Seizure and Epilepsy

Learning objectives

 Analyze the definitions for Seizure and Epilepsy

 Apply seizure semiology into a clinical practice

 Analyze the classification of seizure and epilepsy

 Identify risk factors, provoking and precipitating factors of seizure

and epilepsy

 Demonstrate the approach to seizure and epilepsy

 Apply an appropriate investigation and treatment of seizure and

epilepsy
Seizure

a paroxysmal event
• due to abnormal, excessive, hyper synchronous discharges
• from an aggregate of CNS neurons
May not be observable objectively

5–10% of the population will have at least one seizure

Highest incidence
• early childhood and late adulthood
Cont…

Epilepsy
Recurrent seizures due to a chronic, underlying process.
• recurrent seizures due to correctable or avoidable conditions
not included

Epilepsy syndromes
• epilepsy with distinctive clinical and pathologic characteristics
• suggest a specific underlying etiology
ILAE-2017 Based Definition

 Seizures are transient events that include symptoms and/or signs of abnormal
excessive or hyper synchronous neuronal activity in the brain.
 A seizure is a sudden change in behavior caused by electrical hyper
synchronization of neuronal networks in the cerebral cortex.

 Epilepsy is the disorder of brain characterized by an enduring predisposition to

generate epileptic seizures, and by the
neurobiologic,cognitive,psychological,and social consequence of this
condition.

 The definition of epilepsy requires the occurrence of at least one epileptic

seizure.
Cont…

 Epileptic Seizure is a symptom of a disease but not a disease itself.

• A paroxysmal and transient event

• Due to an Abnormal Excessive or Hyper-synchronous electrical activity in

the brain

• Manifested by clinical symptoms/signs or electro-cerebral signs

• Epileptic seizure could be: provoked/unprovoked
 Epilepsy to be considered as a disease of brain than a symptom
 It is known that the risk of seizure recurrence after two unprovoked
seizures is greater than 60%.
 The summary risk for an additional unprovoked seizure following a first
unprovoked seizure is in the range of 40%.
 The summary risk for further unprovoked seizures approaches 60-80% in
those who have experienced two (or more) unprovoked seizures.
 Seizures clustering within 24 h confer approximately the same risk
for later seizures as does a single seizure.
 Epilepsy could be considered present if the unprovoked seizures
occurred at any time between age 1yr and age 80yr apart.
Unprovoked seizure

• Unprovoked seizure refers to a seizure of unknown etiology as well as

one that occurs in relation to a preexisting brain lesion or progressive
nervous system disorder.
• Unprovoked seizures that are determined to be due to an underlying
brain lesion or disorder are also referred to as remote symptomatic
seizures.
• They carry a higher risk of future epilepsy compared with acute
symptomatic seizures.
Cont…
The term “unprovoked” implies Recurrent reflex seizures
absence of a temporary or represents provoked
reversible factor lowering the
threshold and producing a
seizures that are defined as
seizure at that point in time. epilepsy.

Provoked seizure is when Acute symptomatic seizures:

induced by a transient factor
acting on an otherwise normal
brain to temporarily lower the  A seizure after a concussion
seizure threshold.  Seizure occur with fever
 Seizure in association with
 Reactive/Reflex seizure alcohol-withdrawal
 Acute symptomatic seizure.
The Causes of Epilepsy can Sometimes Overlap with the Causes of
Acute Symptomatic Seizures

ACUTE SYMPTOMATIC SEIZURE EPILEPSY

Provoked seizures Two or more unprovoked seizures 24

Situation specific seizures hours apart
Induced by an immediate underlying No provoking immediate medical
medical illness illness

The medical illness must affect the The medical illness must affect the
brain brain
Must happen at the time of the Can begin many years after an inciting
medical illness or be in closer time event

Treating the underlying cause is

enough Long period of AEDs is needed
No AEDs or Short term AEDs needed

Have Higher mortality Have Lower mortality

Acute symptomatic seizure

• Seizure within one week of stroke, traumatic brain injury, anoxic

encephalopathy, or intracranial surgery
• At first identification of subdural hematoma
• During the active phase of a central nervous system infection
• Within 24 hours of a severe metabolic derangement
• In population-based studies, acute symptomatic seizures make up 25
to 30 percent of first seizures.
ILAE DEFINITION OF EPILEPSY: Second Definition

A person with a single unprovoked seizure and with a risk of

approximately 60% or more of having a second seizure in the next 10
years:
Added in 2014 ILAE working group definition.
Emphasizes the importance of neuroimaging and EEG in the evaluation of
patients with a first-time seizure, as some of these patients will meet criteria
for epilepsy at the time of a first seizure.

