection ( meningitis, encephalitis)Congenital and hereditary disease (tuberous

sclerosis)b. Extra cranialMetabolicElectrolyteBiochemicalInborn errors of metabolismanoxia Hypoglycemia• Drugs• Drug withdrawal• Alcohol withdrawal

Causes

VITAMINESVascularInfectionTraumaAutoimmuneMetabolicIdiopathicNeoplasticS:pSychatric

FACTORS TRIGGER SEIZURE

Sleep deprivation Alcohol / withdrawal Physical / mental strain Flashing / flickering lights Infection Loud noise Hot water

Seizures are a result of a shift in the normal balance of excitation and inhibition within the CNS.

...... i.e. Abnormal discharges of neurons

That may be caused by any pathological process affecting brain>>>>

Types of Epilepsy

A. GENERALISED SEIZURES

i. Generalised tonic-clonic seizures

ii. Absence seizures

iii. Myoclonic seizures

iv. Atonic seizures

v. Infantile seizures (hypsarrhythmia)

Types of Epilepsy

B. PARTIAL SEIZURES

i. Simple partial seizures

ii. Complex partial seizures

iii. Secondary generalized seizures

Types of Epilepsy

B. UNCLASSIFIED SEIZURES

i. Unclassified seizures ii. Neonatal seizures iii. Infantile spasms

Partial

Synonymous with focal Activity is restricted to discrete areas of

cerebral cortex. Typically associated with structural

abnormalities of the brain.

Generalized

Involve difusse regions of the brain simultaneously in a bilaterally symetric fashion

May result from cellular, biochemical, or structural abnormalities that have a more widespread distribution.

Partial Seizures

Partial Seizures

Discrete regions of the brain. Consciousness is fully preserved during

the seizure (Simple-partial seizure) Consciousness is impaired (Complex

partial seizure) Partial seizure and then spread diffusely

throughout the cortex (partial seizure with secondary generalization)

Simple-Partial Seizure

Motor, sensory, autonomic, or psychic symptoms.

Without an obvious alteration in consciousness.

Three additional features

Three features

“Jacksonian march” abnormal motor movements may begin in a very restricted region, and gradually progress (over seconds to minutes).

May experience a localized paresis (todd`s paralysis) minutes to many hours.

Seizure may continue for hours or days. ”epilepsia partials continua”.

Simple partial. And Aura

Other forms of simple-partial seizures include those that cause changes in somatic sensation.

Some patients describe odd internal feelings. (fear, dejà vu)

When precede a complex-partial or secondarly generalized seizure, these simple partial seizures serve as a warning or aura.

Complex-Partial Seizures

Focal seizure activity Patient is unable to respond to visual or

verbal commands during the seizure and has impaired Consciousness or awareness of the ictal phase.

Frequently begin with an aura.

The start of the ictal phase is often a sudden behaivoral arrest or motionless stare.

Usually acompained by automatisms. The patient is typically confused following

the seizure.(seconds up to an hour).

Partial Seizures with Secondary Generalization

Partial seizures can spread to involve both cerebral hemispheres and produce a generalized seizur, usually of the tonic-clonic variety.

Is often difficult to distinguish from a primarilly generalized tonic-clonic seizure.

Careful history identifies a preceding aura.

Generalized Seizures

Generalized Seizure.

Practically defined as bilateral clinical and electrographic events without any detectable focal onset.

Arise from both cerebral hemispheres simultaneously

Generalized Seizures

Absence Seizure (Petit Mal) Atypical Absence Seizures Generalized, Tonic – Clonic Seizure

(Grand Mal) Atonic Seizure Mioclonic Seizure

Absence Seizures (Petit Mal)

Sudden brief lapses of consciousness without loss of postural control.

Typically last for only seconds, consiousness returns as suddenly as it was lost.

No postictal confusion

Absence seizures are usually accompained by subtle, bilateral motor signs (rapid blinking of the eyelids, chewing movements, or small clonic movements of the hands.

Can occur hundreds of times per day.

Always begin in childhood (ages 4 to 8) or early adolescence.

Hyperventilation tends to provoke.

Typical Absence seizure are not associated with other neurologic problems and respond well to treatment with specific anticonvulsants.

60 – 70 % will have a spontaneous remission during adolescence.

Atypical Absence Seizures:

– Lapse of consciousness is usually of longer duration.

– Less abrupt in onset and cessation– Accompained by more obvious motor signs.

Generalized Tonic – Clonic Seizures (Grand Mal)

The most common seizure type resulting from metabolic derangements.

The initial phase of the seizure is usually tonic contraction of muscles throughout the body.

After 10 to 20 s. The tonic phase of the seizure typically evolves into the clonic phase, produced by the superimposition of periods of muscle relaxion on the tonic muscle contraction.

