Seizures in Childhood

S
Sushan EkanayakeDoctor à Teaching Hospital - Kuliyapitiya, Sri Lanka
SEIZURES IN
CHILDHOOD
Dr. Sushan Ekanayake
Content
■ Definitions and Terminology
■ Neonatal Seizures
■ Mimickers of Epilepsy
■ Febrile Convulsions (Provoked Seizures)
■ Unprovoked Seizures
■ Seizure Classification
■ Emergency Management– Status Epilepticus
■ Mechanisms of Seizures
■ Pharmacology and Other Treatment Options
■ Take Home Message
 History
 Examination
 Investigations
 Management
 Education
 Follow-up
Terminology
■ Seizure
– A transient occurrence of signs and/or symptoms resulting
from abnormal excessive or synchronous neuronal activity in
the brain.
■ Acute symptomatic or provoked seizures
– occur secondary to an acute problem affecting brain
excitability, such as an electrolyte imbalance
■ Unprovoked seizure
– One that is not an acute symptomatic seizure.
■ Reflex seizures
– A type of seizure precipitated by a sensory stimulus.
Terminology (Continued…)
■ Epilepsy
– A disorder of the brain characterized by an enduring
predisposition to generate seizures and by the
neurobiological, cognitive, psychological, and social
consequences of this condition.
■ Seizure disorder
– A general term that is usually used to include any one of
several disorders, including epilepsy, febrile seizures,
and, possibly, single seizures and symptomatic seizures
secondary to metabolic, infectious, or other aetiologies
(e.g., hypocalcaemia, meningitis).
Terminology (Continued…)
■ Epileptic syndrome
– A disorder that manifests as one or more specific seizure
types and has a specific age of onset and a specific
prognosis.
■ Epileptic encephalopathy
– An epilepsy syndrome in which there is a severe EEG
abnormality that is thought to result in cognitive and
other impairments.
■ Epileptic disease:
– A pathological condition with single specific well defined
aetiology which is associated with epilepsy (e.g.
Terminology (Continued…)
■ Benign epilepsy syndrome:
– A syndrome characterized by epileptic seizures that are
easily treated or require no treatment and remit without
sequelae.
■ Reflex epilepsy syndrome:
– A syndrome in which all epileptic seizures are
precipitated by sensory stimuli
■ Focal seizures and syndromes:
– Replaces the partial seizures and localization related
syndromes elaborate (terms of simple partial and
complex partial epileptic seizures are no longer
recommended).
Terminology (Continued…)
■ Idiopathic epilepsy syndrome:
– A syndrome that is only epilepsy. No structural brain
lesion or any other neurological signs.
■ Symptomatic epilepsy syndrome:
– Syndrome in which seizures are due to identifiable
structural lesion in brain.
■ Probably symptomatic epilepsy syndrome:
– Syndromes that are believed to be symptomatic but no
aetiology identified.
What is a seizure?
■ A seizure is the manifestation of an abnormal,
paroxysmal discharge of a group of cortical
neurons. This discharge may produce subjective
symptoms or objective signs.
■ The key features of a seizure
– Paroxysmal nature of the event.
– Associated abnormal movements / subtle
phenomena.
– Altered responsiveness or impairment of
What is a convulsion?
■ Predominantly, an uncontrollable &
involuntary contraction/relaxation or spasm
of a group or groups of muscles.
Neonatal
Neonatal Seizures
■ Seizures occurring in 1st month of life.
■ There are five main neonatal seizure types:
– Subtle
– Clonic
– Tonic
– Spasms
– Myoclonic
Neonatal Seizures (Continued…)
■ Seizures Versus Jitteriness
– Jitteriness can be defined as
■ Rapid motor activities, such as a tremor or shake
■ That can be ended by flexion or holding the limb
■ Unlike most seizures, is usually induced by a stimulus
– Seizures,
■ generally do not end with tactile or motor
suppression
■ Often involve eye deviation and autonomic changes
Causes
Causes (Continued…)
Causes (Continued…)
Seizures in Childhood
Mimickers of Epilepsy
■ Paroxysmal events, abnormal movements / subtle
phenomena and states of altered responsiveness
are common in infants and children.
■ Diagnosing epilepsy in a non epileptic is more
harmful than missing the diagnosis in an epileptic.
■ The most useful diagnostic tool is an accurate
history taken from an eyewitness and/or patient
Mimickers of Epilepsy
(Continued…)
Mimickers of Epilepsy
(Continued…)
Mimickers of Epilepsy
(Continued…)
Breath-holding Attacks
Breath-holding Attacks
(Continued…)
■ Usually self limiting and no treatment is required.
■ Two types - blue and pallid.
■ Blue breath holding attacks
– Provoked by upsetting an infant.
– Episode starts with crying.
– Followed by breath holding and apnoea.
– Loss of consciousness may be associated with a few
clonic jerks and bradycardia.
– May occur repeatedly or sporadically.
– Usually occur after 6 months of age with a peak
Breath-holding Attacks
(Continued…)
■ Pallid breath holding attacks
– Provoked by upsetting an infant.
– Crying prior to episode may not be apparent.
– Become pale and bradycardic.
– Loss of consciousness may be associated with tonic
jerks.
– Usually occur after 6 months of age with a peak
incidence at 2 years.
Syncope, Migraine, Benign
Paroxysmal Vertigo
Few Other Causes
Pseudo-seizures
■ Pseudo seizure is the second most common cause
of misdiagnosis.
■ Pseudo seizures could occur when there is a history
of epilepsy / family history of epilepsy or even
concurrent with epilepsy.
■ The difficulty arises when epilepsy coexists.
Pseudo-seizures (Continued…)
Reflex Seizures (Stimulus-
Precipitated Seizures)
■ Many patients with epilepsy can identify
precipitating or provoking events that predispose
them to having a seizure.
■ There is another group of patients who have
seizures in response to a specifically identifiable
sensory stimulus or activity and are considered to
have reflex seizures.
■ Because no known reflex may be involved, more
appropriate terms may be sensory-precipitated or
Reflex Seizures (Stimulus-
Precipitated Seizures)
(Continued..)■ Stimuli may be
– external (light, patterns, music, brushing teeth)
– internal (math, reading, thinking, self-induced)
■ Reflex seizures may be
– generalized
– Partial
– non-convulsive
– Absence
– myoclonic
Reflex Seizures (Stimulus-
Precipitated Seizures)
(Continued..)
■ avoidance or modification of stimuli is the initial
approach.
■ Such activities may include
– wearing blue or polarized sunglasses
– avoiding high-contrast flashing-light video
games
– using a TV remote control or watching TV in a
well-lit room at a distance of > 8 feet
– covering one eye when in a provocative
Reflex Seizures (Stimulus-
Precipitated Seizures)
(Continued..)
Generalized Seizures vs Mimickers
Generalized Seizures vs
Mimickers(Ctd…)
Provoked Seizures
■ Febrile seizures
■ Metabolic
– Hypoglycaemia
– Hypocalcaemia/hypomagnesaemia
– Hypo/hypernatraemia
■ Head trauma
■ Meningitis/encephalitis
■ Poisons/toxins.
Seizures in Childhood
Febrile Seizures
■ Febrile seizures are seizures that
– occur between the ages of 6 and 60 months (peak 12-18
months)
– with a temperature of 38°C (100.4°F) or higher
– that are not the result of CNS infection or any metabolic
imbalance
– occur in the absence of a history of prior afebrile
seizures.
