This document provides an overview of seizures in childhood, including definitions, epidemiology, classification, pathophysiology, evaluation, focal seizures and related epilepsy syndromes, generalized seizures and syndromes, and treatment. Key points include that focal seizures are the most common seizure type in children, various etiologies can cause seizures, and evaluation involves a detailed history, physical exam, EEG, imaging and potentially metabolic testing to identify underlying causes and guide treatment. Common benign childhood epilepsy syndromes like BECTS are also discussed.

1. Seizures in Childhood
Prepared by Dr. Amsalu( R1)

2. Contents
• Definition of Seizure and Epilepsy
• Epidemiology
• Classification of seizure
• Pathophysiology of seizures
• Evaluation Patients Presenting with Seizure
• Focal seizure and related epilepsy syndromes
• Generalized seizures and Epilepsy syndromes
• Treatment of seizures and Epilepsy

3. Definition
• Seizure
• A seizure represents the clinical expression of
abnormal, excessive, synchronous discharges of
neurons residing primarily in the cerebral cortex.
• This abnormal paroxysmal activity is intermittent and
usually self-limited, lasting seconds to a few minutes.
• When the seizure is prolonged or immediately recurrent
without a return of consciousness, this is status
epilepticus.

4. Epilepsy
• An individual is considered to have epilepsy when any
of the following exists:
• At least two unprovoked (or reflex) seizures
occurring more than 24 hours apart
• One unprovoked (or reflex) seizures and a
probability of further seizures similar to the general
recurrence risk after two unprovoked seizures (eg,
≥60 percent), occurring over the next 10 years.
• Diagnosis of an epilepsy syndrome

5. • An epileptic syndrome is a disorder that manifests as
one or more specific seizure types and has a specific age
of onset and a specific prognosis.
• An epileptic encephalopathy is an epilepsy syndrome
in which there is a severe EEG abnormality that is
thought to result in cognitive and other impairment.

6. Epidemiology
• ~ 4–10% of children experience at least one seizure
(febrile or afebrile) in the first 16 yr of life.
• The cumulative lifetime incidence of epilepsy is 3%,
• The annual prevalence is 0.5–1.0 %
• In most studies, incidence rates are slightly higher in
males than in females
• The incidence is higher in lower socioeconomic groups
• Focal (partial) seizures are the most common seizure
type in all age groups .

7. SEIZURE TYPES
Focal-Onset Seizures
• Motor Onset
Tonic
Clonic
Atonic
Myoclonic
Hyperkinetic
Epileptic spasms
Automatisms
• Non–Motor Onset
Behavior arrest
Sensory
Cognitive
Emotional
Autonomic
Awareness Descriptor
Aware
Impaired awareness
Generalization Descriptor
Focal to bilateral tonic-clonic
(previously called secondary
generalized seizure )

8. • Motor
Tonic-clonic
Tonic
Clonic
Atonic
Myoclonic
Myoclonic-atonic
Myoclonic-tonic-clonic
Epileptic spasms
• Non–Motor (Absence)
Typical
Atypical
Myoclonic
Eyelid myoclonia
Generalized-Onset Seizures

9. • Unknown-Onset Seizures
Motor
Tonic-clonic
Epileptic spasms
Non–Motor
Behavior arrest
• Unclassified Seizures
9

10. Diagnostic and Classification Scheme of
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
etiologies, and associated comorbidities.

11. • The etiology 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, behavioral issues, academic difficulties,
movement abnormalities, and many others.

