Clinical Approach to Seizure And Epilepsy

Fatima Ismail, MBBS, FAAP

Assistant Professor of Neurology and

Developmental Medicine – CMHS
Adjunct Assistant Professor of Neurology
Johns Hopkins School of Medicine

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Disclosure
• No financial disclosure or conflict of interest pertaining to this lecture

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Outline
• Definitions
• How seizures develop
• Seizure semiology and classification
• Epilepsy and epilepsy syndromes
• Evaluation of a first time seizure
• Management of seizures and epilepsy
• Seizures in special population (pregnancy and children)

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 Definitions
• Seizure - The manifestation of an abnormal, excessive excitation and/or synchronization* of a
population of cortical neurons
• Manifestation will depend on:
• Age
• Area (circuits) involved
• Extension of involvement Avoid the term “seizure disorder"
• Spreading pattern
• Sleep-wake cycle

• Epilepsy – The condition of unprovoked seizures (two or more), usually in a person who has a
predisposition because of a chronic pathologic state (e.g. brain tumor, cerebral dysgenesis,
posttraumatic scar) or genetics.

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Definitions
• Epileptogenesis Sequence of events that converts a normal neuronal
network into a hyperexcitable network
• Epileptic Aura Subjective sensation or phenomenon that precedes or marks
the onset of the epileptic seizure ( sounds familiar?)

• Ictus The attack of seizure itself

• Post-ictal period The time after the ictus during which the patient maybe drowsy,
confused or disoriented
Adapted from Prof. Milos 2018 lecture

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How to think of seizures
• Where is it coming from?
• One hemisphere (R or L), both hemispheres
• Where does it start at?
• Which structures are involved at onset of ictal discharges
• How do the ictal discharges spread?
• Remain in one place, spread to the other hemisphere or are generalized at onset
• What causes the seizure?
• Cerebral lesion, metabolic disturbance, genetic,….
• Can it happen again?
• Provoked or unprovoked

Adapted from Prof. Milos 2018 lecture

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Abnormal neuronal firing
Paroxysmal
Depolarization Shift (PDS)

• Reflects epileptiform
discharge of a single
neuron

=Giant EPSP (excitatory

post synaptic potential)

• Prolonged
depolarization +
multiple action
potentials
Stafstrom C. Back to Basics: The Pathophysiology of Epileptic Seizures: A Primer For Pediatricians. Pediatrics in Review 1998

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Seizure onset and spread

• Focal area of hyperexcitability

• Spread locally (same hemisphere)
• Spread across (other hemisphere) 
focal to bilateral
• Spikes on EEG

• Primary Generalized seizures

• Begins simultaneously in both
hemispheres
• Interactions between cortex and thalamus
• Characteristic spike-wave activity on EEG

Stafstrom C. Back to Basics: The Pathophysiology of Epileptic Seizures: A Primer For Pediatricians. Pediatrics in Review 1998
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Excessive uncontrolled firing  excitotoxicity  cell death

Kaur et al., Antiepileptic drugs in development pipeline: A recent update eNeurologicalSci, 2016
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 1. Where seizures begin  (medication choice/surgery)
2. Level of awareness  Safety
Terminology 3. Motor or non-motor onset
Grand mal
Petite mal
Simple partial
Complex partial
Secondarily generalized tonic-clonic

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Name that seizure:
• Bilateral symmetric convulsive
movements (stiffening followed by
jerking) of all limbs with impairment
of consciousness
• Generalized at onset or unilateral to
bilateral
• Biting cheek/tongue
• Incontinence
• Post-ictal confusion, sleepiness and
amnesia
• Risk for acute kidney injury if
prolonged, why? Motor Tonic-clonic
Adapted from Prof. Milos 2018 lecture

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Name that seizure:
• Sudden, brief (“lightning-fast”)
movements that are not
associated with disturbance of
consciousness.
• These brief involuntary muscle
contractions may affect one or
several muscles
• Can be generalized or focal
• Impairment of consciousness
difficult to assess (seizures <1s)

Adapted from Prof. Milos 2018 lecture

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Name that seizure:
• Staring with
unresponsiveness
to external verbal
stimuli, sometimes
with eye blinking or
head nodding
• 3-20 seconds
• Sudden onset, rapid
resolution
• Age 4-14 years
• Seemingly normal
development and
intelligence

Adapted from Prof. Milos 2018 lecture

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Name that seizure:
• Clinical manifestations vary with site of
origin and degree of spread
• Consciousness, awareness or memory
impaired, begin slow, lasts 1-2 min
• Presence of aura (subjective sensation)
• Automatisms (stereotyped)

Focal onset with impaired awareness

Adapted from Prof. Milos 2018 lecture

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 Level of Awareness (affects safety during a seizure)
• Focal seizure - aware:
• Awareness remains intact, even if the person is unable to talk or respond during a
seizure. This replaces the term simple partial.
• Focal seizure - impaired awareness:
• If awareness is impaired or affected at any time during a seizure, even if a person has a
vague idea of what happened. This replaces the term complex partial seizure.
• Awareness unknown:
• Sometimes it’s not possible to know if a person is aware or not, for example if a person
lives alone or has seizures only at night.
• Generalized seizures:
• Awareness or consciousness affected

