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EPILEPSY:CLASSIFICATION, PATHOGENESIS
AND MANAGEMENT
DR AGABI OSIGWE P. MBBS(Benin), MWACP
SENIOR REGISTRAR NEUROLOGY UNIT.LAGOS UNIVERSITY TEACHING HOSPITAL.
6TH AUGUST,2013
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BIBLICAL REFERENCE
A man in the crowd answered, Teacher I
brought you my son, who is possessed by a
spirit that has robbed him of speech
,whenever it seizes him, it throws him to theground. He foams in the mouth, gnashes his
teeth and becomes rigid. I asked your disciples
to drive out the spirit but they could not. MARK 9(NIV)
6TH August,2013
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DEFINITION OF EPILEPSY
The occurrence oftwo or more unprovokedseizures
New: a disorder of the brain characterized by an enduring
predisposition to generate epileptic seizures
requires occurrence of at least 1 unprovoked seizure
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DEFINITION OF SEIZURES
Abnormal electrical discharge from a networkof neurons within the brain
Clinical features are determined by function of
brain region affected
Convulsive and non-convulsive seizures
Convulsive (jerky movements)
Non-convulsive (no jerky movements)
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CLASSIFICATION
Generalized and focal seizures Concept:
GS originate from neural networks in both
hemispheres
FS originate within networks limited to one
hemisphere
Classified as
Generalized seizures
Focal seizures
Unknown origin
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NPMCN UPDATE 2012
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EPILEPSY CME 2011
CLASSIFICATION ii
Tonic-clonic
Absence(typical; atypical;
absence with special features -
myoclonic absence, eyelid myoclonus)
Myoclonic(myoclonic;
myoclonic atonic; Myoclonic tonic
Clonic
Tonic
Atonic
Simple partial
Motor
Somatosensory
Psychic Autonomic
Complex partial
With automatisms Without automatisms
Secondary generalized
FOCAL (PARTIAL)GENERALIZED
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6TH August,2013 ILAE 2010 Revised terminology
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AETIOLOGY
Genetic
Directly resulting from a known or presumed
genetic defect(s) in which sz are core symptom
Structural / metabolic
Epilepsy due to a distinct dx associated with
substantially increased risk of epilepsy
Structural lesions may be inherited(e.g. tuberous
sclerosis)or acquired(e.g. stroke, trauma,infection)
Unknown cause
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PATHOGENESIS - concepts
Seizure initiation
Seizure propagation
Epileptogenesis
Genetics of epilepsy
Mechanism of action of AEDs
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SEIZURE INITIATION Hyperexcitability
The tendency of a neuron to discharge repetitively to astimulus that normally causes a single action potential
influx of extracellular calcium (Ca2+) causing prolonged
membrane depolarization
leads to opening of voltage-dependent sodium (Na+)channels, influx of Na, and generation of repetitive action
potentials
Followed by hyperpolarizing afterpotential (mediated by
GABA receptors or potassium (K+) channels
Hypersynchronization
the property of a population of neurons to discharge
together independently.
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SEIZURE PROPAGATION
Spread of activity is usually prevented by hyper-polarization
and surrounding inhibition (by inhibitory neurons)
However, high level activation (repetitive discharges) leads to
recruitment of surrounding neurons via several mechanisms:
Increased extracellular K+ (blunts hyperpolarization and depolarizesneighbouring neurons)
Accumulation of Ca2+ in presynaptic terminals (resulting in enhanced
neurotransmitter release)
Activation of NMDA excitatory amino acid receptors, causing Ca2+
influx and neuronal activation
Recruitment of neurons with loss of surrounding inhibition and
propagation of seizure activity into contiguous areas via local cortical
connections, and distally via long commisural pathways (e.g. corpus
callosum)
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Absence seizures
Normally, the thalamo-cortical circuits generate
oscillatory rhythms during sleep
This oscillatory behaviour involves interaction
between GABA B receptors (pacemakers), T-type Ca2+
channels, and K+
channels within the thalamus
Modulation of this interaction causes absence
seizures Activation of transient Ca channels (T channels) and
GABA B mediated hyperpolarization results in 3-4 Hz
oscillations
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MECHANISMS OF EPILEPTOGENESIS
Transformation of a normal neuronal network over time,into one that is chronically hyperexcitable.
