Epilepsy

Introduction
• Seizure: the clinical manifestation of an abnormal and excessive
excitation and synchronization of a population of cortical neurons
• Provoked seizure/acute symptomatic seizure → are due to an
acute condition such as a toxic or metabolic disturbance, head
trauma, or acute stroke
• Unprovoked seizure/remote symptomatic seizure → refers to a
seizure of unknown aetiology as well as one that occurs in relation
to a pre-existing brain lesion or progressive nervous system
disorder
• Epileptogenesis: sequence of events that converts a normal
neuronal network into a hyperexcitable network
• Definition of Epilepsy
• At least two unprovoked seizures occurring more than 24 hours apart
OR
• One unprovoked seizure and a probability of further seizures similar
to the general recurrence risk (at least 60%) after two unprovoked
seizures, occurring over the next 10 years
OR
• Diagnosis of an epilepsy syndrome
• Epilepsy is considered to be resolved if…
• an individual remained seizure-free for the last 10 years, with no
seizure medication for the last 5 years.

R. S. Fisher et al (2014) practical definition of epilepsy

Epidemiology
• Epilepsy affects 0.6% of the world population while < 0.5%
of east African population is affected
• There are two peaks of age when epilepsy occurs, 1st
childhood and adolescence and 2nd peak occurs in older
adults > 65 yrs
• Prevalence in high income countries range from 5 to 8 per
1000 population and 10 per 1000 in low income countries
• Incidence in high income countries 45 per 100000 population
and 82 per 100000 population in low and middle income
countries
Etiology of Seizures and Epilepsy
• Less than one-half of epilepsy cases have an
identifiable cause/provoked
• The remainder are idiopathic/unprovoked and genetic
• Infancy and childhood
• Prenatal or birth injury
• Inborn error of metabolism
• Congenital malformation
• Childhood and adolescence
• Idiopathic/genetic syndrome
• CNS infection
• Trauma
Etiology…
• Adolescence and young adult
• Head trauma
• Drug intoxication and withdrawal
• Older adult
• Stroke
• Brain tumor, brain abscess
• Acute metabolic disturbances
• Neurodegenerative
• Meningitis or encephalitis
Mechanisms

GABA Glutamate neurotransmitter

neuritransmitter→GABAa/GABAb
receptors→ Cl – influx/K+ →NMDA receptors→ open Ca+ and
outflux→hyperpolarization Na+ channels→
→inhibition depolarization→excitation
Mechanisms

