epilepsy npmcn 2013

7/29/2019 Epilepsy Npmcn 2013

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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

6TH August,2013


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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)

6TH August,2013


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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

6TH August,2013


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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

6TH August,2013


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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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EPILEPSY CME 2011

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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EPILEPSY CME 2011

TREATMENT v

epilepsy npmcn 2013

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