Febrile Seizures (Continued…)
■ An epileptic seizure occurring in childhood,
– after age 1 month
– associated with a febrile illness
– not caused by an infection of the central nervous system
(CNS)
– without previous neonatal seizures or a previous
unprovoked seizure
– not meeting criteria for other acute symptomatic
Febrile Seizures (Continued…)
■ Simple febrile seizure
– is a primary generalized
– usually tonic-clonic
– attack associated with fever
– lasting for a maximum of 15 min
– not recurrent within a 24-hr period
Febrile Seizures (Continued…)
■ Complex febrile seizure
– is more prolonged (>15 min)
– and/or is focal
– and/or recurs within 24 hr
■ Febrile status epilepticus is a febrile seizure lasting
longer than 30 min.
Febrile Seizures (Continued…)
■ Most patients with simple febrile seizures
have a very short post-ictal state and usually
return to their baseline normal behaviour and
consciousness within minutes of the seizure.
Febrile Seizures (Continued…)
■ Febrile infection–related (or refractory ) epilepsy
(FIRES)
– is a very different disorder
– seen predominantly in older (>5 yr) usually male
children
– associated with an encephalitis-like illness
– but without an identifiable infectious agent
■ Children with FIRES were previously normal but
subsequently develop difficult-to-treat epilepsy.
Febrile Seizures (Continued…)
■ A few epilepsy syndromes typically start with febrile
seizures
■ These are,
– Generalized epilepsy with febrile seizures plus
(GEFS+)
■ Autosomal dominant syndrome
■ Onset is usually in early childhood, and remission is
usually in mid-childhood
■ Characterized by multiple febrile seizures and by
Febrile Seizures (Continued…)
– Severe myoclonic epilepsy of infancy (SMEI or
Dravet syndrome )
■ Most severe of the phenotypic spectrum of febrile
seizure–associated epilepsies.
■ Initially characterized by febrile and afebrile unilateral
clonic seizures that recur every 1 or 2 mo.
■ Seizures subsequently start to occur with lower fevers
and then without fever.
■ During the second year of life, myoclonus, atypical
absences, and focal seizures occur frequently and
developmental delay usually follows.
– Temporal lobe epilepsy secondary to mesial
temporal sclerosis
Febrile Seizures (Continued…)
■ Epidemiology
– Between 2% and 5% of neurologically healthy infants and
children experience at least one, usually simple, febrile
seizure
– Febrile seizures recur in,
■ approximately 30% of those experiencing a first
episode
■ in 50% after two or more episodes
■ in 50% of infants younger than 1 year of age at febrile
seizure onset
– Approximately 15% of children with epilepsy have had
febrile seizures
Febrile Seizures (Continued…)
■ Risk Factors for seizure recurrence
– Having no risk factors carries a recurrence risk
of approximately 12%; one risk factor, 25–50%;
– two risk factors, 50–59%; three or more risk
factors, 73–100%.
Febrile Seizures (Continued…)
■ Risk Factors for Occurrence of Subsequent Epilepsy After a
Febrile Seizure
Febrile Seizures (Continued…)
■ Evaluation
Febrile Seizures (Continued…)
Febrile Seizures (Continued…)
Febrile Seizures (Continued…)
■ Indications for admission to hospital after a febrile
seizure
– First febrile seizure.
– Age <18 months.
– Incomplete recovery after one hour.
– Any likelihood of CNS infection.
– A ‘complex’ febrile seizure.
– Fever has lasted more than 48 hours before
onset of seizures.
– Home circumstances inadequate/excessive
parental anxiety/parents’ inability to cope.
Febrile Seizures (Continued…)
■ Investigations
– Blood studies (SE, Ca2+, phosphorus, Mg2+,
FBC) are not routinely recommended in the
workup of a child with a first simple febrile
seizure.
– If clinically indicated (e.g., dehydration), SE
should be performed. A low sodium level is
associated with a higher risk of recurrence of the
febrile seizure within the following 24 hr.
– CBS should be done
Febrile Seizures (Continued…)
■ Investigations (Continued…)
– Lumbar puncture should be performed
■ for all infants younger than 6 months of age
■ if the child is ill-appearing
■ at any age if there are clinical signs or symptoms of
concern
■ is an option in children who have been pre-treated
with antibiotics
■ is an option in a child 6-12 months of age who is
deficient in Haemophilus influenzae type b and
Streptococcus pneumoniae immunizations or for
whom the immunization status is unknown
Febrile Seizures (Continued…)
■ Investigations (Continued…)
– EEG
■ If the child is presenting with the first simple febrile
seizure and is otherwise neurologically healthy, an
EEG need not be performed
■ An EEG would not predict the future recurrence of
febrile seizures or epilepsy
■ EEGs performed within 2 weeks of a febrile seizure
often have nonspecific slowing, usually posteriorly.
Thus if an EEG is indicated, it is delayed until or
repeated after more than 2 weeks have passed.
■ An EEG should generally be restricted to special cases
in which epilepsy is highly suspected
Febrile Seizures (Continued…)
■ Investigations (Continued…)
– A CT or MRI is not recommended in evaluating
the child after a first simple febrile seizure
– The workup of children with complex febrile
seizures needs to be individualized
Febrile Seizures (Continued…)
■ Management
– Fever
– Acute Event (Will be discussed later)
– Prophylaxis
– Follow-up
Febrile Seizures (Continued…)
■ Management of Fever
– The fever should be treated to promote the
child’s comfort.
– An adequate fluid intake should be ensured to
prevent dehydration.
– Physical methods to reduce the body
temperature, such as fanning, and light clothing,
can be used
– Paracetamol and ibuprofen (if not suspecting
Dengue) are the recommended antipyretics.
– Should be prescribed in correct dose
Febrile Seizures (Continued…)
■ Management – Prophylaxis
– Long-term prophylaxis
■ Phenobarbitone - frequent and substantial side effects.
■ Sodium valproate - as effective as phenobarbitone, but may
produce fatal hepatic or pancreatic dysfunction in this age group.
– Intermittent prophylaxis
■ Oral or rectal diazepam
– As soon as the child starts fitting.
– Whenever the child is febrile and before the child starts fitting.
■ Oral clobazam
– Issues
■ recurrence is most likely when the fever has been present for less
than one hour.
■ Child will become drowsy – will affect clinical judgment
Febrile Seizures (Continued…)
■ Management – Evidence based Facts
Management of simple febrile seizures Sri Lanka Journal of Child
Health, 2017
Current Practice
Management of simple febrile seizures
Dr. Jithangi Wanigasinghe
Consultant Paediatric Neurologist
Febrile Seizures (Continued…)
■ Management – Follow up
– No need of routine follow up generally
– Specific cases should be assessed individually
and followed up as necessary
– If on long term prophylaxis – follow up to assess
drug side effects
Febrile Seizures (Continued…)
■ Immunisation Concerns…
– Children who have febrile convulsions before immunization
against diphtheria, pertussis and tetanus should be
immunized after their parents have been instructed about the
management of fever and the use of rectal diazepam or
consider acellular pertussis for future immunizations .
– Measles, mumps and rubella immunization should be given as
usual to children who have had febrile seizures, with advice
about the management of fever to the parents. Rectal
diazepam should be made available for use should a seizure
occurs.
– Febrile convulsions is not a contraindication.
– JE vaccine should be given only after fit free period of 1 year.
Unprovoked Seizures
(Afebrile Seizures)
Unprovoked Seizures
What is epilepsy?
■ The clinical diagnosis of epilepsy usually requires
– the occurrence of at least one unprovoked epileptic
seizure
– with either,
■ a second such seizure
■ or enough EEG and clinical information to convincingly
demonstrate an enduring predisposition to develop recurrences.