• Examples include:
 Patients with a single seizure occurring at least a month after a stroke
 A single seizure conjoined with a structural or remote symptomatic etiology
 An abnormal epileptiform electroencephalography
 Family history of seizure
ILAE DEFINITION OF EPILEPSY: Third Definition

Epilepsy Syndromes even without Seizures:

• It is reasonable to consider children with Landau-

Kleffner syndrome to have epilepsy even without
clinical seizures

• Syndromes associated with persistent threshold

alteration can be made after the occurrence of a single
seizure.

• EEG features of Epileptic syndromes without clinical

seizure
 ILAE DEFINITION OF EPILEPSY
Individualized
determination of the
Resolved Epilepsy time at which this
definition is met, is
• A person who is seizure free required
for >10 years and off
medications for 5 years. Factors that should be
considered:
• Seems to be based on “expert
Age
opinion” and seems arbitrary.
Seizure type/s
• Still has an annual seizure
recurrence risk of 0.5% and Persistence or
1%: 10-20 fold increase than resolution of EEG
general population abnormalities.
Seizure Semiology

• Pre- Ictal: Events that occur immediately before the

seizure, and include Aura and Prodromal symptoms/signs

• Ictal semiology is the sign and symptoms observed during

and immediately after the seizure occurrence.

Motor; Sensory; Autonomic; Cognitive….

• Post-Ictal features: Features occur after the seizure stops

Ictal semiology: Elementary Motor features
Vesrsive activity and Posturing in Tonic Seizures
Ictal semiology: Elementary Motor Features
 Ictal semiology: Complex Motor
Features
 Automatisms are repetitive motor activities that are more or
less coordinated and resemble a voluntary movement but are
not purposeful.
 Automatisms usually occur in association with Impaired
Awareness and the individuals are usually amnesic to the ictal
feature.
 Could be Preservative automatism or De novo automatisms

Oro-alimentary automatism
Manual or pedal automatism
Gestural automatism

Manipulative automatism or Non-manipulative

Hyperkinetic automatism
Gelastic and dacrystic automatism
Ictal semiology: Automatisms
Classifications of Seizures and Epilepsy

• Purpose:

• Accurately identify the etiology of seizure or

epilepsy

• For initiation of treatment: Not all seizures and

epilepsies are treated

• Select appropriate workup and treatment modality

and drugs

• More than one type of seizure could exist at the

same time
Rules for Classifying Seizures: ILAE 2017
 ILAE 2017 Classifications of Epileptic Seizures

• Seizure classification starts with determination of the initial

manifestations of the seizure at onset.

• Focal seizures originate within a neuronal network limited to one

hemisphere that may be discretely localized or more widely
distributed.

• Generalized seizures originate at some point within the brain and

rapidly engage bilateral distributed networks.

• If the onset of the seizure is missed or is unclear, the seizure is of

unknown onset.
ILAE 2017 Classifications of Epileptic Seizures

• The second step in the classification of seizures is clarifying the

presence of impaired awareness.

• Awareness is defined as knowledge and understanding that

something is happening or exists.

• When a person is having a focal seizure, his or her awareness is

determined by whether the person knows who they are and what is going
on in his or her surroundings during the seizure
• It does not refer to awareness of the seizure occurring.

• Awareness is also distinct from responsiveness.

ILAE 2017 Classification of Seizure Types: Basic
Version

Unclassified: Due to inadequate information or

inability to place in other categories
ILAE 2017 Classification of Seizure Types:
Expanded Version
Rules for Classifying
Seizures: ILAE 2017
 Focal Motor Seizures
Motor onset Clinical descriptions
features
Motor seizures with increased tone or stiffening of the limb or
Tonic neck.
Irregular and non rhythmic fast and brief jerking of muscle
Myoclonic groups
Repeated, regularly spaced stereotypical jerking movements
Clonic
Atonic Sudden loss of tone in one body part
Epileptic Flexion of the waist and flexion or extension of the arms,
spasms usually in clusters
Coordinated but purposeless, repetitive motor activities that
Automatisms may appear normal in other circumstances.
 Focal Non-motor Seizure

