EPILEPSY
INTRODUCTION
• NEUROLOGICAL BASIS OF EPILEPSY
2
Main brain parts
Basic Science of epilepsy I 4
Basic Science of epilepsy I 5
March 2002 KSE teaching slide 6
Types of neurones
July 2008 Basic Science of epilepsy I 7
CNS Functions
• Motor
• Sensory
• Autonomic
• Psychic
Definition of Epilepsy
Epilepsy – derived from a Greek verb ‘epilembanein’
means ‘seize’, ‘capture’, ‘hold’ or ‘overwhelm by
surprise’
Defn: Chronic disorder of the brain characterized by
seizures which are :
❖Recurrent (two or more per year).
❖Spontaneous
❖Sudden in onset
❖Short in duration
❖Self limiting
R4S
Seizure definition
• Physiologically: Paroxysmal event due to abnormal ,
excessive, hypersynchronous discharge from an
aggregate of CNS neurons
• Clinically: Abnormal paroxysmal discharge of
cerebral neurons sufficient to cause clinically
detectable events noticeable to the patient, observer
or both - motor, sensory, autonomic or psychic
nature (Gastaut, 1973).
Seizure component : Prodromal, Aura, Ictal and Post-
ictal
Seizure manifestations
• May present as dramatic seizures but also has
milder forms
• Epilepsy can manifest with – motor, sensory,
autonomic, psychic - convulsions, brief
stares, odd sensations and smells, ALOC,
episodes of automatic behaviour
(automatisms)
• Nature of the seizures depend on part of the
brain affected
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Practical definitions
• Active epilepsy
> 2 or more seizures (24hrs apart) in <1 year.
• Serial seizures
Several attacks in one day but with complete
consciousness between attacks.
• Status Epilepticus
Continuous seizure activity lasting > 5 minutes.
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Epidemiology
Since antiquity epilepsy has been found in:
• Cosmopolitan
• Age groups
• Ethnic communities – all languages
• Races
• Social and economic classes,
• Both males and females
PREVALENCE
• About 10% of total world population
(780M) experiences at least one seizure
in normal life.
• But 80 million people have epilepsy
(recurrent seizures) globally
• 16 Million live in SSA.
PREVALENCE (CTD)
• Globally 8.2 per 1,000 of the
general population
• In the African region - range from
2.2 to 58 per 1000
⮚Lowest is in South Africa
⮚Higher in poor states (Cameroun)
In Kenyan studies :
• Kaamugusha and Feksi in 1988 (Nakuru) -
18.2
• AMREF (Kibwezi) -10.2
• Action AID (Kilifi) – 30
The prevalence rate in Kenya is 18 per
1000 population
Pathophysiology & Seizure
Mechanisms
• Seizures = excitation/inhibition imbalance
• Factors
Neuronal Glial Interstitial
• ↑excitation → start of abnormal
discharge
• ↓ inhibition → allows spread
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Neuronal (Intrinsic) Factors Modifying
Neuronal Excitability
⬧ Ion channel type, number, and distribution
⬧ Biochemical modification of receptors
⬧ Activation of second-messenger systems
⬧ Modulation of gene expression
(e.g., for receptor proteins)
Extra-Neuronal (Extrinsic) Factors
Modifying Neuronal Excitability
⬧ Changes in extracellular ion concentration
⬧ Remodeling of synapse location or
configuration by afferent input
⬧ Modulation of transmitter metabolism or
uptake by glial cells
Aetiology
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Aetiology of Seizures and Epilepsy
Infancy and childhood
• Birth injury
• Inborn error of metabolism
• Congenital malformation
Childhood and adolescence
• Idiopathic/genetic syndrome
• CNS infection
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Etiology of Seizures and Epilepsy
Adolescence and young adult
Head trauma
Drug intoxication and withdrawal*
Older adult
Stroke
Brain tumor
Acute metabolic disturbances*
HIV*
*Causes of symptomatic seizures but not necessarily epilepsy
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Relative Risks for Developing Epilepsy
Brain tumor
Family history 2.5
Simple febrile seizures 2
Alzheimer disease 7.5
SAH 34
Hemorrhagic stroke 26
Ischemic stroke 9.7
Bacterial meningitis 4.2
Encephalitis
16
Mild Brain Trauma
1.5
Moderate BrainTrauma
4