■ For epidemiologic and clinical purposes, epilepsy is
considered present when
– two or more unprovoked seizures
– occur in a time frame of longer than 24 hr.
Epidemiology
■ Approximately 4–10% of children experience
at least one seizure (febrile or afebrile) in the
first 16 years of life
■ The cumulative lifetime incidence of epilepsy
is 3%
■ More than half of the disorders start in
childhood
■ The ILAE Task Force on Classification has proposed a
multilevel framework for categorizing epilepsies
– Level 1: Determine if the event was an epileptic seizure
and, if so, characterize the seizure type or types based
on available clinical information as focal, generalized, or
unknown.
– Level 2: Determine the type of epilepsy the patient has
(focal, generalized, focal and generalized, or unknown).
– Level 3: Determine if the epilepsy fits into a particular
epilepsy syndrome
– Level 4: Establish a unifying diagnosis that takes into
account the epilepsy syndrome, underlying aetiologies,
■ The aetiology for the epileptic seizures should be
considered at all levels of an epilepsy diagnosis as listed
above, etiologic categories:
– Genetic
– Structural
– Metabolic
– Immune
– Infectious
– Unknown
■ Comorbidities should be considered at all levels of an
epilepsy diagnosis. These can include.
– Developmental delay
– Psychiatric symptoms
– Behavioural issues
– Academic difficulties
– Movement abnormalities, and etc.
Evaluation
■ Immediate assessment
■ History
■ Examination
■ Investigations
Evaluation (Continued…)
■ Immediate Assessment
– stabilization of the patient if the child presents during or
shortly after the seizure
– An assessment of the adequacy of
■ Airway
■ Ventilation
■ Cardiac function
– Measurement of
■ Temperature
■ Blood pressure
■ Glucose concentration
Evaluation (Continued…)
■ History
– Should search for potentially life-threatening causes of
seizures, such as,
■ Meningitis
■ Systemic sepsis
■ Unintentional or non-accidental intentional head trauma
■ Ingestion of drugs of abuse or accidental ingestion of drugs or
other toxins.
– Should aim to determine if the event was a seizure or not
– Whether the seizure has a focal onset or is generalized
Evaluation (Continued…)
■ History (Continued…)
– The duration of the seizure
– State of consciousness (retained or impaired)
– Whether an aura preceded the convulsion and
the behaviour the child was exhibiting
immediately preceding the seizure.
■ i.e. - Temporal lobe seizures may result in strange
warning feelings or aura with smell and taste
abnormalities and distortions of sound and shape.
Evaluation (Continued…)
■ History (Continued…)
– The posture of the patient
– Presence or absence and distribution of cyanosis
– Vocalizations
– Loss of sphincter control (more commonly of the
urinary bladder)
– Post-ictal state (including sleep, headache, and
hemiparesis)
 The provider taking the history should ask specifically about each
of the above symptoms as appropriate because caretakers may
not spontaneously report them.
Evaluation (Continued…)
■ In addition to clarifying the seizure semiology, a detailed
history is crucial in identifying an underlying cause for the
seizure.
– Personality changes or symptoms of increased
intracranial pressure - intracranial tumour
– Cognitive regression - Degenerative or metabolic
disease
– A history of prenatal or perinatal distress or of
developmental delay - Congenital or perinatal brain
dysfunction
– Acute to subacute personality changes, psychiatric
symptoms, and/or associated movement abnormalities -
Autoimmune aetiology
Evaluation (Continued…)
■ Examination
– A careful general and neurologic examination should be
performed.
– The examination should also be geared toward the
search for an organic cause.
– Localizing neurologic signs such as,
■ A subtle hemiparesis
■ Hyperreflexia
■ An equivocal or positive Babinski sign
might suggest a contralateral hemispheric structural
Evaluation (Continued…)
■ Examination (Continued…)
– A funduscopic exam should be performed to evaluate for
the presence of papilledema, optic neuritis, retinal
haemorrhages, etc.
– The child's head circumference, length, and weight are
plotted on a growth chart and compared with previous
measurements.
– The finding of unusual facial features or of associated
physical findings such as hepatosplenomegaly may point
to an storage disease or inborn error of metabolism
Evaluation (Continued…)
■ Examination (Continued…)
– The presence of a neurocutaneous disorder may be
indicated,
■ Vitiliginous ash leaf–type lesions - Adenoma sebaceum
■ Shagreen patches or retinal phakomas - Tuberous
sclerosis
■ Multiple café-au-lait spots - Neurofibromatosis
■ Nevus flammeus - Sturge-Weber syndrome
– Unilateral growth arrest of the thumbnail, hand, or
extremity in a child with a focal seizure disorder
suggests,
■ Arteriovenous malformation
Evaluation (Continued…)
■ Investigations
– Further laboratory testing, including
■ Serum electrolytes
■ A complete blood count
■ Urine toxicology tests
to be done considering the patient's clinical history and
examination.
– Electrocardiography (ECG) to rule out long QT or other
cardiac dysrhythmias
– A lumbar puncture is usually of limited value in the acute
workup unless the history or examination is suggestive
Evaluation (Continued…)
■ Investigations (Continued…)
– A routine EEG should be performed in all cases of a first
unprovoked non-febrile seizure to help predict the risk
of seizure recurrence.
– Emergent brain imaging with a head CT or brain MRI is
done
■ if the seizure was focal
■ if there are post-ictal focal deficits on neurologic exam
■ if the patient's status is not returning to baseline
■ in patients with trauma preceding the seizure
■ in patients with a high-risk medical history.
Evaluation (Continued…)
■ Investigations (Continued…)
– Functional imaging to detect areas of abnormal
(hypo / hyper) metabolism suggestive of seizure
foci.
– These include,
■ PET (positron emission tomography)
■ SPECT (single positron emission computed
tomography), which use isotopes and ligands,
injected and taken up by metabolically active cells.
Evaluation (Continued…)
■ Investigations (Continued…)
– Gene testing has been limited to patients,
■ Manifesting specific underlying malformational, metabolic,
or degenerative disorders
■ With severe epilepsy syndromes
■ With syndromes of Mendelian inheritance
– A full metabolic workup in,
■ Patients with drug-resistant epilepsy
■ Infants with new-onset epilepsy
■ Whom the initial testing did not reveal an underlying
aetiology
Seizure Classification (ILAE)
Epileptic Seizures
Generalized Onset Focal Onset Unknown Onset Unclassified
There is
not
enough
clinical
informati
on
Part of
one
cerebral
hemisph
ere
Synchronous
involvement
of all of
both
hemispheres
Clinical
characteristics are
unusual and a
determination of
onset cannot be
made despite an
adequate workup
Seizure Classification
(Continued…)
Seizure Classification
(Continued…)■ Focal Onset seizures
– Frontal seizures
■ Involve the motor or premotor cortex
■ May lead to clonic movements, which may travel proximally
(Jacksonian march)
■ Asymmetrical tonic seizures can be seen
■ Atonic seizures may arise from mesial frontal discharge.
– Occipital seizures
■ Cause distortion of vision
– Parietal lobe seizures
■ Cause contralateral dysaesthesias (altered sensation)
Seizure Classification
(Continued…)
■ Focal Onset seizures (Continued…)
– Temporal lobe seizures
■ The most common
■ May result in strange warning feelings or aura with smell and
taste abnormalities and distortions of sound and shape.