Non motor Clinical Descriptions

Changes in heart rate, blood pressure, sweating,

Autonomic skin color, piloerection, or gastrointestinal sensations
Characterized by cessation of movement, which should be the
dominant feature throughout the entire seizure and not just a
Behavioral brief part of the seizure
arrest Clinical symptoms include a blank stare and cessation from
talking or moving

Changes in language function, thinking, or associated higher

cortical functions
Cognitive More specific examples include déjà vu, jamais vu or
hallucinations
Emotional Emotional changes such as dread, fear, anxiety, or pleasure.
Changes in sensory phenomena such as taste, smell, hearing,
Sensory vision, pain, numbness, or tingling.
 Focal Onset Seizure

• Focal seizures can be further classified as to whether they

evolve to a bilateral tonic-clonic seizure or not.

• Replaces secondary generalized tonic-clonic naming to

avoid any confusion between generalized and focal
seizures.

• These seizures start in one area of the brain (as with all
focal seizures) and then spread to both sides of the brain.

• This spread is typically clearly seen on EEG.

 Focal Onset Seizure Evolving to a Bilateral Tonic-Clonic
seizure

• Focal Onset Seizure Evolving to a Bilateral Tonic-Clonic seizure start as focal

aware or focal impaired awareness seizure.

• They manifest initially as focal motor or focal non motor feature before
progressing to bilateral tonic-clonic seizure.

Typical findings which differentiates focal from primary

generalized forms of seizures include:

Presence of Aura or Aura continua

Presence of post ictal Todd’s paralysis
Jacksonian march progression of focal motor activity
Asymmetric ictal activity
Presence of unilateral versive activity
 Generalized Seizures

• Generalized seizures originate at some point within the brain

and rapidly engage bilateral distributed networks.

• Patients will have impaired awareness or lose their

consciousness at the onset of the seizure.

• Similar to focal seizures, generalized seizures are classified

according to motor or non-motor manifestations occurring in
symmetric fashion.

• Broadly, motor seizures are either tonic-clonic or other

motor seizures.
• Non-motor generalized seizures primarily refer to absence
seizures.
 Generalized Seizures: GTCS

GTCS are dramatic, the best recognized and the most common forms.

Do not have an Aura, but they may be preceded by a prodrome—the vague

sense a seizure will occur—lasting up to several hours (PRE-ICTAL)

Seizure onset is abrupt, most often with loss of consciousness and a

generalized and often bilateral tonic contraction which immediately followed
by clonic phase (ICTAL)

The tonic phase includes an upward eye deviation with eyes half
open and the mouth open; ictal cry or moaning; cyanosis with
vibratory epileptic tonic spasms: Lasts for few seconds to minutes

The clonic phase showed the frequency of clonic jerks decreases, and
the amplitude may initially increase but later decreases just before
the Sz stops: Followed by flaccid limbs and sometimes incontinence

Confusion; exhausted; muscle ache; memory loss; headache….. (POST-ICTAL)

Unknown Onset Seizures and Unclassified Seizures

• If the onset of the seizure is missed or is unclear, the

seizure is of unknown onset.

• Seizures of unknown onset can be classified by:

• Motor: tonic-clonic or epileptic spasms

• Non-motor: behavior arrest

• If information is inadequate or if the seizure cannot be

categorized, then the seizure is considered unclassified.
 EXAMPLES

• A child has seizures with stiffening of the right arm and leg,
during which responsiveness and awareness are retained.

• Old = simple partial seizures

• New = focal aware tonic/motor seizures

 Cont…

• A 25 year old woman describes seizures beginning with 30 seconds

of an intense feeling that “familiar music is playing.”

• She can hear other people talking, but afterwards realizes that she
could not determine what they were saying.

• She didn’t fall down but wanders around the house

• After an episode, she is mildly confused, and has to “re-orient

herself.”

• Old = complex partial seizures

• New = focal auditory/sensory unaware seizures with automatism

 Cont…

• A woman awakens to find her husband having a seizure in

bed.

• The onset is not witnessed, but she is able to describe

unilateral limb stiffening followed by bilateral shaking.