12. Pathophysiology
 The causes of epilepsy are most often multifactorial, and
it is useful to consider three general factors:
1) The susceptibility of individual brains to generate
seizures in response to epileptogenic perturbations .
-Virtually all antiepileptic drugs work by raising the
threshold.
2) The specific epileptogenic abnormality, which could
be an acquired lesion of the brain or a genetic
disturbance.
-Specific epileptogenic disturbances may require
specific treatment that can eliminate seizures.
3) Precipitating events that cause seizures to occur at a
given point in time 12

13. • A seizure is the clinical manifestation of a hyperexcitable
neuronal network, in which the electrical balance
underlying normal neuronal activity is pathologically
altered—excitation predominates over inhibition .
• Seizure discharge transmission ultimately depends on
excitatory glutamatergic synapses.
• Seizures may arise from areas of neuronal death, and
these regions of the brain may promote development of
hyperexcitable synapses that can cause seizures.
• Inhibitory neurons are selectively damaged and
remaining principal excitatory neurons become
hyperexcitable.
• Aberrant excitatory circuits are formed as part of
reorganization after injury.
13

14. Cellular Mechanisms of Seizure Generation
• Excitation (too much)
• Ionic-inward Na+, Ca++ currents
• Neurotransmitter: glutamate, aspartate
• Inhibition (too little)
• Ionic-inward CI-, outward K+ currents
• Neurotransmitter: GABA
14

15. Evaluation of the first Seizure
• The initial evaluation of an infant or a child during or
shortly after a suspected seizure should include an
assessment of the adequacy of the airway, ventilation,
and cardiac function, as well as measurement of
temperature, RBS, Serum Electrolytes
• For acute evaluation of the first seizure, the physician
should search for potentially life-threatening causes
of seizures, such as meningitis, systemic sepsis , head
trauma, and ingestion of drugs of abuse or accidental
ingestion of drugs or other toxins.
15

16. • History
• Normal neurologic examination and
neuroimaging studies in majority
• A careful history is the cornerstones of an
accurate diagnosis.
• A detailed account of the child's behavior
preceding, during, and following a "spell" is
critical
16

17. Setting in which episodes occur
• Most seizures occur at random and without warning.
• In contrast, many nonepileptic spells have
characteristic precipitating circumstances or occur in
specific locations.
• Important questions to consider include:
• Were the seizures primarily nocturnal?
• Was the child taking medication?
• Did the seizures occur only with illness and fever?
• Did the seizures occur only when the child was relaxed
and never occur when actively involved in some type of
activity? (More likely nonseizure events).
17

18. Behavior immediately prior to the event
• On rare occasions, seizures may be precipitated by
environmental stimuli such as sound or an
unexpected touch (reflex epilepsy).
• More commonly, no obvious precipitating
circumstances are present.
18

19. Behavior during the event
• A nonepileptic seizure should be suspected if the
patient has generalized motor activity with normal
responsiveness, particularly if it lasts longer than 5
minutes.
• Repeatedly and consistently stereotyped behaviors
suggest seizures as compared to nonepileptic events.
• A nonepileptic seizure should be considered if the
patient keeps the eyes tightly closed during the
seizure
• Generalized motor seizures cannot be interrupted
by vocal or tactile/painful stimulation
19

20. Behavior after the event
• What was the patient's behavior after the event
(postictal state)?
• Did he or she recover immediately, or was there
confusion or somnolence?
• Was the child able to communicate verbally
immediately after the event (eg, could the patient form
appropriate and full sentences; was the child oriented;
could the child follow complex or simple verbal
commands)?
20

21. • Children with epilepsy are also more likely to have
psychiatric disorders such as depression, anxiety,
and attention deficit hyperactivity disorder.
• Specific assessment and management of these
conditions is likely to be beneficial in the child’s
overall prognosis.
• A developmental history should be obtained, with
particular attention given to any plateau or loss of
developmental milestones
• The examiner should search for a history of
previous illnesses that are associated with seizures
(eg, meningitis, hypoxic-ischemic encephalopathy,
head trauma).
• A detailed family history is mandatory
21

22. PHYSICAL EXAMINATION
• In addition to searching for medical causes of the
patient's seizures, close attention should be paid to
the eye examination
• The abdominal examination may reveal
hepatosplenomegaly, suggesting a storage disease.
• A cardiac examination, including an ECG, is
necessary if concern exists about a cardiogenic
cause for the patient's episodes.
• The skin examination is of particular importance in
the evaluation of children with seizures as many
neurocutaneous disorders are associated with
epilepsy
22