Aura

A sensation perceived by a patient that precedes a condition affecting the brain.

An aura occurs before a seizure. It may consist of flashing lights, a gleam

of light, blurred vision, an odor , numbness, weakness, or difficulty in speaking.

Phases of grand-mal seizures Tonic phase:

• Contraction of muscle start

• Rigidity of arm

• Duration 15 sec

• Person loss consciousness and fall down

• Saliva merge from the mouth

• Tongue biting

• Sweating increase

Clonic phase

Arm and leg jerk rapidly After 30 sec or few minutes jerking slow

down and end Consciousness return slowly Eye rolled Show painful expressions Than person falls, unresponsive sleep for

15 minutes Than after awaking then sleep again for

hours

Clonic phase

The periods of relaxation progressively increase until the end of the ictal phase.

Usually last no more than 1 min.

Postictal phase is characterized by:– Unresponsiveness– Muscular flacciditidy – Excessive salivation– Bleadder or bowel incontinence

Patients gradually regain consciousness over minutes to hours

Tipically a period of postictal confusion.

Headache, fatigue, and muscle ache.

Atonic Seizure

Sudden loss of postural muscle tone lasting 1 to 2 s.

Consciousness is briefly impaired Usually no postictal confusion

Very brief seizure may cause only a quick head drop or nodding movement.

Longer seizure will cause the patient to collapse. (extremelly dangerous)

Myoclonic Seizure.

Sudden and brief muscle contraction that may involve one part of the body or the entire body.

Pathologic myoclonus is most commonly seen in association with metabolic disorders, degenerative CNS diseases, or anoxic brain injury.

Unclassified Seizures

Neonatal Seizure

Less than 1 month of age.

Brief episodes of apnea, eye deviation, eye blinking, or repetitive movements of the arms and legs.

Infantile Spasms

Infants under 12 months.

Abrupt movements of the head, trunk, or limbs.

The classic spasm is a sudden flexion of the neck and abdomen with extension of the limbs.

SEIZURE SYNDROMES

• There are many different epilepsy syndromes, each presenting with its own unique combination of seizure type, typical age of onset, EEG findings, treatment, and prognosis.

• Infantile spasms (West syndrome) is associated with brain development abnormalities, tuberous sclerosis, and perinatal insults to the brain. It affects infants, which by definition is between 30 days to 1 year of life.

• Generalized 3 Hz spike and wave discharges in EEG Childhood absence epilepsy affects children between the ages of 4 and 12 years of age. These patients have recurrent absence seizures that can occur hundreds of times a day.

• Benign focal epilepsy of childhood (Benign Rolandic epilepsy) begins in children between the ages of 4 and 13 years.

• Juvenile myoclonic epilepsy (JME) begins in patients aged 8 to 20 years.

• Temporal lobe epilepsy is the most common epilepsy of adults. In most cases, the epileptogenic region is found in the temporal structures (e.g., the hippocampus, amygdala, and parahippocampal gyrus). Seizures begin in late childhood and adolescence.

• Frontal lobe epilepsy • Lennox-Gastaut syndrome

Diferential Diagnosis

Syncope Psychological disorders Metabolic disturbances Migraine TIA Sleep disorders Movement disorders

Evaluation of the patient

Approach:

– History (from patient and witness)– Physical examination– Investigations– Treatment– Follow up

Three basic questions

1. Is it a seizure?– If so, what kind?

2. What caused it?3. What should be done?

History Event

– Localization– Temporal relationship– Factors– Nature– Associated features

Past medical history Developmental history Drug and immunization history Family history Social history

Physical Examination

General– esp. syndromal or non-syndromal

dysmorphic features, neurocutaneous features

Neurological Other system as indicated

– E.g. Febrile convulsion, infantile spasm

Laboratory studies

Electrolytes Glucose Ca Mg Liver and renal function test Urianalysis Toxicology screen Lumbar puncture

imaging

EEG CT MRI SPECT

Investigations

I. Exclusion of differentials:– Bedside: urinalysis– Haematological: CBP– Biochemical: U&Es, Calcium, glucose, ABGs– Radiological: CXR, CT head– Toxicological: screen– Microbiological: LP(Always used with justification)

II. Confirmation of epilepsy:– Dynamic investigations : result changes

with attacks• E.g. EEG

– Static investigations : result same between and during attacks

• E.g. Brain scan

Electroencephalography (EEG)

EEG indicated whenever epilepsy suspected

Uses of EEG in epilepsy– Diagnostic: support diagnosis, classify

seizure, localize focus, quantify– Prognostic: adjust anti-epileptic treatment

Electroencephalography (EEG)

Hemispheric or lobar asymmetries– Periodic (regular, recurring)– Background activity:

• Slow or fast• Focal or generalized

– Paroxysmal activity:• Epileptiform features – spikes, sharp waves• Interictal or ictal• Spontaneous or triggered

MANAGEMENT- IMMEDIATE

Air way Breathing Carry the person away from danger Put patient in recovery position

Treatment

AEDs Surgery

– Focal resection– hemispherectomy– Callosotomy (palliative)

Ketogenic Diet Brain Stimulation

Antiepileptic Drug

A drug which decreases the frequency and/or severity of seizures in people with epilepsy

Treats the symptom of seizures, not the underlying epileptic condition

Goal—maximize quality of life by minimizing seizures and adverse drug effects

Currently no “anti-epileptogenic” drugs available

Ideal Agent: If Exists

Ideal drug for treating SE– Rapid entry into CNS– Rapid onset of action– Long duration of action– Safety– Absence of sedation– Useful as maintenance AED

Classification of AEDs

Classical Phenytoin Phenobarbital Primidone Carbamazepine Ethosuximide Valproate (valproic

acid) Trimethadione (not

currently in use)

Newer Lamotrigine Felbamate Topiramate Gabapentin Tiagabine Vigabatrin Oxycarbazepine Levetiracetam Fosphenytoin

Partial SZ

Tonic clonic SZ

Absence SZ

Myoclonic & Atonic

1st Carbamazepine 2nd Valproic acid 1st Valproic acid 2nd Carbamazepine 1st Ethosuximide 2nd Valproic Acid 1stValproic acid 2nd Carbamazepine

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

and aplastic anemia in elderly patients, very rare & serious adverse. A mild, transient leukopenia in about 10% disappears in first 4 months of treatment ,impired balnnce ,rash , diplopia

Start100mg\12h then increase to 200mg\d upto max1000mg/12h

Phenobarbital 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:

but may produce excitement in some patients. Skin rashes

Tolerance and physical dependence possible.

Benzodiazapines (Diazapam and clonazapam)

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

Valproate (Valproic Acid) Enhances GABA transmission, blocks Na+

channels, activates K+ channels Absorption: 90% bound to plasma proteins Half-life: 6-16 hours Valproate side effects Aappetite increase &weight gain Liver failure Pancreatitis Rreversaible hair loss Odema Ataxia Teratogen_termor_tthrombocytopaenia Encephalopathy

Ethosuximide 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

Phenytoin 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.

Newer Drugs

Oxcarbazepine

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.

Lamotrigine

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,, phenytoin

Gabapentin

Add-on therapy for partial seizures, May interfere with GABA uptake Adverse effects: less CNS sedative effects than

classic AEDs

Levetiracetam

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

Avoid• DRIVING

• ASCENDING HEIGHTS

• WORKING WITH FIRE OR COOKING

• USING POWER TOOLS OR

• DANGEROUS ITEMS

• TAKING UNSUPERVISED BATHS

• SWIMMING

EFFECTS OF AEDs ON PREGNANCY

Teratogenicity(folic a 5mg) avoid valorate Breast feeding(except valorate-

carbamazep) Contraception non enzyme inducing AEDs

no effect

When star AEDs in pt with first SZ

• Presented with stutus epilepticus

• Abnormal EEG

• Abnormal nerological examination

• Strong family Hx of epielpsy

When we decrease the dose of AEDs

Normal CNS examination Normal EEG Normal IQ 2years free of SZ

Other Treatment Alternatives

Dietary treatment– Ketogenic diet– Modified Atkins diet

Surgical treatment– Vagal nerve stimulator– Surgical removal of seizure focus

DIET & OTHER TREATMENT

• Ketogenic diets may occasionally be effective in controlling some types of epilepsy.

• The mechanism behind the effect is not fully understood, shifting of pH towards a metabolic acidosis and alteration of brain metabolism may be involved.

• Ketogenic diets are high in fat and extremely low in carbohydrates, with intake of fluids often limited.

• Ketogenic diets are sometimes prescribed in severe cases where drugs have proven ineffective.

Ketogenic Diet

Traditionally started gradually in the hospital after a 24-48 hour fast– Families educated daily

Ratio (fat: carbs and protein)– 4:1 more strict– 3:1 for infants, adolescents

Calories 60-100% Fluids 85-100% Solid foods and/or formula Requires dietician support Strong family committment

• Ketogenic diet is not good for the heart or kidneys and medical problems resulting from the diet have been reported.

• The diet is extremely unpalatable and few patients are able to tolerate it for any length of time.

• Since a single potato chip is adequate to break the ketosis, staying on the diet requires either great willpower or perfect control of a person's dietary intake.

• People fed via gastrostomy or young children who receive all their food in the presence of a caregiver are better candidates.