• He is unresponsive during the episode

• Old = partial onset, secondarily generalized seizure

• New = focal tonic/motor to bilateral tonic-clonic seizure

 NEW CLASSIFICATION OF EPILEPSY SYNDROME

• The epilepsy syndrome is a new Epilepsy syndromes

addition to the current classification are grossly classified
system and is defined as “a cluster of as:
features incorporating seizure types,
EEG, and imaging features that tend to Idiopathic or Genetic
occur together. Generalized Epilepsy
Syndromes

• Factors that contribute to epilepsy Reflex Epilepsy

syndrome include age of onset, Syndromes
remission, triggers, diurnal variation,
intellectual and psychiatric dysfunction, Focal Epilepsy
EEG findings, imaging studies, family Syndromes
history, and genetics.
Epilepsy syndromes
Common Epilepsy Syndromes and EEG Findings
Etiologic Classifications of Epileptic Seizures

• Six etiologic categories have been defined:

• Structural Genetic
• Infectious Metabolic
• Immune Unknown
• When multiple potential etiologies are present,
priority should be given to the etiology with more
relevant management issues.
 Etiologic Classifications of Seizure: Based on age
Trauma; Genetic disorders; Infection; Brain tumor; Illicit
12-
drug use;
18
yrs
Unknown/Idiopathic
18-
Trauma; Alcohol withdrawal; Illicit drug use; Brain
35
tumor; Unknown
yrs Cerebro-vascular disease; Brain tumor; Alcohol
withdrawal

Metabolic disorders (uremia, hepatic failure,

> 35 electrolyte abnormalities, hypoglycemia,
yrs hyperglycemia)

Alzheimer's disease and other degenerative CNS

diseases
Idiopathic/Unknown
Some causes occur at any age: Metabolic, Trauma, CNS infection,
Unknown
Pathophysiology of Seizure and Epilepsy

• Mechanism of Epileptogenesis

• Transformation of a normal neuronal network into one

that is chronically hyper-excitable state.
• Mainly from remote or permanent neurologic injury

• Mechanism of Seizure Initiation

• Burst activity and hyper-syncronization of hyper-

excitable area

• Mechanism of Seizure Propagation

• Recruitment of surrounding neurons; long tracts and

fibers

• AEDs control seizures by acting on Sz initiation and propagation.

 Seizure Precipitants
• Some patients with epilepsy report seizure precipitants that
will not trigger seizures in unaffected individuals.

• More than 50% of subjects with epilepsy reported at least

one precipitant

• Emotional stress and Sleep deprivation were the most

common
• Nocturnal seizures: Seizures could occur only during
sleep
• Other precipitants were excessive fatigue, fever or
illness, flickering light, and menstruation.

• Drugs reduce threshold for seizure episode like TCAs,

tramadol, antibiotics, anti-histamines…..
• Breakthrough seizure occurs with missed AEDs dose
 DDX

• Syncope
• Transient ischemic attack (particularly in older adults)
• Migraine
• Panic attack and anxiety
• Psychogenic nonepileptic seizure
• Transient global amnesia (rare before the age of 50
years)
• Narcolepsy with cataplexy
• Paroxysmal movement disorders
 FEATURES SEIZURE SYNCOPE
Immediate PPT factors Usually none Emotional stress valsalva

Premonitory symptoms Usually aura; prodrome Tiredness; dizziness;

nausea
Posture at onset Variable Often erect
Transition to LOC Often immediate Gradual over seconds
Duration of LOC Minutes or more Seconds
Duration of convulsion Seconds to few minutes Not more than 15 seconds

Facial appearance at Cyanosis; frothing on Pallor

ictal mouth
Disorientation post Many minutes to hours Less than five minutes
event
Muscle aching post Frequent Sometimes
event
Tongue bite Common Rare
Headache Common Sometimes
Incontinence Sometimes Rare
True seizure vs. PNES
 Evaluation of First Onset Seizure

• ABC rule
• recognize and manage Life-threatening conditions
• History and P/E
No history of earlier seizures
(1)Confirm seizure
(2)determine the cause of the seizure
• risk factors
(3)decide whether anticonvulsant therapy is required
(4)treatment of underlying illness.
 Cont…

Goals of the history:

To characterize the event as a seizure,
 Rule out alternative diagnoses,
 Determine whether similar events have happened in the past, and
 Evaluate for underlying risk factors for seizures in the past medical history, family
history, and medications.

known history of epilepsy

(1) identification of the underlying cause
(2) precipitating factors
(3) adequacy of the patient's current therapy
 Cont…