23. Nervous System Examination
• Localizing neurologic signs, such as a subtle
hemiparesis with hyperreflexia , an equivocal or
positive Babinski sign, and pronator drifting of an
extended arm with eyes closed, might suggest a
contralateral hemispheric structural lesion,
such as a slow-growing glioma, as the cause of the
seizure disorder.
• Unilateral growth arrest of the thumbnail, hand, or
extremity in a child with a focal seizure
disorder suggests a chronic condition, such as a
porencephalic cyst
23

24. Investigations
• EEG
• a valuable adjunct to the assessment of children
with suspected seizures.
• Virtually every child with recurrent seizures
should have an EEG awake and while sleeping.
• Each EEG recording should be performed with
specific questions in mind, an understanding and
anticipation of the possible results, and a planned
response to these results.
24

25. NEUROIMAGING
• The initial investigation should be directed toward
finding a structural abnormality as the basis of the
seizures, thereby avoiding expensive laboratory
tests for the less common inherited neurometabolic,
degenerative, or developmental disorders
• MRI is the preferred neuroimaging study for the
evaluation of a child with seizures.
• A CT scan is most often used for emergency
department assessment.
25

26. LABORATORY TESTING
• CBC and platelet count,
• Liver and renal function tests,
• Glucose,
• Electrolytes,
• Total protein,
• Albumin, and globulin.
26

27. In patients with drug-resistant epilepsy, or in infants
with new-onset epilepsy in whom the initial testing
did not reveal an underlying etiology, a full metabolic
workup, including amino acids, organic acids,
biotinidase , and CSF studies, is needed
• Serum (and CSF) amino acid analysis
• Urine for quantitative organic acids
• Serum calcium, glucose, liver function tests
• Serum acylcarnitine profile, ammonia, lactate and
pyruvate
• Arterial blood gas and pH
• CSF lactate and glucose (paired with blood glucose)
• Chromosomal karyotype
• Serum and CSF autoantibodies (eg, anti-N-methyl-
D-aspartate receptor [NMDAR] antibodies)
27

28. Focal Seizures and Related Epilepsy
Syndromes
• Focal seizures with preserved or impaired
awareness can each occur in isolation, one can
temporally lead to the other (usually from
preserved to impaired awareness),
• and/or each can progress into secondary
generalized seizures, called focal to bilateral
tonic-clonic seizures, although less commonly
the secondary generalized seizure may be tonic,
clonic, or atonic.

29. Focal Seizures With Preserved
Awareness
• These can take the form of sensory seizures (auras,
called focal aware seizures) or brief motor seizures,
the specific nature of which gives clues as to the
location of the seizure focus.
• Brief motor seizures are the most common and
include focal tonic, clonic, or atonic seizures.
• Often there is a motor (Jacksonian) march from
face to arm to leg,adversive head and eye movements
to the contra lateral side, or postictal (Todd) paralysis
that can last minutes or hours, and sometimes longer

30. Focal Seizures With Impaired Awareness
• These seizures usually last 1-2 min and are often
preceded by an aura, such as a rising abdominal
feeling, déjà vu or déjà vécu, a sense of fear, complex
visual hallucinations, micropsia or macropsia
(temporal lobe), generalized difficult-to characterize
sensations (frontal lobe), focal sensations (parietal
lobe), or simple visual experiences (occipital lobe).

31. • Children younger than 7 yr old are less likely than
older children to report auras, but parents might
observe unusual preictal behaviors that suggest the
experiencing of auras.
• Subsequent manifestations consist of decreased
responsiveness, staring, looking around seemingly
purposelessly, and automatisms.

32. Cont…
• The patient might appear to react to some of the
stimulation around him or her but does not later
recall the epileptic event.
• At times, walking and/or marked limb flailing and
agitation occur, particularly in patients with frontal
lobe seizures.
• Frontal lobe seizures often occur at night and can
be very numerous and brief, but other complex
partial seizures from other areas in the brain can
also occur at night.

33. Cont…
• There is often contra lateral dystonic posturing of
the arm and, in some cases, unilateral or bilateral
tonic arm stiffening.
• Some seizures have these manifestations with
minimal or no automatisms.
• Others consist of altered consciousness with contra
lateral motor, usually clonic, manifestations.
• After the seizure, the patient can have postictal
automatisms, sleepiness, and/or other transient focal
deficits such as weakness (Todd paralysis) or
aphasia.