Severe Brain Trauma
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0 10 20 30 40
RR 1
Herman, Neurology 59:S21, 2002
Causes & Precipitants
of Seizures
• Inadequate sleep
• Low (less often, high) blood glucose
• Low sodium
• Low calcium
• Low magnesium
• Stimulant/other proconvulsant
intoxication
• Sedative and AED withdrawal
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SEIZURE SEMIOLOGY
SEIZURE SEMIOLOGY
Epilepsies classification
• Based on Aetiology &
Localisation
– Idiopathic
– Non-idiopathic (Symptomatic &
Cryptogenic)
Genetic/Structural/Immune/Metaboli
c/Infections/Unknown
– Focal or Generalised
• Based on age of onset
KSE & NECC teaching
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– Neonatal and Infantile
November 2014
slide
– Childhood
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Aetiology & Localisation
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Age Related Syndromes
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Common Age Related Epilepsies I
Neonatal Period Childhood
-Benign familial -Lennox – Gastaut
neonatal convulsions
syndrome
-Myoclonic epilepsy
(severe or benign) -Febrile convulsions
Infancy
-Myoclonic epilepsy
(severe or benign)
-West syndrome
33 November 2014
KSE & NECC teaching
34 November 2014
slide
Neonatal and Infantile
Genetic, Cryptogenic & Symptomatic (metabolic) syndromes
Self Limiting Syndromes Severe Syndromes
• Familial and neonatal • Early myclonic
seizures encephalopathy
• Febrile seizures • Ohtahara syndrome
• West
• Dravet syndrome
• Infantile severe myoclonic
epilepsy
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Early Childhood epilepsies
Genetic, Cryptogenic & Symptomatic syndromes
• Benign focal • Dravet's syndrome
Rolandic epilepsy • West syndrome
Occipital epilepsy • Juvenile myoclonic
• Childhood absence • Lennox-Gastaut syndrome
epilepsy
• Landau Kleffner syndrome
• Febrile seizures
• Progressive myoclonic
• Familial
• Rasmussen's encephalitis
Nocturnal Frontal lobe
epilepsy
Temporal lobe epilepsy
• Tuberous sclerosis
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Common Age related Epilepsies II
Adolescence Adulthood
Juvenile myoclonic Secondary
Juvenile absences and
Generalised tonic clonic symptomatic seizures
Familial Temporal lobe
Progressive myoclonic
Reflex epilepsies
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Epilepsy in the Elderly
Secondary & Symptomatic Epilepsies
Cerebrovascular disease Tumours
Neurodegenerative illness Trauma
Metabolic derangement Drugs
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Clinical classification of seizures
I Partial I I Generalised
⮚Simple ⮚Absence
⮚Complex ⮚Myoclonic
⮚Secondarily ⮚Clonic
generalised ⮚Tonic
⮚Atonic
III Unclassified ⮚Tonic clonic
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41 * KSE teaching slide
42 * KSE teaching slide
Partial seizures
(seizures beginning locally)
• Simple (Intact consciousness)
• Complex (Impaired consciousness)
• Partial with secondary generalisation
43
Simple partial seizures (consciousness not
impaired)
• With motor symptoms
• With somatosensory or special
sensory symptoms
• With autonomic symptoms
• With psychic symptoms
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Complex partial seizures (consciousness
impaired)
1. Simple partial then consciousness
impairment
a. without & b. with automatisms
2. Impaired consciousness at onset
a. without & b. with automatisms
3. Partial seizures (simple or complex),
secondarily generalized
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Generalised Seizures
• Absence
Typical & Atypical
• Myoclonic
• Clonic
• Atonic
• Tonic
• Tonic-clonic
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SEIZURE TYPES
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DIAGNOSIS
• History
• Physical Examination – CNS
• Basic Lab Investigations
• Roentgenography – XR, MRI
• Electrophysiological
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Diagnostic strategy
• History is the Mainstay of Diagnosis
• Is the event a seizure ?