• For focal seizures, some behaviors have localizing and/or lateralizing

value.
• For example, versive head turning or eye deviation to the left suggests
onset in the right frontal lobe,
• Unilateral sensory disturbance suggests contralateral parietal lobe
onset, and
• Prominent dysphasia suggests involvement of the dominant
hemisphere.
 Postictal period: typically
include confusion and
suppressed alertness.
 FND: may also be present,
often referred to as Todd
paralysis or postictal paresis,
aphasia, hemianopia, or
numbness.
 The postictal state may last
from seconds to minutes to
hours, depending upon
several factors.
 Alcohol intoxication or
withdrawal and drugs of
abuse should not be
overlooked as a potential
cause of seizure.
 Focal-onset seizures are less
likely to be drug-induced
Systematic
approach to
patients with
onset seizur
 Laboratory Studies

• Routine blood studies

• screen for toxins in blood and urine
• Serum Lactate,LDH,CPK,WBCs,Cortisol,
• Neuron specific enolase and serum Prolactin level within 2-6 hrs. of
seizure(GTCS VS PNES).
• lumbar puncture
• if there is any suspicion of meningitis or encephalitis
• in all patients infected with HIV, even in the absence of symptoms
or signs suggesting infection
 Brain Imaging
• Almost all patients with new-onset seizures
• MRI is superior to CT
• Seiure protocol MRI RECOMMENDED
 Electroencephalography (EEG)

• EEG is a graphic representation of voltage change on the brain cells over time.

• EEG is useful for epileptic seizures:

• Diagnosis of epileptic activity

• Classification of seizure and epilepsy
• Identify causes of epileptic seizures
• For selection and response to treatment
• Prognosis

• Continuous video EEG when compared with inter-ictal EEG.

 Electrophysiologic Studies

ICTAL-EEG
• Always abnormal during generalized tonic-clonic seizures
• Absence of EEG seizure activity does not exclude a seizure disorder
Inter-ectal EEG
• Cannot establish the diagnosis of epilepsy
If the New Onset Seizure is due to Epilepsy:
Consider Epilepsy Evaluation For Possible Causes
Treatment

• Treatment of underlying conditions

• Avoidance of precipitating factors
• Suppression of recurrent seizures
• antiepileptic medications or surgery
• Addressing psychological and social issues
Treatment of Underlying Conditions

• If due to metabolic disturbance or medications

• reverse the metabolic problem or avoid the drug
• antiepileptic drugs usually unnecessary
• Structural CNS lesion
• removal of the structural lesion (surgery, radiation, medical or
other therapies )
• antiepileptic medication for at least 1 year
Avoidance of Precipitating Factors

• Patients can identify particular situations that precipitate seizure

• sleep deprivation
• alcohol intake
• video game monitor,
• Music
• voice
• stress
 Evaluation of Recurrent Seizure on Treatment

• The main reasons for poor control of seizures are multi-factorial:

• Reassess for the diagnosis of seizure to be sure its truly an

epileptic activity

• Reclassify the type of epileptic activity and assess whether

the AEDs used are the right choice: Don’t forget multiple Sz.

• Assess in detail adequacy and proper choice of AEDs,

adherence for medication; for missed doses: Breakthrough
seizures

• Look for provoking factors like drugs; alcohol; sleep history

and others
 Breakthrough Seizures

• A breakthrough seizure is defined as one that occurs despite the

use of antiseizure medications that have otherwise successfully
prevented seizures in the patient in the past.

• DDx:

• Reflex epilepsies are those in which seizures are provoked

objectively and consistently by specific stimuli or activities in
patients who otherwise lack spontaneous seizures.

• Acute symptomatic seizures occur in patients with or without

epilepsy and are provoked at the time of an acute, and usually
severe, epileptic insult
 Breakthrough Seizures

Risk factors for Breakthrough

• Breakthrough seizures are Seizures include:
common:
Poor adherence
• A Ugandan study estimated
prevalence in a sample of 267 Suboptimal dose of
patients, of which 74% AEDs
experienced breakthrough
seizures. Antiseizure medication
instability and Interactions

• In an English sample of more Seizure Precipitants

than 2000 patients in a
prospective, observational trial, Proconvulsants drugs
the incidence of breakthrough
seizures was 37%.
 Antiepileptic Drug Therapy

• Mainstay of treatment for most patients with epilepsy

• Goal
• Completely prevent seizures without causing any side effects
• Preferably with a single medication
• Easy dosing schedule for the patient
• Choice of therapy is often determined more by the patient's specific
needs and S/Es
 When to Initiate?