34. Focal to Bilateral Tonic- Clonic
Seizures
 These can either start with generalized clinical
phenomena (from rapid spread of the discharge from the
initial focus) or as focal seizures with subsequent
clinical generalization.
 There is often adversive eye and head deviation to the
side contra lateral to the side of the seizure focus,
followed by generalized tonic,clonic, or tonic- clonic
activity.

35. • Tongue biting, urinary and stool incontinence, vomiting with
risk of aspiration, and cyanosis are common.
• Fractures of the vertebrae or humerus are rare complications.
• Most such seizures last 1-2 min.
• Focal tonic or focal to bilateral tonic-clonic seizures often
manifest as adversive head deviation to the contra lateral side,
fencing, hemi- or full figure-of-four arm, and/or Statue of
Liberty postures.
• These postures usually suggest a frontal origin and, when
awareness is preserved during them, favor that the seizure
originated from the medial frontal supplementary motor area.

36. Cont…
• EEG in patients with focal/partial seizures usually
shows focal spikes or sharp waves in the lobe where
the seizure originates.
• A sleep-deprived EEG with recording during sleep
increases the diagnostic yield and is advisable in all
patients whenever possible.
• Despite that, approximately 15% of children with
epilepsy initially have normal EEGs because the
discharges are relatively infrequent or the focus is
deep.

37. Cont…
• If repeating the test does not detect paroxysmal
findings, longer recordings in the laboratory or
using ambulatory EEG or even inpatient 24-hr video
EEG monitoring may be helpful.
• The latter is particularly helpful if the seizures are
frequent enough, because it then can allow
visualization of the clinical events and the
corresponding EEG tracing .

38. Cont…
• Brain imaging is critical in patients with focal
seizures.
• In general, MRI is preferable to CT, which misses
subtle but, occasionally, potentially clinically
significant lesions.
• MRI can show pathologies such as changes as a result
of previous strokes or hypoxic injury, malformations,
medial temporal sclerosis, arteriovenous
malformations, inflammatory pathologies, or tumors .

39. Cont…

40. Benign Epilepsy Syndromes With Focal
Seizures
• The most common such syndrome is benign
childhood epilepsy with centrotemporal spikes
(BECTS), which typically starts during childhood
(ages,3-10 yr) and is outgrown by adolescence.
• The child typically wakes up at night due to a focal
seizure with preserved awareness causing buccal and
throat tingling and tonic or clonic contractions of one
side of the face, with drooling and inability to speak
but with preserved consciousness and comprehension.

41. • Focal seizures with impaired awareness and secondary
generalized seizures can also occur.
• EEG shows typical wide-based Centro temporal spikes
that are markedly increased in frequency during
drowsiness and sleep.
• MRI is normal. Patients respond very well to
antiepileptic drugs (AEDs) such as oxcarbazepine
and carbamazepine.
• In some patients who only have rare and mild
seizures, treatment might not be needed.

42. Cont…
• Atypical BECTS is a less common variant of the
disorder characterized by often a younger age of
onset, multiple seizure types including drop attacks,
atypical EEG patterns including secondary bilateral
synchrony, and/or other co morbidities such as
developmental delay.

43. • Benign epilepsy with occipital spikes can occur in early
childhood (Panayiotopoulos type ) and manifests with focal
seizures with impaired awareness and with ictal vomiting, or
they appear in later childhood (Gastaut type ) as focal
seizures with impaired awareness, visual auras, and migraine
headaches that occur in dependently or postictally (epilepsy–
migraine sequence).
• Both are typically outgrown in a few years. In infants, several
less common benign infantile familial convulsion syndromes
have been reported.
• For some of these, the corresponding gene mutation and its
function are known

44. • A number of benign infantile non familial
syndromes have been reported, including focal
seizures with impaired awareness with temporal foci,
focal to bilateral tonic clonic seizures with variable
foci, tonic seizures with midline foci, and focal
seizures in association with mild gastroenteritis.
• All of these have a good prognosis and respond to
treatment promptly; often, only short-term therapy.
(e.g., 6 mo), if any therapy, is needed.