■ Following spread to the pre-motor cortex
– Lip-smacking
– Plucking at one’s clothing
– Walking in a non-purposeful manner (automatisms)
can be seen
■ Déjà-vu and jamais-vu are described
■ Consciousness can be impaired and the length of event is longer
than a typical absence.
Seizure Classification
(Continued…)
Seizure Classification
(Continued…)
Epilepsy Syndromes
■ There are many Epilepsy Syndromes. Few from both Generalized and
Focal epilepsy syndromes are mentioned in brief.
EEG in a typical absence seizure in childhood
absence epilepsy. There is three per second spike
and wave discharge which is bilaterally synchronous
during, and sometimes between, attacks
Epilepsy Syndromes (Continued…)
Epilepsy Syndromes (Continued…)
Epilepsy Syndromes (Continued…)
Although called benign, there may be specific learning difficulties in
some children.
Epilepsy Syndromes (Continued…)
Spike discharges from the left temporal lobe
(arrow) in a patient with complex partial seizures
caused by mesial temporal sclerosis
Left central-parietal spikes (arrow)
characteristic of benign partial epilepsy with
Centro-temporal spikes.
1-2/sec inte-rictal slow spike waves in a patient
with Lennox-Gastaut syndrome
hypsarrhythmia with irregular multifocal
high-voltage spike-and-wave activity with a
chaotic high voltage slow background
juvenile myoclonic epilepsy EEG showing 4-6/sec spike and
waves enhanced by photic stimulation
Status Epilepticus
■ Status epilepticus (SE) is a medical emergency
■ The ILAE has refined the definition of SE to reflect
the time at
– which treatment should be initiated (t1)
– which continuous seizure activity leads to long-
term sequelae (t2) depending on the type of SE.
Status Epilepticus (Continued…)
■ For generalized tonic-clonic seizures, SE is defined
as
– continuous convulsive activity
– or recurrent generalized convulsive seizure
activity without regaining of consciousness (t1 =
5 min, t2 ≥ 30 min)
■ The definition for SE consisting of focal seizures
with impaired awareness (t1 = 10 min, t2 = 30 min)
■ Absence SE (t1 = 10-15 min, t2 = unknown)
Status Epilepticus (Continued…)
Status Epilepticus (Continued…)
Status Epilepticus (Continued…)
Medications used in management of status epilepticus
Status Epilepticus (Continued…)
Medications used in management of status epilepticus
(Continued…)
Medications used in management of status epilepticus
(Continued…)
Status Epilepticus (Continued…)
Mechanisms of Seizures
1. Underlying aetiology
– Any pathology or pathologic process that can
disrupt neuronal function and connectivity and
that eventually leads to the second process -
epileptogenesis
■ i.e. - In some genetic epilepsies, a disorder in ion
channel function and/or structure is the underlying
aetiology that leads to an aberrant signal
transduction, which can cause seizures. These
mutations can involve
– Voltage-gated channels (Na+ , K+ , Ca2+ , Cl− ,
and HCN [hydrogen cyanide])
– Ligand-gated channels (nicotinic acetylcholine and
γ-aminobutyric acid A receptors [GABAA ])
2. Epileptogenesis
– The mechanism through which the brain, or part of it,
turns epileptic
– large-scale molecular cell signalling pathways are
involved
3. Epileptic state of increased excitability
– In epileptogenic neurons, a dysregulation of
glutamatergic excitation versus GABAergic inhibition
occurs, which creates a seizure focus or network
4. Seizure-related neuronal injury
– For example, many patients show acute swelling in the
hippocampus or other regions after status epilepticus
and long-term hippocampal atrophy with sclerosis on
Mechanisms of Seizures
(Continued…)
Pharmacology
Initiation of Anti-Epileptic Drugs
(AED)
■ In children, should be by a Paediatrician/ Paediatric
Neurologist.
■ Is generally not recommended after a first
unprovoked tonic-clonic seizure.
■ May be considered after a first unprovoked seizure
if,
– the individual has a neurological deficit
– a further seizure is unacceptable to the family
– brain imaging (where indicated) shows a
Choice of first AED depends on
■ The seizure type/ syndrome
■ The potential adverse effects
■ Co- morbidities
■ The availability and cost
Principles of AED Therapy
■ Should use monotherapy wherever possible
■ Unsuccessful initial therapy, try monotherapy with
another drug
■ If monotherapy in the maximum dose has failed, a
second drug should be started. The second drug
could be alternative first line.
■ If the second drug reduced the seizure frequency,
taper off the first and continue monotherapy with
the second.
■ If there is no improvement within a month, taper off
either the first or the second, depending on their
relative efficacy.
Principles of AED Therapy
(Continued…)
■ If both drugs do not work, another second line drug may
have to be introduced as monotherapy.
■ If the response is poor consider blood levels if facilities are
available.
■ Consider add on or combination therapy only when
monotherapy has failed.
■ Prior to initiation of combination therapy consider the
following.
– Is the diagnosis correct?
– Adherence to treatment
– The appropriateness of the AED for the seizure type.
– The quality of the drug.
Long term AED therapy
■ Should be planned by a specialist.
■ Involves adjustment of drug dosage according to
the weight.
■ Should include discussion with the individual
regarding possible side effects, rationale of
treatment and what should be done if a dose is
missed or during illness.
■ Should involve a simplified medication regimen with
Action of Various Antiepileptic Drugs
Choice of Drugs according to Epilepsy
type
Choice of Drugs according to Epilepsy
type
Doses of commonly used Drugs
Side effects of AED
Side effects of AED (Continued…)
Side effects of AED (Continued…)
Side effects of AED (Continued…)
Follow-up
■ For the older AEDs, before starting treatment,
baseline laboratory studies, including
– Complete blood count
– Platelets
– Liver enzymes
– Kidney function tests
– Urinalysis
are often obtained and repeated periodically.
■ Laboratory monitoring is more relevant early on,
because idiosyncratic adverse effects such as
allergic hepatitis and agranulocytosis are more
likely to occur in the first 3-6 months of therapy.
■ These laboratory studies are usually initially
checked once or twice during the 1st months, then
every 3-4 months thereafter.
Follow-up (Continued…)
Follow-up (Continued…)
■ Blood levels, if available, are indicated under the
following circumstances
– Poor response to treatment
– Poor compliance
– Toxic effects
– Management of drug interactions
Withdrawal of AED therapy should,
■ be individualized.
■ be under the guidance of the specialist.
■ be considered in those who have been seizure free
for at least two years.
■ be done slowly ( at least over 2 to 3 months)
■ take longer (up to 6 months or longer) when
withdrawing benzodiazepines and barbiturates.
■ be abandoned if seizure recurs.
■ not involve routine EEG prior to withdrawal of
treatment.
■ Algorithm for the approach to the child with a suspected
convulsive disorder
Other Treatment Options
■ Often patients who do not respond to AEDs are
candidates for steroids, IVIG, or the ketogenic diet
■ Cannabidiol (CBD) is a non-psychoactive extract of
the cannabis plant that has gained prominence as a
possible adjunct (add-on) therapy for drug-
resistant epilepsies such as Dravet and Lennox-
Gastaut syndromes
■ Precision therapy - Physiology-specific, selection of
therapy as determined by the available information
regarding the underlying pathophysiology based on
the primary specific genetic, metabolic, and/or
other cause of epilepsy in that patient.
Approach to Epilepsy Surgery
■ If a patient has failed three drugs, the chance of
achieving seizure freedom using AEDs is generally
< 10%. Therefore, proper evaluation for surgery is
necessary as soon as patients fail two or three
AEDs, usually within 2 year of the onset of epilepsy
and often sooner than 2 year.
