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Epilepsy
Southern Neurology
Classification of seizures 1
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Partial – arises from an epileptic focus , that is, a
localised region of the cerebral cortex in which
the excessive discharge of neurons occurs.
Partial seizures may be simple (consciousness
not impaired) – motor symptoms,
somatosensory symptoms, autonomic or psychic
symptoms; complex (with impairment of
consciousness) – may or may not have reactive
or stereotyped automatisms; or secondarily
generalised.
Classification of seizures 2
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Generalised – simultaneous involvement
of the whole cortex at the onset of the
seizure. That is, bilaterally symmetric and
without focal onset.
Subtypes include – absences and atypical
absences; myoclonic seizures, clonic
seizures; tonic seizures; and atonic
seizures
Epilepsy syndromes 1
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Partial epilepsy syndromes include –
idiopathic forms eg benign childhood
epilepsy with centro-temporal spikes;
childhood epilepsy with occipital
paroxysms and primary reading epilepsy;
symptomatic forms eg temporal, frontal,
parietal and occipital lobe epilepsies; and
cryptogenic. (Cryptogenic refers to
idiopathic partial but cause obscure).
Epilepsy syndromes 2
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Generalised subtypes include – benign neonatal
convulsions, childhood absence, juvenile
absence, juvenile myoclonic, epilepsy with
grand mal seizures on awakening; reflex
seizures
Generalised epilepsies can also be cryptogenic
or secondary (symptomatic) eg West syndrome
and Lennox-Gastaut syndrome.
Epidemiology of epilepsy
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Incidence of up to 100 per 100,000
population/year, while cumulative (life-time)
incidence of a non-febrile seizure is 2-5%.
Prevalence of active epilepsy 4-10/1000.
More than 50% of patients will experience a
recurrence after first seizure.
60-70% of patients taking anti-epileptic
medication will eventually become seizure free
(approx. 40% adults will experience relapse
after 2-years seizure freedom vs 20% of
children).
Clinical example
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A 6-year old girl has episodic staring spells of
sudden onset which are typically characterized
by a statue-like facial expression, cessation of
ongoing activity, unresponsiveness, eyeblinking and lip-smacking; the spell stops
abruptly and the child has no memory of the
event. EEG shows 3 Hz spike-and-wave
activity.
Clinical example (continued)
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Clinical diagnosis – childhood absence epilepsy.
Epidemiology – incidence 6-8/100,00 children
aged < 15 years; 10-12% of children with
epilepsy ages 5-14 years; F>M (3:2); family
history in 15-44%; 30-40% after age 7 years
develop generalised tonic-clonic seizures;
spontaneous remission in approximately 50%
(no GTCS 75% vs GTCS 35% seizure free).
Treatment – ethosuximide age < 6 years;
valproate age > 6 years or ethosuximide failure.
Tegretol, tiagabine and vigabatrin may
exacerbate absence seizures.
Partial seizures of frontal and
temporal origin
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>50% of partial seizures originate from the
temporal lobe.
Auras (or simple partial seizures) occur in
approximately 80% of patients with TLE. They
may be useful in localisation but not necessarily
reliable as ictal discharges may begin in a
clinically silent area but manifest as auras after
spreading to adjacent regions.
An aura typically lasts shorter duration than
period of altered consciousness (or complex
partial seizure) which may follow the aura.
Partial seizures (continued)
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Auras can be psychic/cognitive phenomena (eg
déjà vu jamais vu, dreamy state, fear, pleasure,
altered sense of reality, mind-body dissociation
or depersonalisation), speech phenomena (eg
dysphasia, speech arrest), illusions and
hallucinations (eg distortion of sizemacropsia/micropsia, shape, colour, distance,
olfactory and auditory hallucinations), and
autonomic phenomena (eg nausea, irregular
cardio-respiratory patterns, GI hypermotility,
chest discomfort).
Partial seizures (continued)
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Automatisms occur in 50-100% of temporal lobe
seizures and may occur in the ictal or post-ictal
phases. They typically appear during impaired
consciousness. They may be stereotyped (eg lip
smacking and chewing as seen with mesial
temporal involvement or tonic/dystonic as seen
with frontal lobe seizures) or reactive to
environmental stimuli (eg fumbling with clothing,
touching objects, looking around).
Post-ictal confusion, lethargy and/or aphasia
may occur and often can last up to 30 minutes
EEG in epilepsy
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An EEG cannot make or refute the diagnosis.
35% of patients with epilepsy show interictal
epileptiform activity in all routine waking EEGs,
15% do not show abnormalities even after
multiple EEGs and 50% show epileptiform
activity in some but not all recordings.
An EEG is of little help in predicting a
subsequent relapse although in children, an
active interictal EEG probably indicates an
increased risk of recurrence.
First-line treatment options –
which drugs?
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Carbamazepine
Valproate
Phenytoin
All three are effective in the treatment of
primary and secondarily generalised
seizures. In patients with mixed seizure
types eg myoclonic or absence, valproate
is the drug of choice.
First-line treatment options- for
how long?
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Minimum 2 years; range 2-5 years
seizure-freedom.