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Symptomatic (provoked) seizure
• Defined as a clinical seizure occurring at the time of a systemic insult or in close (1-2 weeks)
temporal association with a documented brain insult
• Causes:
• Structural: tumor, stroke(ischemia or hemorrhage), trauma, intracranial surgery, demyelination
• Infection: meningitis/encephalitis, abscess
• Acute/severe metabolic disturbances
• Drug or alcohol intoxication or withdrawal
• Medications that lower seizure threshold
• High fever (children) What is the cause of unprovoked seizures ?
• Severe sleep deprivation
• Treatment:
• Depends on the cause
• Correct underlying abnormality
• May require long term antiepileptic medications

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 From Seizure to Epilepsy (Unprovoked)
• Epilepsy = Two or more recurrent seizures unprovoked
by systemic or acute neurological insults

• Epilepsy Syndrome:
• a group of clinical characteristics that consistently
occur together, with similar seizure type(s), age of
onset, EEG findings, triggering factors, genetics,
natural history, prognosis, and response to
medications

• Refractory epilepsy = seizures not controlled by two or Framework for epilepsy classification
more appropriately chosen antiepileptic medications
Scheffer et al., Epilepsia, 58(4):512–521, 2017
or other therapies

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Temporal Lobe Epilepsy
• Mesial temporal (limbic)
 Associated with febrile seizures
 Affective, visceral or psychic aura
 Motor arrest or 'motionless stare'
 Automatisms, early impairment of consciousness
 Contralateral dystonic posturing or clonus
 MRI often shows mesial temporal sclerosis

• Lateral temporal
• Aura: often structured hallucinations: visual, auditory
• Consciousness may be preserved for longer time
• MRI may show structural lesion
Adapted from Prof. Milos 2018 lecture

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 Seizure type(s)
Age of onset
EEG findings
Triggering factors
Genetics
Natural history
Prognosis
response to medications

Stafstrom and Carmant , Cold Spring Harbor Laboratory Perspectives in Medicine, 2015

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From Seizure to Status Epilepticus
• Status epilepticus (tonic-clonic seizures):

• > 5 min of continuous seizures or electrographic seizure activity

or
• Two or more seizures with incomplete recovery of consciousness in between

• Uncontrolled tonic-clonic seizures > 30 minutes will have long term consequences

• Medical emergency (why?)

• Hypoxia, hypotension, acidosis, hyperthermia, rhabdomyolysis and neuronal
injury

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 Is it a seizure?
Evaluation of a First Seizure Focal or generalized onset ?
• Seizure focused history
• Pre-ictal: fever, head trauma, sleep deprivation, URI, vaccines, headache, Provoked or unprovoked?
aura, nausea/vomiting, sleepiness/lethargy
• Ictal: onset, spread, semiology, responsiveness, awareness, duration
• Post-ictal state: drowsiness, lethargy, post-ictal weakness or other focal Risk factors?
deficits , time to return to baseline

• Premorbid history
• Birth, development, history of febrile seizures, comorbid conditions like
cerebral palsy, developmental delay, recent stroke, CNS tumor, CNS
surgery

• Family history of seizures or other neurological disorders

• Medications: stimulant, toxins , ethanol withdrawal
• Life-style: sleep deprivation, stress
• Ask for a video of the event

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Evaluation of a First Seizure
• General Examination: determine an underlying condition
• Abnormal skin markings could indicate a neurocutaneous disorders
• Genetic/metabolic disorder: glaucoma, hepatosplenomehaly
• Head trauma

• Neurologic Examination: determine CNS abnormalities

• Focal neurological deficits
• Asymmetry in neurological examination
• Meningismus Focal findings mandate neuroimaging
• Papilledema
• Developmental delay/regression in children

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Differential Diagnosis
• Syncope
• Hypoglycemia
• TIAs
• Migraine with aura
• Non-epileptic seizures (formerly known as pseudo or psychogenic seizures)
• Breath holding spells (children)
• Parasomnias

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Evaluation of a First Seizure
• Look for triggers
• Blood test : glucose, electrolytes (Na, K, Ca, Mg, Phosphate), hepatic/renal function, CK,
+/- CBC
• Drug screen
• +/- Metabolic testing (neonates and children)

• Exclude life threatening causes

• CT/MRI : Structural lesions (hemorrhage)
• Lumbar puncture: if suspecting meningoencephalitis, after excluding brain herniation

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 EEG Treat the patient not the EEG

• Electrical activity from deep structures (thalamus, deep temporal lobe)

may not be recorded reliably by routine EEG

• Abnormal activity:
• Focal spikes or waves  focal epilepsy
• Diffuse bilateral spike waves  generalized epilepsy
• Types
• Routine EEG (hyperventilation/photic stimulation)
• Overnight EEG (sleep deprivation / capture states of consciousness)
• EEG/Video monitoring in epilepsy monitoring unit
• Intracranial EEG recording (surgical)
• EEG telemetry (Home monitoring) The first EMU at Tawam Hospital

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 Neuroimaging
• CT - acute setting to detect hemorrhage,
calcification, or tumors.