45. • Nocturnal autosomal dominant frontal
lobe epilepsy has been linked to acetylcholine-
receptor and to KCNT1 gene mutations.
• It manifests with nocturnal seizures with dystonic
posturing, agitation, screaming, and kicking that
respond promptly to carbamazepine.
• Several other less frequent familial benign epilepsy
syndromes with different localizations have also
been described, some of which occur exclusively or
predominantly in adults.

46. Severe Epilepsy Syndromes With Focal
Seizures
• Symptomatic structural/metabolic epilepsy
secondary to focal brain lesions has a higher
chance of being severe and refractory to therapy
than genetic (idiopathic)epilepsy.
• It is important to note that many patients with focal
lesions, for example, old strokes or brain tumors,
either never have seizures or have well controlled
epilepsy.
• In infants, drug-resistant epilepsy with focal
seizures is often caused by severe metabolic
problems, hypoxic-ischemic injury, or congenital
malformations.

47. • In addition, in this age-group, a syndrome of
multifocal severe partial seizures with progressive
mental regression and cerebral atrophy called
epilepsy of infancy with migrating focal seizures
(EIMFS)has been described.
• Some cases of EIMFS are secondary to mutations in
the calcium-sensitive potassium channel KCNT1.
• Brain malformations causing focal epilepsy include
focal cortical dysplasia, hemimegalencephaly,
Sturge-Weber cutaneous lesion, tuberous sclerosis,
and congenital tumors such as ganglioglioma and
dysembryoplastic neuroepithelial tumors, as well as
others.

48. • The intractable seizures can be focal seizures with or
without impaired awareness, focal to bilateral tonic-
clonic seizures, or combinations them.
• If secondary generalized seizures predominate and
take the form of absence-like seizures and drop
attacks, the clinical picture can mimic the generalized
epilepsy syndrome of Lennox- Gastaut syndrome and
has been termed by some pseudo–Lennox- Gastaut
syndrome.

49. • Temporal lobe epilepsy can be caused by any
temporal lobe lesion.
• A common cause is mesial (also termed medial )
temporal sclerosis, a condition often preceded by
febrile seizures and, rarely, genetic in origin.
• Pathologically, these patients have atrophy, gliosis or
cortical dysplasia of the hippocampus, and, in
some, these conditions of the amygdala. Some
patients have mutations on the SUCO gene.
• Medial temporal lobe epilepsy is the most common
cause of surgically remediable partial epilepsy in
adolescents and adults.

50. • Occasionally, in patients with other structural or
genetic focal or generalized epilepsies, the focal
discharges are so continuous that they cause an
epileptic encephalopathy.
• Activation of temporal discharges in sleep can lead
to loss of speech and verbal auditory agnosia
(Landau- Kleffner epileptic aphasia syndrome).

51. Cont…
• Activation of secondary generalized and at times focal
discharges in sleep leads to more global delay secondary
to the syndrome of continuous spike waves in slow-
wave sleep (>85% of the slow-wave sleep recording is
dominated by discharges).
• The syndrome of Rasmussen encephalitis is a form of
chronic encephalitis that manifests with unilateral
intractable partial seizures, epilepsia partialis continua,
and progressive hemiparesis of the affected side, with
progressive atrophy of the contralateral hemisphere.
• The etiology is usually unknown, although autoimmune
etiologies have been hypothesized.

52. Generalized Seizures and Related
Epilepsy Syndromes
Absence Seizures
• Typical absence seizures usually start at 5-8 yr of age and are
often, due to their brevity, overlooked by parents for many
months even though they can occur up to hundreds of times per
day.
• Unlike focal seizures with impaired awareness they
do not have an aura, usually last for only a few seconds, and are
accompanied by eyelid flutter or upward rolling of the eyes but
typically not by the usually more florid automatisms seen in
focal seizures with impaired awareness (absence seizures can
have simple automatisms such as lip smacking or picking at
clothing, and the head can very minimally fall forward).
•
).