• Recurrent seizures of unknown etiology

• Recurrent seizures of irreversible cause
• Single seizure with
1) An abnormal neurologic examination,
2) Presenting as status epilepticus
3) Postictal Todd's paralysis
4) Strong family history of seizures
5) Abnormal EEG
 Which drug ?

• Factors influencing the choice of an initial medication include

• The efficacy
• Convenience of dosing
• Potential side effects
• All of the commonly used antiepileptic drugs can cause similar, dose-related side
effects such as sedation, ataxia, and diplopia
• Absence, myoclonic, and atonic seizures or mixed
• Valproic acid
• Carbamazepine and phenytoin can worsen the above seizures
• Ethosuximide
• Effective for absence seizures
 Initiation and Monitoring

• Optimal dose is often a matter of trial and error

• Seizure frequency
• Side effects
• Start low go slow
• This process may take months or longer
• Increases in dose should be made only after achieving a steady state
with the previous dose
• i.e., after an interval of five or more half-lives.

• Mild sedation, changes in cognition, or imbalance resolve within a few

days
 Cont…

• What to Monitor?

• Clinical response

• Medication side effects and drug interactions

• Evaluation of Re-occurrence of a previously medical responsive seizure

• Identification of Drug resistant epilepsy

 Monitoring After Start of AEDs: Clinical response
Clinical response can be assessed by checking the frequency of
seizure occurred after treatment initiated.

ILAE defines seizure free or medically responsive epilepsy as

seizure freedom for 12 months or 3 times the longest previous
inter-seizure interval, whichever is longer: “Rule of three”

If no response titrate the first drug to maximum tolerable dose and

then add second alternative treatment and titrate similarly

If there is a response with the second drug, slowly taper the first drug
and withdraw slowly.

If there is no response with the second drug: RAP

Reevaluate the patient for adherence, drug dose and
interaction, provoking factors
Add a third drug
Perform EEG again
 Cont…

• If seizures continue despite the maximum tolerated dose and

documented compliance
• Switch to another antiepileptic drug
• Maintaining the patient on the first drug while a second drug is added
• Second drug adjusted
• First drug gradually withdrawn (usually over weeks)
 Monitoring After Start of AEDs: Side effects

• History of rash

• Avoid Lamotrigine

• Rash because of carbamazepine: Avoid also phenytoin and

phenobarb

• Use levetiracetam, gabapentin, pregabalin and valproate

• Weight gain and obesity

• Avoid valproic acid, gabapentin, pregabalin or carbamazepine

• Preferred to use topiramate and zonisamide

 Selective Issues: Comorbidities

• Some drugs are more likely to produce behavioral problems

• Others with mood-stabilizing properties might be helpful in patients

with concomitant psychiatric illness.

• Carbamazepine, lamotrigine, oxcarbazepine, and valproate can be

used in mood disorders

• Avoid levitracetam and phenobarbital

• In elderly preferable to titrate slowly and to lower target doses

specially protein bound AEDs
 Selective Issues: Women

• Ovulatory issues

• Avoid or reduce hepatic enzyme inducers; use newer AEDs

• Supplement Vitamin D and calcium
• Avoid valproate

• Pregnancy issues

• Avoid valproate and topiramate

• Use monotherapy
• Lamotrigine ???
• Supplement folic acid
• Phenobarb: Supplement vitamin K for mother and neonate
 Monitoring After Start of AEDs: Side effects

• Patients with renal insufficiency or who require dialysis often require lower
doses of renal excreted AEDs

• Post Dialysis dosing

• Avoid or reduce levetiracetam, gabapentin, and pregabalin.

• Those with reduced hepatic function may require lower doses of

medications that are hepatic metabolized.

• Avoid valproate and felbamate

• Reduce most AEDs

 Combination therapy

• Combination of drugs required in one-third of patients

• Focal epilepsy related to an underlying structural lesion
• Those with multiple seizure types
• Developmental delay
• Potential drug interactions should be recognized
• Myoclonic seizures resistant to Valproic acid
• Add clonazepam
• Nonresponsive absence seizures
• Add Valproic acid
• A third drug can be added if no response
Surgical Treatment of Refractory Epilepsy

• 20–30% of patients with epilepsy are resistant to medical therapy

• Surgery can be extremely effective

• Temporal lobectomy
• Lesionectomy
• Hemispherectomy or Multilobar resection
• Corpus callosotomy