Brain Stimulation for Epilepsy

Vagal Nerve Stimulation Transcranial Magnetic stimulation Intracranial stimulation

– Surface electrodes (‘responsive’) – Deep Brain Stimulation

• Hippocampus• Thalamus• Cerebellum

• Surgical treatment can be an option for epilepsy when an underlying brain abnormality, such as a benign tumor or an area of scar tissue (e.g. hippocampal sclerosis) can be identified.

• The abnormality must be removable by a neurosurgeon.

• Surgery is usually only offered to patients when their epilepsy has not been controlled by adequate attempts with multiple medications.

• The most common form of resective surgical treatment for epilepsy is to remove the front part of either the right or left temporal lobe.

• Palliative surgery for epilepsy is intended to reduce the frequency or severity of seizures.

• Hemispherectomy is a drastic operation in which most or all of one half of the cerebral cortex is removed.

• It is reserved for people suffering from the most catastrophic epilepsies, such as those due to Rasmussen syndrome.

Prolonged seizure activity lasting greater than 30 minutes

Or, recurrent seizures without the interval of recovery (consciousness) lasting greater than 30 minutes

Remember

Most seizures are brief, lasting less than 5 minutes

If a seizure is lasting greater than 10 minutes, are likely to be prolonged

Causes 1.stroke,including haemorrhagic - 20% 2.low AED levels (non compliace AEDs)

- 35% 3.alcohol withdrawal - 15% 4.anoxic brain injury - 15% 5.Metabolic disturbances - 15% 6.remote brain injury/congenital

malformations - 20%

7.infections - 5% 8.brain neoplasms - 5% 9.Idiopathic 5%

TreatmentStep 1

ABCDE– Maintain Airway- patient at risk for aspiration

– Breathing- place O2, be ready for intubation

– Circulation- obtain IV access– : check glucose levels if can not check give

50ml of D50 thiamine after take sample for RBG &

– Electrolytes: check electrolytes (Na, Ca, Mg, PO4), and anticonvulsent levels, toxiclogy screen ,RFT,LFT,RBG,

Treatment Step 2T:5min

Benzodiazepine Therapy– Diazepam– Lorazepam

Diazepam

Highly lipid soluble– Rapid CNS entry- stops seizures in 1-3 minutes

Rapid redistribution in fatty tissues– Brain concentrations fall quickly– Duration of action is 15-30 minutes– T1/2= 30 hr

Dose: <3yrs, 0.5mg/kg, >3yrs, 0.3mg/kg Side Effects: sedation, decreased respiration and

blood pressure

Lorazepam

Less lipid soluble than diazepam– Slower CNS, stops seizures in 6-10 min

Not as rapidly redistributed to fat stores– Longer duration of action 12-24 hr– T1/2 =14 hr

Dose: 0.05—0.1mg/kg NO rep within 2min Side Effects: decreased LOC, respiration and BP

T :10min

Treatment Step 3

T : 15minPhenytoin/Fosphenytoin

Phenytoin• IV dosing 20 mg/kg load• Stops seizures in 10-30 minutes• Duration of action 24 hrs, T ½=24hr• Max infusion rate of 1mg/kg/min, max- 50 mg/min• Side Effects: arrhythmias, hypotension, wide QT

interval, phelibitis• pH=11-12, may only give IV or po

Treatment Step 4

T : 20min Phenobarbital

– Lipid solubility < phenytoin– Duration of action>48 hrs, T1/2= 100 hours– Dose 20 mg/kg– Inert cath + I V fluid– Side Effects: sedation, decreased respiration

and BP– Be ready to intubate!!

TreatmentStep 5

Intubation & GA Propofol

Refractory Status Epilepticus

Status epilepticus that fails to respond to 2 AED.

Nearly 40% of status epilepticus are refractory!

Intubation, IV access Continuous EEG monitoring Medication Coma

– Pentobarbital |_Propofol– Midazolam _Very high dose phenobarb

– Midazolam– Propofol– Very high dose phenobarb

Malignant/super- refractory status epilepticus

Status epilepticus that does not respond to a course of anesthetic drug.

20% of refractory status epilepticus patients.

Needs combination therapy (AED & Anesthetic drugs) /immune therapy.

Consider the Etiology

LP: necessary for any febrile seizure under the age of 18 months– Must strongly consider in comatose patient –

please check imaging first– Remember SE can cause pleocytosis (usually

< 20 cells)– Do not delay antimicrobial therapy if CNS

infection is suspected– Consider acyclovir

SUMMARY

ABCDE Lorazepam (0.1mg/kg) or Diazepam

– Give 5 minute interval then may repeat

Fosphenytoin: 20mg/kg, may give additional 10mg/kg after initial load

Phenobarb: 20mg/kg- be ready for intubation If neurology not involved, call us General anasethesia (eg, propofol)

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