53. Cont…..
• Absence seizures do not have a postictal period and
are characterized by immediate resumption of what
the patient was doing before the seizure.
• Hyperventilation for 3-5 min can precipitate the
seizures and the accompanying 3-Hz spike-and–
slow-wave discharges.

54. Cont…
• The presence of eye closure eyelid myoclonia
(Jeavons syndrome) and periorbital, perioral, or
limb myoclonic jerks (the latter called myoclonic
absences ) with the typical absence seizures usually
predicts difficulty in controlling the seizures with
medications.

55. Cont…
• Early-onset absence seizures (<4 yr of age) or drug
resistance should trigger evaluation for a glucose
transporter defect, which is often associated with
low CSF glucose levels and an abnormal
sequencing test of the transporter gene.

56. Cont…
• Atypical absence seizures have associated
myoclonic components and tone changes of the
head (head drop) and body and are also usually
more difficult to treat.
• They are precipitated by drowsiness and are usually
accompanied by 1- to 2-Hz spike-and–slow-wave
discharges.

57. Cont..
• Juvenile absence seizures are similar to typical
absences but occur at a later age and are
accompanied by 4- to 6-Hz spike-and–slow-wave
and polyspikeand–slow-wave discharges.
• These are usually associated with juvenile
myoclonic epilepsy

58. Generalized Motor Seizures
• The most common generalized motor seizures are
generalized tonic-clonic seizures that can be either
primarily generalized (bilateral) or focal to bilateral
tonic-clonic from a unilateral focus.
• If there is no partial component, the seizure usually
starts with loss of consciousness and ,at times, with
a sudden cry, upward rolling of the eyes, and a
generalized tonic contraction with falling, apnea,
and cyanosis.
• In some, a clonic or myoclonic component
precedes the tonic stiffening.

59. Cont…
• The tonic phase is followed by a clonic phase that,
as the seizure progresses, shows slowing of the
rhythmic contractions until the seizure stops,
usually 1-2 min later.
• Incontinence and a postictal period often follow.
The latter usually lasts for a few minutes up to
several hours with semicoma or obtundation and
postictal sleepiness, weakness, ataxia, hyper- or
hyporeflexia, and headaches

60. Cont…
There is a risk of aspiration and injury. First aid
measures include positioning the patient on his or
her side, clearing the mouth if it is open, loosening
tight clothes or jewelry, and gently extending the
head and, if possible, insertion of an airway by a
trained professional.
• The mouth should not be forced open with a foreign
object (this could dislodge teeth, causing aspiration)
or with a finger in the mouth (this could result in
serious injury to the examiner's finger).

61. Cont..
• Many patients have single genetic generalized
tonic-clonic seizures that may be associated with
intercurrent illness or with a cause that cannot be
ascertained Generalized tonic, atonic, and a static
seizures often occur in severe generalized pediatric
epilepsies.
• Generalized myoclonic seizures can occur in either
benign or difficult-to-control generalized epilepsies.

62. Benign Generalized Epilepsies
• Childhood absence epilepsy typically starts in
mid-childhood, and most patients outgrow it before
adulthood.
• Approximately 25% of patients also
develop generalized tonic-clonic seizures, half
before and half after the onset of absences.
• Benign myoclonic epilepsy of infancy consists of
the onset of myoclonic and other seizures during the
first year of life, with generalized 3-Hz spike-and–
slow-wave discharges.
• Often, it is initially difficult to distinguish this type
from more severe syndromes, but follow-up
clarifies the diagnosis.