Insult initiates a process that gradually lowers seizure
threshold in affected region, until spontaneous seizure occurs. Mechanism:
Structural changes in neural networks (e.g. in MTLE, selective loss of
inhibitory neurons to dentate gyrus; accompanied by reorganization
(sprouting) of surviving neurons, with change (increase) in excitability
Local hyperexcitability results in further structural changes over time,
until clinically evident seizures occur.
Also, functional (and metabolic) changes in receptor function occur
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MECHANISM OF AED Mainly block initiation or propagation of seizures
Via modification of ion channel or neurotransmitter function
Mechanisms
Inhibition of Na+-dependent action potential (phenytoin,
carbamazepine, lamotrigine, topiramate, zonisamide)
Inhibition of voltage-gated Ca2+ channels (phenytoin)
Decreased glutamate release (lamotrigine)
Potentiation of GABA receptor function (benzodiazepines
and barbiturates) Increased availability of GABA (valproic acid, gabapentin,
tiagabine)
Inhibition of T-type Ca2+ channels in thalamic neurons
(ethosuximide and valproic acid)
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MANAGEMENT
Differential diagnosis of epileptic seizures
Diagnosis
Clinical evaluation
investigations
Treatment
Pharmacological
Non-pharmacological
Surgical
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EPILEPSY CME 2011
DIFFERENTIAL DIAGNOSIS
Syncope (cardiac (e.g. arrhythmias; non-cardiac (e.g. vasovagal,
orthostatism)
Sleep disorders (narcolepsy, OSA, parasomnias)
Transient ischaemic attacks and transient global amnesia
Dizziness/vertigo
Paroxysmal (intermittent) movement disorders
Migraine (complex)
Metabolic (hypoglycaemia, alcohol) / delirium
Psychiatry base: panic/anxiety, conversion/psychogenic
seizures, dissociative states, malingering, hyperventilation, etc).
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EPILEPSY CME 2011
DIAGNOSIS i
History Careful and detailed
Eye-witness account valuable
Exclude differentials Risk factor evaluation
Seizure type: partial or generalized; type of
generalized or partial seizure Aura
Loss of consciousness (G) or impairment (CPS)
Sequence of events
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EPILEPSY CME 2011
DIAGNOSIS ii
Electroencephalography To identify electrical (potential) abnormalities
Ictal (during seizure) and interictal
Neuroimaging To identify structural lesions
MRI is superior to brain CT in seizure evaluation
Normal in idiopathic epilepsy
Abnormality is common in partial epilepsies e.g. TLE (hippocampal
sclerosis)
Blood tests
Baseline biochemical and haematologic parameters
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EPILEPSY CME 2011
EEG Normal
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EPILEPSY CME 2011
EEG Generalized spike and SW
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EEG Absence seizures
NPMCN UPDATE 2012
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EPILEPSY CME 2011
TREATMENT i
Early diagnosis and treatment improves long-term quality of life
Reduces morbidity and mortality
Early referral
Decision to treat
Patient and physician interaction in decision making
Explain pros and cons of treatment Offer treatment for epilepsy
Single seizures: consider risk of recurrence (abnormal neuro
exam, abnormal imaging, abnormal EEG)
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EPILEPSY CME 2011
TREATMENT ii
Choice of AED should be rational Monotherapy to maximal tolerable dose
Alternative monotherapy
Polytherapy (rational)
Use medications that are accessible to the patient on
the long-term
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EPILEPSY CME 2011
TREATMENT iii Important considerations
Treatment options
Pharmacological (first-line before second line)
Surgical (refractory seizures: resection, hemispherectomy,
vagus nerve stimulation)
Women of child-bearing age: folic acid 5mg daily
Comorbidities: mood disorders, medical illness
Treatment duration: 2 years initially (relapse 11-14%)
Psychosocial and cultural issues: driving, marriage,
employment, belief systems, cross-referrals
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EPILEPSY CME 2011
Table 1. Drug options for seizure treatment (NICE)
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EPILEPSY CME 2011
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TREATMENT iv
Improving adherence Patient and caregiver education
Reducing stigmatization
Simple medication regimes
Monotherapy and serial monotherapy
Controlled release formulations
Enhanced relationship between physician and
patient/caregiver
TREATMENT
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TREATMENT v