– Focal resection
– Hemispherectomy
– multiple subpial transection
– corpus callosotomy
– nerve stimulation
Take Home Message
■ Many conditions can present like seizures – need
proper evaluation
■ There can be serious underlying issues
■ Diagnosis always by a specialist to prevent
misdiagnosis
■ Importance of Parent Education
■ Proper Treatment and follow-up
References
■ Illustrated Textbook of Paediatrics – 4th Edition
■ Nelson Textbook of Paediatrics – 21st Edition
■ Management of Seizures in Children - Sri Lankan guidelines
■ Standard Treatment Protocols - Paediatrics - 2017
Thank You
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Seizures in Childhood

  • 2. Content ■ Definitions and Terminology ■ Neonatal Seizures ■ Mimickers of Epilepsy ■ Febrile Convulsions (Provoked Seizures) ■ Unprovoked Seizures ■ Seizure Classification ■ Emergency Management– Status Epilepticus ■ Mechanisms of Seizures ■ Pharmacology and Other Treatment Options ■ Take Home Message  History  Examination  Investigations  Management  Education  Follow-up
  • 3. Terminology ■ Seizure – A transient occurrence of signs and/or symptoms resulting from abnormal excessive or synchronous neuronal activity in the brain. ■ Acute symptomatic or provoked seizures – occur secondary to an acute problem affecting brain excitability, such as an electrolyte imbalance ■ Unprovoked seizure – One that is not an acute symptomatic seizure. ■ Reflex seizures – A type of seizure precipitated by a sensory stimulus.
  • 4. Terminology (Continued…) ■ Epilepsy – A disorder of the brain characterized by an enduring predisposition to generate seizures and by the neurobiological, cognitive, psychological, and social consequences of this condition. ■ Seizure disorder – A general term that is usually used to include any one of several disorders, including epilepsy, febrile seizures, and, possibly, single seizures and symptomatic seizures secondary to metabolic, infectious, or other aetiologies (e.g., hypocalcaemia, meningitis).
  • 5. Terminology (Continued…) ■ Epileptic syndrome – A disorder that manifests as one or more specific seizure types and has a specific age of onset and a specific prognosis. ■ Epileptic encephalopathy – An epilepsy syndrome in which there is a severe EEG abnormality that is thought to result in cognitive and other impairments. ■ Epileptic disease: – A pathological condition with single specific well defined aetiology which is associated with epilepsy (e.g.
  • 6. Terminology (Continued…) ■ Benign epilepsy syndrome: – A syndrome characterized by epileptic seizures that are easily treated or require no treatment and remit without sequelae. ■ Reflex epilepsy syndrome: – A syndrome in which all epileptic seizures are precipitated by sensory stimuli ■ Focal seizures and syndromes: – Replaces the partial seizures and localization related syndromes elaborate (terms of simple partial and complex partial epileptic seizures are no longer recommended).
  • 7. Terminology (Continued…) ■ Idiopathic epilepsy syndrome: – A syndrome that is only epilepsy. No structural brain lesion or any other neurological signs. ■ Symptomatic epilepsy syndrome: – Syndrome in which seizures are due to identifiable structural lesion in brain. ■ Probably symptomatic epilepsy syndrome: – Syndromes that are believed to be symptomatic but no aetiology identified.
  • 8. What is a seizure? ■ A seizure is the manifestation of an abnormal, paroxysmal discharge of a group of cortical neurons. This discharge may produce subjective symptoms or objective signs. ■ The key features of a seizure – Paroxysmal nature of the event. – Associated abnormal movements / subtle phenomena. – Altered responsiveness or impairment of
  • 9. What is a convulsion? ■ Predominantly, an uncontrollable & involuntary contraction/relaxation or spasm of a group or groups of muscles.
  • 11. Neonatal Seizures ■ Seizures occurring in 1st month of life. ■ There are five main neonatal seizure types: – Subtle – Clonic – Tonic – Spasms – Myoclonic
  • 12. Neonatal Seizures (Continued…) ■ Seizures Versus Jitteriness – Jitteriness can be defined as ■ Rapid motor activities, such as a tremor or shake ■ That can be ended by flexion or holding the limb ■ Unlike most seizures, is usually induced by a stimulus – Seizures, ■ generally do not end with tactile or motor suppression ■ Often involve eye deviation and autonomic changes
  • 17. Mimickers of Epilepsy ■ Paroxysmal events, abnormal movements / subtle phenomena and states of altered responsiveness are common in infants and children. ■ Diagnosing epilepsy in a non epileptic is more harmful than missing the diagnosis in an epileptic. ■ The most useful diagnostic tool is an accurate history taken from an eyewitness and/or patient
  • 22. Breath-holding Attacks (Continued…) ■ Usually self limiting and no treatment is required. ■ Two types - blue and pallid. ■ Blue breath holding attacks – Provoked by upsetting an infant. – Episode starts with crying. – Followed by breath holding and apnoea. – Loss of consciousness may be associated with a few clonic jerks and bradycardia. – May occur repeatedly or sporadically. – Usually occur after 6 months of age with a peak
  • 23. Breath-holding Attacks (Continued…) ■ Pallid breath holding attacks – Provoked by upsetting an infant. – Crying prior to episode may not be apparent. – Become pale and bradycardic. – Loss of consciousness may be associated with tonic jerks. – Usually occur after 6 months of age with a peak incidence at 2 years.
  • 26. Pseudo-seizures ■ Pseudo seizure is the second most common cause of misdiagnosis. ■ Pseudo seizures could occur when there is a history of epilepsy / family history of epilepsy or even concurrent with epilepsy. ■ The difficulty arises when epilepsy coexists.
  • 28. Reflex Seizures (Stimulus- Precipitated Seizures) ■ Many patients with epilepsy can identify precipitating or provoking events that predispose them to having a seizure. ■ There is another group of patients who have seizures in response to a specifically identifiable sensory stimulus or activity and are considered to have reflex seizures. ■ Because no known reflex may be involved, more appropriate terms may be sensory-precipitated or
  • 29. Reflex Seizures (Stimulus- Precipitated Seizures) (Continued..)■ Stimuli may be – external (light, patterns, music, brushing teeth) – internal (math, reading, thinking, self-induced) ■ Reflex seizures may be – generalized – Partial – non-convulsive – Absence – myoclonic
  • 30. Reflex Seizures (Stimulus- Precipitated Seizures) (Continued..) ■ avoidance or modification of stimuli is the initial approach. ■ Such activities may include – wearing blue or polarized sunglasses – avoiding high-contrast flashing-light video games – using a TV remote control or watching TV in a well-lit room at a distance of > 8 feet – covering one eye when in a provocative
  • 31. Reflex Seizures (Stimulus- Precipitated Seizures) (Continued..)
  • 34. Provoked Seizures ■ Febrile seizures ■ Metabolic – Hypoglycaemia – Hypocalcaemia/hypomagnesaemia – Hypo/hypernatraemia ■ Head trauma ■ Meningitis/encephalitis ■ Poisons/toxins.
  • 36. Febrile Seizures ■ Febrile seizures are seizures that – occur between the ages of 6 and 60 months (peak 12-18 months) – with a temperature of 38°C (100.4°F) or higher – that are not the result of CNS infection or any metabolic imbalance – occur in the absence of a history of prior afebrile seizures.