• Not all medically refractory patients are suitable candidates for resective surgery
• Vagus nerve stimulation (VNS)
 When to Discontinue

• 70% of children and 60% of adults can eventually discontinue therapy

• Good patient profile for drug withdrawal
1. Complete medical control of seizures for 1–5 years
2. Single seizure type
3. Normal Neurologic examination
4. Normal EEG
5. If the epileptogenic cause is treated
• Attempt withdrawal of therapy after 2 years in a patient who meets all of the
above criteria
• Reduce the dose of the drug gradually over 4–6 months
• Most recurrences occur in the first 3 months
• Advised to avoid potentially dangerous situations during discontinuation
• Patient is motivated to stop
• Patient profile is assessed
 STATUS EPILEPTICUS

• It is a neurologic emergency.
• It can be convulsive or nonconvulsive.
• Convulsive status epilepticus is 5 minutes or more of
continuous seizure activity or two or more sequential
seizures without full recovery of consciousness between the
seizures.
• Nonconvulsive status epilepticus is a range of conditions in
which greater than 30 minutes of recurrent electrographic
seizure activity results in nonconvulsive clinical symptoms or
electrographic seizure activity persists for greater than 30
minutes in the absence of visible convulsion.
 Cont…

• Neurocritical Care Society is defined it as 5 minutes or longer of

continuous clinical and/or electrographic seizure activity or
recurrent seizure activity without recovery between seizures.

• Refractory status epilepticus: Clinical or electrographic seizures

that persist after adequate doses of an initial benzodiazepine
and an acceptable second-line antiseizure drug.

• Super-refractory status epilepticus: Seizures continue to recur

24hours or more after the onset of anesthetic therapy.
 Causes

• Anticonvulsant withdrawal or noncompliance

• Metabolic disturbances &electrolyte abnormalities
• Drug toxicity
• CNS infection
• CNS tumors
• Refractory epilepsy and head trauma
• Anoxic brain injury
• Alcohol withdrawal
• Traumatic brain injury
• Idiopathic
 Treatment

• The goal of treatment for convulsive status epilepticus is to achieve seizure control
as quickly and safely as possible.
• Initial steps should always be to stabilize the patient with special attention to
airway, breathing, and circulation.
• Admit the patient in the ICU or Neurocritical Care facility
• Administer oxygen and secure the airway as needed.
• Initiate ECG monitoring, perform finger-stick glucose, and screen for any
immediate life-threatening causes such as meningitis and intracranial mass lesions.
• Attempt IV access and send blood for electrolytes, hematology, and toxicology
screen.
• Emergent AEDs.
GUIDELINES FOR TREATMENT OF SE
 Catamenial Epilepsy

• Marked increase in seizure frequency around the time of

menses
• Some women
• Either the effects of estrogen and progesterone
• Changes in antiepileptic drug levels
Treatment
• Acetazolamide :started 7–10 days prior to the onset of
menses and continued until bleeding stops
• Increase in antiepileptic drug dosages during this time
• Control of the menstrual cycle
 Pregnancy

• Most women have an uncomplicated gestation and deliver a normal baby

• Seizure frequency during pregnancy
• Unchanged in ~50% of women
• Increase in 30%
• Decrease in 20%
• See patients at frequent intervals during pregnancy
• Monitor serum antiepileptic drug levels
• Incidence of fetal abnormalities in children born to mothers with epilepsy is 5–6%, compared to
2–3% in healthy women
• Teratogenic effects of antiepileptic drugs
• A syndrome comprising facial dysmorphism, cleft lip, cleft palate, cardiac defects, digital
hypoplasia, and nail dysplasia
• Risk increases with the number of medications used
 Cont…

• Pregnant women should be maintained on effective drug therapy

• Monotherapy at the lowest effective dose, especially during the first
trimester
• Patients should also take folate (1–4 mg/d)
• Mother should be treated with oral vitamin K (20 mg/d) in the last 2
weeks of pregnancy
• The infant should receive vitamin K (1 mg) at birth.
• Encouraged breast-feeding
Contraception

• Carbamazepine, phenytoin,
phenobarbital,
• Antagonize the effects of oral contraceptives
• Consider alternative forms of
contraception
Reference

Harrison’s Principles of Internal Medicine,20th edition

Bradley Clinical Neurology,8th edition,2021
Up-to-date online
Adams and victor’s Principles of Neurology 11th edition
• Continuum Neurology,2019
• 2017 ILAE Consensus Guideline