Studies have shown that about 70-80% of
all patients with epilepsy will eventually
become seizure-free and about half will
successfully withdraw their medication.
What rate of dose increments 1
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The usual recommendation is to slowly
adjust the drug dosage. For phenytoin and
carbamazepine, plasma concentrations
may help guide dose increments.
Typical doses for phenytoin –300-400 mg
once daily, carbamazepine – 200-600 mg
twice daily, valproate 500-1000 mg twice
daily.
What rate of dose increments 2?
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The commonest cause of failure of
carbamazepine therapy is non-compliance as a
result of unpleasant adverse effects (dizziness,
drowsiness, nausea, vomiting).
It is reasonable to start slow (eg 100-200 mg
twice daily) and increase by 100-200 mg/day
every 4-7 days until a final desired dose
(ranging from 600-1600 mg/day) is obtained.
Final dose depends in part on type and severity
of epilepsy
What constitutes optimal
treatment outcome
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Long-term seizure freedom is the ideal
treatment outcome.25-30% of patients will
continue to experience seizures despite optimal
therapy.
The principles of treatment are to prefer
monotherapy, and to titrate the dose of the
primary drug chosen until seizure freedom is
achieved in the absence of significant toxicity.
A major problem may be inadequate dosing due
to side-effects.
Discontinuation of treatment
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If seizure freedom has been achieved for 2-5 years,
treatment discontinuation is an option.
Seizure recurrence in adulthood is highest for JME (80%
recurrence) vs 40-50% for other subtypes.
75% of relapses occur within first 12 months, and at
least half of those relapses occur in the first three
months.
No driving during tapering. Tapering should occur over 610 weeks for all drugs except barbiturates and
benzodiazepines, which probably should be tapered
over 10-16 weeks.
When is a decision made to
change from a first-line agent ?
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If the first drug fails, particular attention should
be paid as to whether the diagnosis is correct,
whether there are triggering factors (eg sleep
deprivation, alcohol), and whether compliance is
an issue.
Assuming these are satisfactory, the
recommended approach is to commence
another appropriate drug and gradually withdraw
the initial agent. If the second agent also fails,
then combination therapy is recommended.
If seizure control is achieved, consider gradual
withdrawal of first agent.
What factors would determine
choice of adjunct therapy?
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Primary or generalised seizure disorder –
newer agents proven effective are
lamotrigine and topiramate.
Secondary or partial seizure disorder –
newer agents proven effective are
oxcarbazepine, lamotrigine, topiramate,
gabapentin, tiagabine, vigabatrin,
levetiracetam, pregabalin.
Characteristics making secondline agent the preferred option
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Efficacy – seizures are reduced by 25-50% in
50% of patients for newer AEDs. Partial seizures
are usually less effectively reduced in frequency
than generalised tonic-clonic seizures.
Tolerability
Once or twice daily dosing
No drug interactions – no significant hepatic
cytochrome P450 interactions, no adverse
additive side-effects with concurrent medications
Pregnancy/breast-feeding
How have the newer AEDs influenced the
management of epilepsy
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Patients have more treatment options than
previous. Studies would indicate that
seizure control should be better.
Patients are more likely to be on two
newer AEDS as combination rather than
mix of old and new.
? Patients are more likely to be offered
triple therapy than previous.
Case history
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55 y.o. male.
Presents after first complex partial and/or
secondarily generalised seizure. Patient
drove into the back of another vehicle.
Failed to stop an drove home.
Woke up in car outside his house and
found police attending scene. Accident
occurred 2 km from his house.
Case history (continued)
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CT brain normal, EEG –left temporal focus, MRI
left temporal atrophy.
Commenced tegretol 200 mg bd but ongoing
seizures and not tolerated well. Changed to
epilim 500 mg bd. Further CPS. Depressed as
both unable and too afraid to drive again.
Lamotrigine added – reports dizziness,
drowsiness, diplopia. Still having CPS. Wants
complete seizure freedom.
Changed to topiramate – no better. Changed to
trileptal –some improvement. Referred for
surgical consideration.
Carbamazepine (tegretol)
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First synthesized in 1953 as part of a programme
investigating analogues of chlorpromazine.
In an early study (Rodin et al 1974), carbamazepine or
placebo was administered to 37 chronically hospitalized
patients with intractable epilepsy and 44% of patients
given carbamazepine became seizure-free, 55% had
reduced ‘grand mal’ seizures and 83% had reduced
‘psychomotor’ attacks.
Comparison studies in the 1970 and 80s with phenytoin
showed similar efficacy (up to 80% of patients with newly
diagnosed epilepsy seizure free)
Carbamazepine (continued)
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Skin rashes occur in approximately 5% of patients.. If an
erythematous skin rash appears, treatment should
probably be stopped.
GIT –nausea, vomiting, diarrhoea (esp children 9-14%).
Neurological effects – nausea, dizziness, vertigo,
diplopia, headache, ataxia. Neuropsychological effects –
impaired memory, cognition and visual information
processing (?less if serum fluctuations are minimised).
Neutropenia – seen in 10-20% and usually transient. In
2%, it is more long-standing but may respond to dosage
reduction.
Water intoxication – usually asymptomatic. SIADH is
seen in –2% of patients.