  • 37. Febrile Seizures (Continued…) ■ An epileptic seizure occurring in childhood, – after age 1 month – associated with a febrile illness – not caused by an infection of the central nervous system (CNS) – without previous neonatal seizures or a previous unprovoked seizure – not meeting criteria for other acute symptomatic
  • 38. Febrile Seizures (Continued…) ■ Simple febrile seizure – is a primary generalized – usually tonic-clonic – attack associated with fever – lasting for a maximum of 15 min – not recurrent within a 24-hr period
  • 39. Febrile Seizures (Continued…) ■ Complex febrile seizure – is more prolonged (>15 min) – and/or is focal – and/or recurs within 24 hr ■ Febrile status epilepticus is a febrile seizure lasting longer than 30 min.
  • 40. Febrile Seizures (Continued…) ■ Most patients with simple febrile seizures have a very short post-ictal state and usually return to their baseline normal behaviour and consciousness within minutes of the seizure.
  • 41. Febrile Seizures (Continued…) ■ Febrile infection–related (or refractory ) epilepsy (FIRES) – is a very different disorder – seen predominantly in older (>5 yr) usually male children – associated with an encephalitis-like illness – but without an identifiable infectious agent ■ Children with FIRES were previously normal but subsequently develop difficult-to-treat epilepsy.
  • 42. Febrile Seizures (Continued…) ■ A few epilepsy syndromes typically start with febrile seizures ■ These are, – Generalized epilepsy with febrile seizures plus (GEFS+) ■ Autosomal dominant syndrome ■ Onset is usually in early childhood, and remission is usually in mid-childhood ■ Characterized by multiple febrile seizures and by
  • 43. Febrile Seizures (Continued…) – Severe myoclonic epilepsy of infancy (SMEI or Dravet syndrome ) ■ Most severe of the phenotypic spectrum of febrile seizure–associated epilepsies. ■ Initially characterized by febrile and afebrile unilateral clonic seizures that recur every 1 or 2 mo. ■ Seizures subsequently start to occur with lower fevers and then without fever. ■ During the second year of life, myoclonus, atypical absences, and focal seizures occur frequently and developmental delay usually follows. – Temporal lobe epilepsy secondary to mesial temporal sclerosis
  • 44. Febrile Seizures (Continued…) ■ Epidemiology – Between 2% and 5% of neurologically healthy infants and children experience at least one, usually simple, febrile seizure – Febrile seizures recur in, ■ approximately 30% of those experiencing a first episode ■ in 50% after two or more episodes ■ in 50% of infants younger than 1 year of age at febrile seizure onset – Approximately 15% of children with epilepsy have had febrile seizures
  • 45. Febrile Seizures (Continued…) ■ Risk Factors for seizure recurrence – Having no risk factors carries a recurrence risk of approximately 12%; one risk factor, 25–50%; – two risk factors, 50–59%; three or more risk factors, 73–100%.
  • 46. Febrile Seizures (Continued…) ■ Risk Factors for Occurrence of Subsequent Epilepsy After a Febrile Seizure
  • 50. Febrile Seizures (Continued…) ■ Indications for admission to hospital after a febrile seizure – First febrile seizure. – Age <18 months. – Incomplete recovery after one hour. – Any likelihood of CNS infection. – A ‘complex’ febrile seizure. – Fever has lasted more than 48 hours before onset of seizures. – Home circumstances inadequate/excessive parental anxiety/parents’ inability to cope.
  • 51. Febrile Seizures (Continued…) ■ Investigations – Blood studies (SE, Ca2+, phosphorus, Mg2+, FBC) are not routinely recommended in the workup of a child with a first simple febrile seizure. – If clinically indicated (e.g., dehydration), SE should be performed. A low sodium level is associated with a higher risk of recurrence of the febrile seizure within the following 24 hr. – CBS should be done
  • 52. Febrile Seizures (Continued…) ■ Investigations (Continued…) – Lumbar puncture should be performed ■ for all infants younger than 6 months of age ■ if the child is ill-appearing ■ at any age if there are clinical signs or symptoms of concern ■ is an option in children who have been pre-treated with antibiotics ■ is an option in a child 6-12 months of age who is deficient in Haemophilus influenzae type b and Streptococcus pneumoniae immunizations or for whom the immunization status is unknown
  • 53. Febrile Seizures (Continued…) ■ Investigations (Continued…) – EEG ■ If the child is presenting with the first simple febrile seizure and is otherwise neurologically healthy, an EEG need not be performed ■ An EEG would not predict the future recurrence of febrile seizures or epilepsy ■ EEGs performed within 2 weeks of a febrile seizure often have nonspecific slowing, usually posteriorly. Thus if an EEG is indicated, it is delayed until or repeated after more than 2 weeks have passed. ■ An EEG should generally be restricted to special cases in which epilepsy is highly suspected
  • 54. Febrile Seizures (Continued…) ■ Investigations (Continued…) – A CT or MRI is not recommended in evaluating the child after a first simple febrile seizure – The workup of children with complex febrile seizures needs to be individualized
  • 55. Febrile Seizures (Continued…) ■ Management – Fever – Acute Event (Will be discussed later) – Prophylaxis – Follow-up
  • 56. Febrile Seizures (Continued…) ■ Management of Fever – The fever should be treated to promote the child’s comfort. – An adequate fluid intake should be ensured to prevent dehydration. – Physical methods to reduce the body temperature, such as fanning, and light clothing, can be used – Paracetamol and ibuprofen (if not suspecting Dengue) are the recommended antipyretics. – Should be prescribed in correct dose
  • 57. Febrile Seizures (Continued…) ■ Management – Prophylaxis – Long-term prophylaxis ■ Phenobarbitone - frequent and substantial side effects. ■ Sodium valproate - as effective as phenobarbitone, but may produce fatal hepatic or pancreatic dysfunction in this age group. – Intermittent prophylaxis ■ Oral or rectal diazepam – As soon as the child starts fitting. – Whenever the child is febrile and before the child starts fitting. ■ Oral clobazam – Issues ■ recurrence is most likely when the fever has been present for less than one hour. ■ Child will become drowsy – will affect clinical judgment
  • 58. Febrile Seizures (Continued…) ■ Management – Evidence based Facts Management of simple febrile seizures Sri Lanka Journal of Child Health, 2017 Current Practice Management of simple febrile seizures Dr. Jithangi Wanigasinghe Consultant Paediatric Neurologist
  • 59. Febrile Seizures (Continued…) ■ Management – Follow up – No need of routine follow up generally – Specific cases should be assessed individually and followed up as necessary – If on long term prophylaxis – follow up to assess drug side effects
  • 60. Febrile Seizures (Continued…) ■ Immunisation Concerns… – Children who have febrile convulsions before immunization against diphtheria, pertussis and tetanus should be immunized after their parents have been instructed about the management of fever and the use of rectal diazepam or consider acellular pertussis for future immunizations . – Measles, mumps and rubella immunization should be given as usual to children who have had febrile seizures, with advice about the management of fever to the parents. Rectal diazepam should be made available for use should a seizure occurs. – Febrile convulsions is not a contraindication. – JE vaccine should be given only after fit free period of 1 year.
  • 62. Unprovoked Seizures What is epilepsy? ■ The clinical diagnosis of epilepsy usually requires – the occurrence of at least one unprovoked epileptic seizure – with either, ■ a second such seizure ■ or enough EEG and clinical information to convincingly demonstrate an enduring predisposition to develop recurrences. ■ For epidemiologic and clinical purposes, epilepsy is considered present when – two or more unprovoked seizures – occur in a time frame of longer than 24 hr.