• Is it epilepsy ? (is recurrence – likely or has
occurred)
• Are the seizures focal or generalised
• Do EEG + Clinical features define epilepsy
syndrome?
• Are Other tests necessary?
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Differential Diagnosis of Seizures
• NES
• Syncope • Migraine
• Panic attacks • Cerebral ischemia
• Night Terrors • Sleep disorder
• Movement • Metabolic
disorders disturbance
• Psychiatric
disturbance
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Differential Diagnosis
• NES
– Complex asynchronous movements,
– Hip thrusting, Head shaking,
– No LOC (injuries or incontinence)
• Syncope
– Movement clonic, myoclonic or dystonic
– Short-lived (<5sec)
– No injury, incontinence or confusion
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Management
of
Seizures & Epilepsy
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Nursing Aspects
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Grand mal seizures
Important Observations
● The ABCs
● Take note of the aura
● Position and movements of the head, body and
limbs
● Loss of consciousness
● Incontinence/Injuries e.g.. Tongue
● Time the length of each phase
● Onset of Status [recurrence or Prolonged duration]
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Grand mal seizures
Post ictal Care
● The ABCs
● Drain oropharyngeal secretions
● Place in recovery position
● Place an oral airway (if in Hospital)
● Continuous Observations
● Vital signs, Neurological assessment
● EKG and O2 monitoring
● Antiseizure treatment (rectal or IV)
55
Grand mal seizures
Post ictal Care
● Psychological Care:
● Alleviate Anxiety
● Reassure
● Re-orient the patient
● Stay with patient until fully recovered
● Obtain relevant history (Illnesses Injuries,
Drugs and compliance)
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Grand mal seizures
When to admit
● Any person having a first fit
● Any seizure last more than 10 min
● Serious injuries
● Prolonged Ictal & post ictal phase
● Serial seizures or Status epilepticus
● NB: A single seizure in a known person
with epilepsy may not merit admission
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1st Aid – GTCS summary.
Dos.
• Be calm.
• Move patient away from fire, traffic or water.
• Remove any harmful object near the patient.
• Loosen tight clothes, and remove glasses.
• Put something soft under the head.
• Turn patient on his or her side, so that saliva and mucus can
easily run out of the mouth.
• Remain with the patient until they regain consciousness.
Don’ts.
• Do not try to put anything in the mouth.
• Do not give anything to drink.
• Do not try to stop the jerking, or restrain the movements.
1st Aid : Complex partial seizure.
Appearance:
Blank stare, chewing, then random activity.
Person unaware and commands.
Duration 1-2 minutes 🡪 confusion and memory loss.
What to do:
Speak calmly and guide away from hazards.
Stay with the person until completely aware
Medical review if : 1st attack Pregnant
Injury Lasts more than 10min
What not to do:
Do not hold or restrain (unless in danger such as traffic).
Do not shout or expect verbal instruction to be obeyed
during or immediately following the seizure.