neuritransmit GABA
↓
ter→
receptors→ GABAa/GABAb ↑Glutamate n
Cl
outflux→hyp – influx/K+ →NMDA rec
eurotransmit
ter
erpolarizatio eptors→ ope
n
→inhibition Na+ channels n Ca+ and
depolarizatio →
n→excitatio
n
Clinical diagnosis
• The diagnosis of epilepsy is mainly clinical.
• Obtain a clear history from the patient and an
eye-witnessed account of the episode
• Detail before the event
• Duration, number of events, regaining of
consciousness between events
• During an event (incontinence, tongue biting)
• What happened after an event (LOC, confusion)
• Ask about risk factors for epilepsy
• Physical exam- evidence for seizure (tongue
biting, evidence for injury, scars), neurological
exam(lateralizing signs)
True seizure vs pseudo seizure
Investigation
• Electroencephalogram (EEG)
• Useful in the diagnosis and classification of epilepsy.
• Useful if recorded during an epileptic attack, where the finding of
epileptiform activity (spikes and sharp waves) confirms the clinical
diagnosis
• Only about 50% of persons with proven epilepsy have an abnormal
first interictal EEG
• This percentage can be increased to around 85% with repeated
EEG testing, using provocation tests (hyperventilation and flashing
lights) and by doing sleep recordings.
• The finding of a normal interictal EEG therefore does not exclude
the diagnosis of epilepsy.
Normal EEG
Brain imaging
• Brain imaging with CT or MRI is helpful when a focal cause
of epilepsy is suspected, particularly in partial onset
epilepsies.
• This is even more so the case in epilepsies of later age
onset, 25 yrs or greater because of their likely focal onset.
• Brain imaging is expected to be normal in most generalized
onset epilepsies which occur in a mainly younger age group
e.g. teenagers.
• MRI scanning is more sensitive than CT,
Baseline investigations
• RFTs
• LFTs
• FBP
• HIV
• BLOOD GLUCOSE
• Prolactin level
• Lumbar puncture
ILAE classification of seizure and
epilepsy
Generalized tonic-clonic seizures
• Are bilateral and symmetric
generalized motor seizures,
that occur in an individual
with loss of consciousness.
• The tonic-clonic seizure
consists of a tonic (bilateral
increased tone, lasting
seconds to minutes) and
then a clonic (bilateral
sustained rhythmic jerking)
phase
Generalized tonic seizures
• Involves bilaterally increased tone of the limbs typically
lasting seconds to a minute.
• They often occur out of sleep and in runs of varying
intensity of tonic stiffening.
• The individual is unaware during these events.
• At the beginning of tonic seizures with more intense
stiffening
Generalized atonic seizures
• Involves sudden loss or
diminution of muscle tone
without apparent preceding
myoclonic or tonic features.
• Are very brief (<2 seconds)
and may involve the head,
trunk or limbs.
Generalized myoclonic
• A myoclonic seizure is a single or
series of jerks (brief muscle
contractions).
• Each jerk is typically milliseconds in
duration. Myoclonic status
epilepticus is characterized by
ongoing (> 30 minutes) irregular
jerking, often with partially
retained awareness.
• These two features distinguish a
myoclonic status epilepticus from
a generalized clonic seizure where
consciousness is lost and the jerking
is sustained and rhythmic.
generalized myoclonic atonic seizure
• A myoclonic-atonic seizure is
a myoclonic seizure followed
by an atonic seizure.
• Sometimes a series of
myoclonic jerks occurs prior
to the atonia. The head and
limbs are affected, typically
resulting in rapid fall.
• The myoclonic jerk may be
subtle.
Generalized epileptic spasm
• An epileptic spasm is a sudden
flexion, extension or mixed flexion-
extension of proximal and truncal
muscles
• lasting 1-2 seconds i.e. longer than a
myoclonic jerk (which lasts
milliseconds) but not as long as a tonic
seizure (which lasts > 2 seconds).
• Spasms typically occur in a series,
usually on wakening.
• Subtle forms may occur with only chin
movement, grimacing, or head nodding.
Absence seizure
• A typical absence seizure is
a generalized seizure with
abrupt onset and offset of
altered awareness
• Memory for events during
the seizures is usually
impaired
• Clonic movements of eyelids,
head, eyebrows, chin,
perioral or other facial parts
may occur
Atypical absence seizure
• An atypical absence seizure
has less abrupt onset and
offset of loss of awareness
than typical absence
seizures.
• They are often associated
with other features such as
loss of muscle tone of the
head, trunk or limbs and
subtle myoclonic jerks
Myoclonic absence seizure
• Rhythmic myoclonic jerks of
the shoulders and arms with
tonic abduction that results
in progressive lifting of the
arms during the seizure.
• The myoclonic jerks are
typically bilateral but may