  • 63. Epidemiology ■ Approximately 4–10% of children experience at least one seizure (febrile or afebrile) in the first 16 years of life ■ The cumulative lifetime incidence of epilepsy is 3% ■ More than half of the disorders start in childhood
  • 64. ■ The ILAE Task Force on Classification has proposed a multilevel framework for categorizing epilepsies – Level 1: Determine if the event was an epileptic seizure and, if so, characterize the seizure type or types based on available clinical information as focal, generalized, or unknown. – Level 2: Determine the type of epilepsy the patient has (focal, generalized, focal and generalized, or unknown). – Level 3: Determine if the epilepsy fits into a particular epilepsy syndrome – Level 4: Establish a unifying diagnosis that takes into account the epilepsy syndrome, underlying aetiologies,
  • 65. ■ The aetiology for the epileptic seizures should be considered at all levels of an epilepsy diagnosis as listed above, etiologic categories: – Genetic – Structural – Metabolic – Immune – Infectious – Unknown ■ Comorbidities should be considered at all levels of an epilepsy diagnosis. These can include. – Developmental delay – Psychiatric symptoms – Behavioural issues – Academic difficulties – Movement abnormalities, and etc.
  • 66. Evaluation ■ Immediate assessment ■ History ■ Examination ■ Investigations
  • 67. Evaluation (Continued…) ■ Immediate Assessment – stabilization of the patient if the child presents during or shortly after the seizure – An assessment of the adequacy of ■ Airway ■ Ventilation ■ Cardiac function – Measurement of ■ Temperature ■ Blood pressure ■ Glucose concentration
  • 68. Evaluation (Continued…) ■ History – Should search for potentially life-threatening causes of seizures, such as, ■ Meningitis ■ Systemic sepsis ■ Unintentional or non-accidental intentional head trauma ■ Ingestion of drugs of abuse or accidental ingestion of drugs or other toxins. – Should aim to determine if the event was a seizure or not – Whether the seizure has a focal onset or is generalized
  • 69. Evaluation (Continued…) ■ History (Continued…) – The duration of the seizure – State of consciousness (retained or impaired) – Whether an aura preceded the convulsion and the behaviour the child was exhibiting immediately preceding the seizure. ■ i.e. - Temporal lobe seizures may result in strange warning feelings or aura with smell and taste abnormalities and distortions of sound and shape.
  • 70. Evaluation (Continued…) ■ History (Continued…) – The posture of the patient – Presence or absence and distribution of cyanosis – Vocalizations – Loss of sphincter control (more commonly of the urinary bladder) – Post-ictal state (including sleep, headache, and hemiparesis)  The provider taking the history should ask specifically about each of the above symptoms as appropriate because caretakers may not spontaneously report them.
  • 71. Evaluation (Continued…) ■ In addition to clarifying the seizure semiology, a detailed history is crucial in identifying an underlying cause for the seizure. – Personality changes or symptoms of increased intracranial pressure - intracranial tumour – Cognitive regression - Degenerative or metabolic disease – A history of prenatal or perinatal distress or of developmental delay - Congenital or perinatal brain dysfunction – Acute to subacute personality changes, psychiatric symptoms, and/or associated movement abnormalities - Autoimmune aetiology
  • 72. Evaluation (Continued…) ■ Examination – A careful general and neurologic examination should be performed. – The examination should also be geared toward the search for an organic cause. – Localizing neurologic signs such as, ■ A subtle hemiparesis ■ Hyperreflexia ■ An equivocal or positive Babinski sign might suggest a contralateral hemispheric structural
  • 73. Evaluation (Continued…) ■ Examination (Continued…) – A funduscopic exam should be performed to evaluate for the presence of papilledema, optic neuritis, retinal haemorrhages, etc. – The child's head circumference, length, and weight are plotted on a growth chart and compared with previous measurements. – The finding of unusual facial features or of associated physical findings such as hepatosplenomegaly may point to an storage disease or inborn error of metabolism
  • 74. Evaluation (Continued…) ■ Examination (Continued…) – The presence of a neurocutaneous disorder may be indicated, ■ Vitiliginous ash leaf–type lesions - Adenoma sebaceum ■ Shagreen patches or retinal phakomas - Tuberous sclerosis ■ Multiple café-au-lait spots - Neurofibromatosis ■ Nevus flammeus - Sturge-Weber syndrome – Unilateral growth arrest of the thumbnail, hand, or extremity in a child with a focal seizure disorder suggests, ■ Arteriovenous malformation
  • 75. Evaluation (Continued…) ■ Investigations – Further laboratory testing, including ■ Serum electrolytes ■ A complete blood count ■ Urine toxicology tests to be done considering the patient's clinical history and examination. – Electrocardiography (ECG) to rule out long QT or other cardiac dysrhythmias – A lumbar puncture is usually of limited value in the acute workup unless the history or examination is suggestive
  • 76. Evaluation (Continued…) ■ Investigations (Continued…) – A routine EEG should be performed in all cases of a first unprovoked non-febrile seizure to help predict the risk of seizure recurrence. – Emergent brain imaging with a head CT or brain MRI is done ■ if the seizure was focal ■ if there are post-ictal focal deficits on neurologic exam ■ if the patient's status is not returning to baseline ■ in patients with trauma preceding the seizure ■ in patients with a high-risk medical history.
  • 77. Evaluation (Continued…) ■ Investigations (Continued…) – Functional imaging to detect areas of abnormal (hypo / hyper) metabolism suggestive of seizure foci. – These include, ■ PET (positron emission tomography) ■ SPECT (single positron emission computed tomography), which use isotopes and ligands, injected and taken up by metabolically active cells.
  • 78. Evaluation (Continued…) ■ Investigations (Continued…) – Gene testing has been limited to patients, ■ Manifesting specific underlying malformational, metabolic, or degenerative disorders ■ With severe epilepsy syndromes ■ With syndromes of Mendelian inheritance – A full metabolic workup in, ■ Patients with drug-resistant epilepsy ■ Infants with new-onset epilepsy ■ Whom the initial testing did not reveal an underlying aetiology
  • 79. Seizure Classification (ILAE) Epileptic Seizures Generalized Onset Focal Onset Unknown Onset Unclassified There is not enough clinical informati on Part of one cerebral hemisph ere Synchronous involvement of all of both hemispheres Clinical characteristics are unusual and a determination of onset cannot be made despite an adequate workup
  • 81. Seizure Classification (Continued…)■ Focal Onset seizures – Frontal seizures ■ Involve the motor or premotor cortex ■ May lead to clonic movements, which may travel proximally (Jacksonian march) ■ Asymmetrical tonic seizures can be seen ■ Atonic seizures may arise from mesial frontal discharge. – Occipital seizures ■ Cause distortion of vision – Parietal lobe seizures ■ Cause contralateral dysaesthesias (altered sensation)
  • 82. Seizure Classification (Continued…) ■ Focal Onset seizures (Continued…) – Temporal lobe seizures ■ The most common ■ May result in strange warning feelings or aura with smell and taste abnormalities and distortions of sound and shape. ■ Following spread to the pre-motor cortex – Lip-smacking – Plucking at one’s clothing – Walking in a non-purposeful manner (automatisms) can be seen ■ Déjà-vu and jamais-vu are described ■ Consciousness can be impaired and the length of event is longer than a typical absence.
  • 85. Epilepsy Syndromes ■ There are many Epilepsy Syndromes. Few from both Generalized and Focal epilepsy syndromes are mentioned in brief. EEG in a typical absence seizure in childhood absence epilepsy. There is three per second spike and wave discharge which is bilaterally synchronous during, and sometimes between, attacks
  • 88. Epilepsy Syndromes (Continued…) Although called benign, there may be specific learning difficulties in some children.