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MEDICAL MANAGEMENT
Management Preliminaries
Diagnosis Drug Treatment
? Genuine seizure Based on seizure type
? Partial onset Underlying or
? CNS pathology primary condition
? Systemic pathology
Prognosis
Classify the seizure
Epilepsy syndrome
Investigations Basic neural
Individualised pathology
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Starting Drug Treatment
❑ Counsel on realistictic likelihood of success
or failure
❑ Discuss possible outcome and expectations
❑ Discuss potential precipitants of fits
❑ Discuss lifestyle modification
❑ Discuss drugs side effects
❑ Discuss need for compliance
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General Facts About AEDs
• Good oral absorption and bioavailability
• Most metabolized in liver but some excreted unchanged in
kidneys
• Classic AEDs generally have more severe CNS sedation than
newer drugs (except ethosuximide)
• Because of overlapping mechanisms of action, best drug can
be chosen based on minimizing side effects in addition to
efficacy
• Add-on therapy is used when a single drug does not
completely control seizures
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
Current Pharmacotherapy
• Just under 60% of all people with epilepsy can
become seizure free with drug therapy
• In another 20% the seizures can be drastically
reduced
• ~ 20% epileptic patients, seizures are
refractory to currently available AEDs
Classification of AEDs
Classical Newer
• Phenytoin • Lamotrigine
• Felbamate
• Phenobarbital • Topiramate
• Primidone • Gabapentin
• Carbamazepine • Tiagabine
• Ethosuximide • Vigabatrin
• Oxycarbazepine
• Valproate (valproic acid) • Levetiracetam
• Trimethadione (not currently • Fosphenytoin
in use)
In general, the newer AEDs have less CNS sedating effects than the classical AEDs
Targets of drug therapy
1. Na+ Channel Blockers - OXC, CBZ, PHT, Zonisamide
2. Ca2+ channel Blocker - Ethosuximide
3. . K+ channel agonists - valproate and retiagabine
4. GABA Inhibitors – Gabapentine, Vigabatrin,
Benzodiazepines
5. Pleotropics - Felbamate, Lamotrigine, Topiramate
Valproate
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1. Na+ Channel Blockers
OXC, CBZ, PHT, Zonisamide
Reduce high frequency firing without
affecting physiological firing
2. Ca2+ channel Blocker
inhibit T-type (transient) Ca2+ currents
caused by the thalamus e.g. Ethosuximide
3. K+ channel agonists
• Decrease hyperexcitability in brain e.g valproate
and retiagabine
4. GABA INHIBITORS
• a. Gabapentine (Interfere with GABA re-uptake)
b.Vigabatrin (inhibit catabolic enzyme)
c.Benzodiazepines (increase frequency of GABA
mediated chloride channel opening)
d.Barbiturates (Prolong GABA-mediated chloride
opening)
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5. Pleotropics
❑ Felbamate,
❑ Lamotrigine
❑ Topiramate
❑ Valproate
M/A: among other:
✔ Modulate NMDA receptor via insensitive glycine
receptor
✔ Interfere with pathological glutamate
✔ Blocks voltage Na+ dependent channels
Choice of AED
❑Seizure type & Presumed
pathophysiology
❑Epilepsy syndrome
❑Pharmacokinetic profile
❑Interactions/other medical conditions
❑Efficacy
❑Expected adverse effects
❑Cost
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Management of 1 st Seizure
Diagnosis Treatment
Genuine seizure Based on seizure type
Partial onset Underlying or
CNS pathology primary condition
Systemic pathology
Prognosis
Classify the seizure
Epilepsy syndrome
Investigations Basic neural
Individualised pathology
72
Treat 1st Seizure ?
Risk of seizure recurrence
Increased risk
• Known symptomatic cause
• Partial seizure, esp. complex partial
• Family history of epilepsy
• Abnormal EEG (especially generalized spike-
and-wave pattern)
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Use of AEDs for 1st Seizure
Up to 60% ❑Presence of neurological
disease
may recur
❑Predictable epilepsies
Recurrence ❑Family history of epilepsy
rate reduced ❑Patient choices and
by AEDs vocational factors
Quality of life especially
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Targets of drug therapy
Na+ Channels
Phenytoin Carbamazepine Lamotrigine
Fosphenytoin Zonisamide
Ca++ Channels GABAA