be unilateral or asymmetric.
Perioral myoclonias and
rhythmic jerks of the head
and legs may occur
Absence with eyelid myoclonia
• Absence seizures accompanied
by brief, repetitive, often
rhythmic, fast myoclonic jerks
of the eyelids with
simultaneous upward deviation
of the eyeballs and extension
of the head.
• Seizures are typically very
brief (<6s in duration)
• Mostly awareness is retained
Focal aware seizures
• Awareness during a seizure
is defined as the patient
being fully aware of them
self and their environment
throughout the seizure,
even if immobile.
• If awareness is preserved,
the seizure is a focal aware
seizure
Focal unaware seizure
• Awareness during a seizure
is defined as the patient
being fully aware of
themselves and their
environment throughout the
seizure, even if immobile.
• If awareness is
impaired during the seizure,
the seizure is a focal
impaired awareness seizure.
Focal motor seizures
• A motor onset
seizure involves motor
activity (movement) and may
be due to either an increase
or decrease in contraction in
a muscle or group of
muscles.
• Depending on the muscle
groups involved and the way
they are affected
When to initiate anti-seizure drug ?
• Patients with 1st unprovoked seizure who have a normal or
nonspecific neuroimaging
• ↓ risk of seizure recurrence ( 21 – 45% at 2 yrs)
• Anti - seizure drug therapy deferred until after a second
unprovoked seizure.
• In patients with 1st unprovoked seizure who have CNS
abnormality on neuroimaging (such as a brain tumor or scar
tissue from an old head injury or CNS infection),
• The risk of seizure recurrence ≥ 60% over 10yrs ≈ to those with
two unprovoked seizures occurring >24 hours apart
• In this instance start treatment after the first unprovoked seizure.
Rx
• Immediate anti - seizure drug treatment reduces the risk of
seizure recurrence by about 35% over the next one to two
year, no impact on long term outcome and quality of life
• For adults presenting with second unprovoked seizure,
immediate anti - seizure drug treatment ↓ risk of seizure
recurrence by about 35% over the next 1 to 2yrs
• Acute symptomatic seizure →↓risk for subsequent epilepsy
compared with remote symptomatic seizures→ treated with
anti - seizure drugs in the acute setting
Choice of a drug – factors to consider
• Age (neonates, infants, and elderly people)
• Sex (issues related to contraception, childbearing potential, and bone
health)
• Presumed spectrum of activity against the individual’s seizure type or types
• Adverse effect profile, including age-related and sex-related side-eff ects
Drug interaction potential
• Expected effect of treatment options on any associated comorbidities
• Contraindications
• Dosing constraints (eg, need for slow titration, frequency of administration,
availability of convenient formulations)
• Cost and affordability
Optimising dose
• Aim at the lowest possible dose which is expected to control
seizures. If seizures persist or adverse effects develop,
adjust dose accordingly.
• The ILAE defined drug-resistant epilepsy as failure of
adequate trials of two tolerated,
Revising treatment when seizures are
not controlled
• Exclude non-adherence.
• Reassess diagnosis (is it epilepsy? Is the classification of
seizure types correct).
• Consider switching gradually to an alternative monotherapy
• Patients with difficult-to-control seizures might need early
combination therapy
• Give early consideration to alternative treatments, including
epilepsy surgery.
Management of epilepsy in pregnancy
• The use of antiepileptic drugs (AEDs) is associated
with increased baseline risk of fetal malformations
during pregnancy.
• Attempt to decrease pharmacological treatment to
monotherapy and utilize the lowest possible
effective dose of drugs that have shown minimal
risk of maternal and fetal neural tube defects
• S: lamotrigine (PO) 1-5mg/kg 12hourly for 4weeks
OR
• S: levetiracetam (PO) 10mg/kg 12hourly for 4weeks
AND
• A: folic acid (PO) 5mg 24hourly for 3-6months
Treating seizure free patient
• Consider gradual discontinuation of antiepileptic drug
therapy after at least 2 years of seizure freedom.
Surgical treatment
• Surgical treatment includes resection, destruction, or
disconnection of epileptic brain tissue, and neurostimulation,
which can be applied to various brain structures or to cranial
nerves to modulate cerebral networks generating seizures

• Surgical resection is offered to suitable candidates with

drug-resistant focal epilepsy
Neurostimulation
• Neurostimulation was mainly developed as a palliative
treatment for patients with drug-resistant epilepsy who are
not candidates for resective surgery.

• Approach
• Vagus nerve stimulation
• Brain responsive neurostimulation