  • 90. Spike discharges from the left temporal lobe (arrow) in a patient with complex partial seizures caused by mesial temporal sclerosis Left central-parietal spikes (arrow) characteristic of benign partial epilepsy with Centro-temporal spikes.
  • 91. 1-2/sec inte-rictal slow spike waves in a patient with Lennox-Gastaut syndrome hypsarrhythmia with irregular multifocal high-voltage spike-and-wave activity with a chaotic high voltage slow background
  • 92. juvenile myoclonic epilepsy EEG showing 4-6/sec spike and waves enhanced by photic stimulation
  • 93. Status Epilepticus ■ Status epilepticus (SE) is a medical emergency ■ The ILAE has refined the definition of SE to reflect the time at – which treatment should be initiated (t1) – which continuous seizure activity leads to long- term sequelae (t2) depending on the type of SE.
  • 94. Status Epilepticus (Continued…) ■ For generalized tonic-clonic seizures, SE is defined as – continuous convulsive activity – or recurrent generalized convulsive seizure activity without regaining of consciousness (t1 = 5 min, t2 ≥ 30 min) ■ The definition for SE consisting of focal seizures with impaired awareness (t1 = 10 min, t2 = 30 min) ■ Absence SE (t1 = 10-15 min, t2 = unknown)
  • 97. Status Epilepticus (Continued…) Medications used in management of status epilepticus
  • 98. Status Epilepticus (Continued…) Medications used in management of status epilepticus (Continued…)
  • 99. Medications used in management of status epilepticus (Continued…) Status Epilepticus (Continued…)
  • 100. Mechanisms of Seizures 1. Underlying aetiology – Any pathology or pathologic process that can disrupt neuronal function and connectivity and that eventually leads to the second process - epileptogenesis ■ i.e. - In some genetic epilepsies, a disorder in ion channel function and/or structure is the underlying aetiology that leads to an aberrant signal transduction, which can cause seizures. These mutations can involve – Voltage-gated channels (Na+ , K+ , Ca2+ , Cl− , and HCN [hydrogen cyanide]) – Ligand-gated channels (nicotinic acetylcholine and γ-aminobutyric acid A receptors [GABAA ])
  • 101. 2. Epileptogenesis – The mechanism through which the brain, or part of it, turns epileptic – large-scale molecular cell signalling pathways are involved 3. Epileptic state of increased excitability – In epileptogenic neurons, a dysregulation of glutamatergic excitation versus GABAergic inhibition occurs, which creates a seizure focus or network 4. Seizure-related neuronal injury – For example, many patients show acute swelling in the hippocampus or other regions after status epilepticus and long-term hippocampal atrophy with sclerosis on Mechanisms of Seizures (Continued…)
  • 103. Initiation of Anti-Epileptic Drugs (AED) ■ In children, should be by a Paediatrician/ Paediatric Neurologist. ■ Is generally not recommended after a first unprovoked tonic-clonic seizure. ■ May be considered after a first unprovoked seizure if, – the individual has a neurological deficit – a further seizure is unacceptable to the family – brain imaging (where indicated) shows a
  • 104. Choice of first AED depends on ■ The seizure type/ syndrome ■ The potential adverse effects ■ Co- morbidities ■ The availability and cost
  • 105. Principles of AED Therapy ■ Should use monotherapy wherever possible ■ Unsuccessful initial therapy, try monotherapy with another drug ■ If monotherapy in the maximum dose has failed, a second drug should be started. The second drug could be alternative first line. ■ If the second drug reduced the seizure frequency, taper off the first and continue monotherapy with the second. ■ If there is no improvement within a month, taper off either the first or the second, depending on their relative efficacy.
  • 106. Principles of AED Therapy (Continued…) ■ If both drugs do not work, another second line drug may have to be introduced as monotherapy. ■ If the response is poor consider blood levels if facilities are available. ■ Consider add on or combination therapy only when monotherapy has failed. ■ Prior to initiation of combination therapy consider the following. – Is the diagnosis correct? – Adherence to treatment – The appropriateness of the AED for the seizure type. – The quality of the drug.
  • 107. Long term AED therapy ■ Should be planned by a specialist. ■ Involves adjustment of drug dosage according to the weight. ■ Should include discussion with the individual regarding possible side effects, rationale of treatment and what should be done if a dose is missed or during illness. ■ Should involve a simplified medication regimen with
  • 108. Action of Various Antiepileptic Drugs
  • 109. Choice of Drugs according to Epilepsy type
  • 110. Choice of Drugs according to Epilepsy type
  • 111. Doses of commonly used Drugs
  • 113. Side effects of AED (Continued…)
  • 114. Side effects of AED (Continued…)
  • 115. Side effects of AED (Continued…)
  • 116. Follow-up ■ For the older AEDs, before starting treatment, baseline laboratory studies, including – Complete blood count – Platelets – Liver enzymes – Kidney function tests – Urinalysis are often obtained and repeated periodically.
  • 117. ■ Laboratory monitoring is more relevant early on, because idiosyncratic adverse effects such as allergic hepatitis and agranulocytosis are more likely to occur in the first 3-6 months of therapy. ■ These laboratory studies are usually initially checked once or twice during the 1st months, then every 3-4 months thereafter. Follow-up (Continued…)
  • 118. Follow-up (Continued…) ■ Blood levels, if available, are indicated under the following circumstances – Poor response to treatment – Poor compliance – Toxic effects – Management of drug interactions
  • 119. Withdrawal of AED therapy should, ■ be individualized. ■ be under the guidance of the specialist. ■ be considered in those who have been seizure free for at least two years. ■ be done slowly ( at least over 2 to 3 months) ■ take longer (up to 6 months or longer) when withdrawing benzodiazepines and barbiturates. ■ be abandoned if seizure recurs. ■ not involve routine EEG prior to withdrawal of treatment.
  • 120. ■ Algorithm for the approach to the child with a suspected convulsive disorder
  • 121. Other Treatment Options ■ Often patients who do not respond to AEDs are candidates for steroids, IVIG, or the ketogenic diet ■ Cannabidiol (CBD) is a non-psychoactive extract of the cannabis plant that has gained prominence as a possible adjunct (add-on) therapy for drug- resistant epilepsies such as Dravet and Lennox- Gastaut syndromes ■ Precision therapy - Physiology-specific, selection of therapy as determined by the available information regarding the underlying pathophysiology based on the primary specific genetic, metabolic, and/or other cause of epilepsy in that patient.
  • 122. Approach to Epilepsy Surgery ■ If a patient has failed three drugs, the chance of achieving seizure freedom using AEDs is generally < 10%. Therefore, proper evaluation for surgery is necessary as soon as patients fail two or three AEDs, usually within 2 year of the onset of epilepsy and often sooner than 2 year. – Focal resection – Hemispherectomy – multiple subpial transection – corpus callosotomy – nerve stimulation
  • 123. Take Home Message ■ Many conditions can present like seizures – need proper evaluation ■ There can be serious underlying issues ■ Diagnosis always by a specialist to prevent misdiagnosis ■ Importance of Parent Education ■ Proper Treatment and follow-up
  • 124. References ■ Illustrated Textbook of Paediatrics – 4th Edition ■ Nelson Textbook of Paediatrics – 21st Edition ■ Management of Seizures in Children - Sri Lankan guidelines ■ Standard Treatment Protocols - Paediatrics - 2017