Ethosuximide Benzodiazepines
Phenobarbitone
Primidone
GABA transporter GABA transaminase
Tiagabine Vigabatrin
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Choice of AED
❑ Seizure type & Presumed pathophysiology
❑ Epilepsy syndrome
❑ Pharmacokinetic profile
❑ Interactions/other medical conditions
❑ Efficacy
❑ Expected adverse effects
❑ Cost
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Drug Choice
Partial Seizures
Carbamazepine Felbamate Gabapentin
Phenytoin Topiramate Tiagabine
Valproate Lamotrigine Vigabatrin
Phenobarbital Levetiracetum
Primidone Oxcarbazepine
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Drug Choice
Generalised Seizures
❑ Absence ❑Tonic-clonic
Ethosuximide Valproate Phenytoin
Valproate Oxcarbazepine Felbamate
Carbamazepine Tiagabine
❑ Myoclonic
❑Lennox Gastaut
Valproate
Valproate Lamotrigine
Clonazepam Felbamate Topiramate
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Drug Therapy
❑ Monotherapy with a major drug up to
Maximum Tolerated Dose
Observe for 5-10 times the baseline
seizure interval
❑ Trial of 2nd major drug up to MTD
Increased efficacy in less than 20%
❑ Drug combinations
(Different mechanisms of action)
79
Outcome measures
• Seizures frequency
• Seizure severity
• Quality of life
• Cognitive development
• Interictal side effects
80
When to stop treatment
Risk of recurrence
Favourable
• Remitting epilepsy syndrome
• Single seizure (except myoclonic)
• Normal IQ
• Normal neurological findings
• Seizure-free period > 2 yr
• Age at seizure onset < 16 yr
81 *
When to stop treatment
Risk of recurrence
Unfavourable
• Unremitting epilepsy syndrome
• Multiple seizure types, myoclonic seizures
• Mental retardation
• Abnormal neurologic findings
• Seizure-free period < 2 yr
• Age at seizure onset > 16 yr
82 *
Treatment success rates
1 yr seizure-free
o Idiopathic generalized 82%
o Cryptogenic partial 45%
o Extratemporal partial 36%.
o Symptomatic partial 35%.
o Head injury and seizures 30%
o Cerebral dysgenesis 24%
o Temporal lobe 20%
o Hippocampal sclerosis 11%.
83 *
Adjunctive treatment
Lifestyle modification
Sleep Compliance
Stress reduction Diet
Abstinence
Alcohol
Drugs
84 *
Non drug treatment
Ketogenic diet 30%
Vagal stimulation <10%
Surgery 50%
Cell & Gene therapy Experimental
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PUBLIC HEALTH
PERSPECTIVES
OF EPILEPSY MANAGEMENT
86
Health burden
⮚Incidence c. 80a to 147b per 100,000/ yr
⮚Prevalence
Lifetime cumulative 5% - 9%
(2/3 develop epilepsy)
Point prevalence of 1.8%a - 0.47%c
⮚Highest in the young and in the elderly
87
Social Burden
• Epilepsy is associated with a lot of stigma
• Many communities in Kenya have different
myths and beliefs about epilepsy
• Many times these myths and beliefs portray
people with epilepsy as those who are
possessed by demons, have mental illness or
should be shunned
• This is not true!
88
Social Impact
General Personal
• Multifaceted and extensive • Stigma & Social Exclusion
• Poor Self Esteem
• Fits are Unpredictable
Dangerous, high risk of injury, • Poor Confidence
hospitalization and mortality • Poor Mental health
Anxiety / Depression
• Quality of life Cognitive impairment.
• Economic burden • Decreased Neurocognition
86% Indirect costs • Increased Co-morbidities
Fits Control reduces Medical & Surgical
costs
89
Economic burden of Epilepsy
90
Treatment gap
Currently 60 – 80% in RSC
Lower where there is :
• Better Access to health facilities
• Higher “physician” patient ratio
• Professional association for Epilepsy
• Postgraduate neurology training program
91
Aggravating Factors
• Poverty • High cost of treatment
• Illiteracy • Unavailability of AEDs
• Social stigma • Health care systems
• Misconceptions – Inefficient
surrounding the disease – Unevenly distributed
• Superstitious and • Political instability
cultural beliefs • Manpower shortage
• Discontinuation of
treatment
92
Suggested Solutions
• Educating the public
– Increasing awareness
– Stigma reduction
– Change health seeking behaviour
• Educating Health workers on Epilepsy
• Comprehensive epilepsy care
– From the community to the Tertiary Institution
• Advocacy for Policy changes
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