• MRI - sensitive for structural lesions: cortical

malformation, dysgenesis, or hippocampal sclerosis.

• MRI is more likely to show an abnormality in a

patient with focal seizures, abnormal neurologic
findings, or focal discharges on EEG

• New imaging techniques are available to aid in the

assessment of epilepsy for presurgical evaluation

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 Basic mechanism of anti-seizure (anti-epileptic) medications

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Rogawski , UC Davis
 Anti-Seizure (anti-epileptic) Medications
Goals of treatment • Patient characteristics
• Age
Seizure Control • Child bearing age
Minimize side effects • Comorbidities
Quality of Life • Contraindications
• Seizure type
• Focal epilepsy
Medication rules • Generalized epilepsy
Monotherapy • Status epilepticus
Start low and go slow
Monitor response • Medication side effects and drug-drug
Minimal effective dose interaction profile
Add a second medications • Cost
Switch to a different medication
Adapted from Prof. Milos 2018 lecture

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 Stabilize ABCDE
Time the seizure from its onset
Check glucose, if low give (Thiamine + Dextrose)
IV access + labs + toxicology screen

- IV Lorazepam
- IM Midazolam
- IV Diazepam
If not available
- Rectal Diazepam
- Intranasal Midazolam

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 IV fosphenytoin: monitor BP and ECG
IV levetiracetam
IV valproic acid: risk of respiratory depression (? Intubate)
If not available
IV phenobarbital

Continuous IV Midazolam, Pentobarbital, Propofol (intubate + continuous EEG)

Goal is to achieve burst suppression

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Management of Chronic epilepsy
• Life style modification
• sleep hygiene practices, avoid alcohol and
stimulants, stress reduction
• Medications
• Surgery (remove epileptogenic focus or
minimize spread)
• Others:
• Vagus Nerve Stimulation, Responsive
Nerve Stimulation, Ketogenic Diet

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 Complications

SUDEP = Sudden Unexpected Death in Epilepsy

Each year, about 1 in 1,000 adults and 1 in 4,500 children
with epilepsy die from SUDEP.

• Secondary to uncontrolled seizures

• Medications side effects
• Integral part of epilepsy pathology

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 Special populations: Pregnancy
• Effect of untreated seizures on mother and fetus (compliance)

• Effect of anti-seizure medications on fetus (highest in 1st trimester)

• Major congenital malformations: Neural tube, cardiac, Oral defects
• Neurodevelopmental outcomes of children

• Strategy:
• Plan ahead of pregnancy, start folate supplementation
• Switch to pregnancy safe option Avoid Safe
• Start with monotherapy with lowest effective dose Valproic Acid Levetiracetam
Phenobarbital Lamotrigine
• Monitor the dose and therapeutic levels
• Screen for fetal malformations

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 Special populations : Infants and children
• The very young brain is especially susceptible to
seizures

• Excitatory synaptic function develops before inhibitory

synaptic function  favoring enhanced excitation and
seizure generation

• Early in life, the neurotransmitter GABA causes excitation

rather than inhibition (Ben- Ari 2002; Pitka¨nen et al. 2015)

• Epilepsy in infants and children may have worst

cognitive and psychiatric comorbidities

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 https://www.epilepsydiagnosis.org

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Watch videos

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Focal onset seizures: From symptoms to localization
Clinical manifestations depend on the area of cortex involved

Sensory symptoms
Well localized, discriminatory, and spread relatively parietal lobe (primary somatosensory cortex, S1)
slowly (like a sort of ‘jacksonian march’)
Ill-defined, often accompanied by pain, spread within posterior insula-parietal operculum (supplementary
seconds somatosensory area, S2)
and may be contra-or ipsilateral
Gustatory aura insular region
Visual aura contralateral occipital cortex
Elementary auditory primary auditory cortex
Complex auditory Temproparietal junction
Olfactory aura) anterior mesiotemporal(uncinate)
Adapted from Prof. Milos 2018 lecture

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Focal onset seizures: From symptoms to localization
Psychic Manifestations
Déjà vu mesiotemporal without lateralization
Ictal fear Amygdala

Head and Limb Movements (motor)

Forced (versive) head turning contralateral frontal lobe
Nonversive head turning ipsilateral frontal & temporal lobe
Focal clonic movement contralateral frontal lobe
Hyperkinetic seizures frontal lobe

Eye and eyelid movements

Unilateral blinking ipsilateral temporal or frontal
Ictal nystagmus Contralateral frontal or occipital

Adapted from Prof. Milos 2018 lecture

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Focal onset seizures: From symptoms to localization

Dystonic posturing
Unilateral limb dystonia Contralateral temporal or frontal

Automatisms
Unilateral automatism Ipsilateral temporal or orbitofrontal
Postictal nose wiping Ipsilateral temporal
Rhythmic ictal non clonic hand movement Contralateral temporal lobe

Behavioral and phasic manifestations

Post ictal dysnomia Dominant hemisphere
Behavioral arrest Temporal, or orbitofrontal region

Adapted from Prof. Milos 2018 lecture

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Tonic Seizure