63. • Juvenile myoclonic epilepsy (Janz syndrome) is the
most common generalized epilepsy in young adults,
accounting for 5% of all epilepsies. It has been linked
to mutations in many genes, including CACNB4;
CLNC2; EJM2, 3, 4, 5, 6, 7, 9; GABRA1; GABRD; and
Myoclonin1/EFHC1
• Typically, it starts in early adolescence with one or
more of the following manifestations: myoclonic
jerks in the morning, often causing the patient to drop
things; generalized tonic-clonic or clonic-tonic-clonic
seizures upon awakening; and juvenile absences.
• Sleep deprivation, alcohol (in older patients), and
photic stimulation, or, rarely, certain cognitive
activities can act as precipitants

64. Cont….
• The EEG usually shows generalized 4- to 5-Hz
polyspike-and–slow-wave discharges.
• There are other forms of generalized epilepsies such as
photo paroxysmal epilepsy, in which generalized tonic-
clonic, absence, or myoclonic generalizedseizures are
precipitated by photic stimuli such as strobe lights,
flipping through TV channels, and viewing video games.
Other forms of reflex (i.e., stimulus provoked ) epilepsy
can occur;
• associated seizures are usually generalized, although
some may be focal

65. Severe Generalized Epilepsies
• Severe generalized epilepsies are associated with
intractable seizures and developmental delay.
• Early myoclonic infantile encephalopathy starts
during the first 2 mo of life with severe myoclonic
seizures and a burst suppression pattern on EEG.
• It is usually caused by inborn errors of metabolism
such as non ketotic hyperglycinemia.

66. Cont…..
• Early infantile epileptic encephalopathy
(Ohtahara syndrome) has a similar age of onset
and EEG but manifests as tonic seizures and is
usually caused by brain malformations or syntaxin-
binding protein 1 mutations.

67. Cont…
• The term early infantile epileptic encephalopathy
(EIEE) has also been applied, mostly by genetics
experts, to the increasing number of other genetic
epileptic encephalopathies and developmental
epileptic encephalopathies that are associated with an
increasing number of specific genes with pathogenic
mutations these may or may not manifest as
Ohtahara syndrome, but all share the characteristic of
early-onset epileptic encephalopathy.

68. Cont…
• Severe myoclonic epilepsy of infancy (Dravet
syndrome) starts as focal febrile status epilepticus
or focal febrile seizures and later manifests as
myoclonic and other seizure types.

69. Cont….
• Severe generalized epilepsies are associated with
intractable seizures and developmental delay.
• Early myoclonic infantile encephalopathy starts
during the first 2 mo of life with severe myoclonic
seizures and a burst suppression pattern on EEG.
• It is usually caused by inborn errors of metabolism
such as non ketotic hyperglycinemia.

70. Cont…
• West syndrome starts between the ages of 2 and 12
mo and consists of a triad of infantile epileptic
spasms that usually occur in clusters (particularly in
drowsiness or upon arousal), developmental
regression, and a typical EEG picture called
hypsarrhythmia .
• Hypsarrhythmia is a high voltage, slow, chaotic
background with multifocal spikes. Patients with
cryptogenic (sometimes called idiopathic, now
referred to as unknown etiology).

71. Cont…
• West syndrome have normal development before
onset, whereas patients with symptomatic West
syndrome have preceding developmental delay
owing to perinatal encephalopathies, malformations,
underlying metabolic disorders, or other etiologies.

72. Cont…
• In males, West syndrome can also be caused by
ARX gene mutations (often associated with
ambiguous genitalia and cortical migration
abnormalities).
• West syndrome, especially in cases of unknown
etiology (cryptogenic cases, i.e., cases that are not
symptomatic of a metabolic or structural brain
disorder), is a medical emergency because a delay
in diagnosis of 3 wk or longer can affect the long-
term prognosis.

73. Lennox-Gastaut syndrome
• Typically starts between the ages of 2 and 10 yr
• Consists of a triad of developmental delay, multiple
seizure types that as a rule include atypical
absences, and myoclonic, astatic, and tonic seizures,
as well as specific EEG abnormalities.
• The tonic seizures occur either in wakefulness
(causing falls and injuries) or also, typically, in
sleep.
• The third component is the EEG findings : 1- to 2-
Hz spike and slow waves, polyspike bursts in sleep,
and a slow background in wakefulness.
• Patients commonly have tonic, myoclonic, atonic,
and other seizure types causing falls and are
difficult to control.

74. Cont…
• Most are left with long-term cognitive impairment
and intractable seizures despite multiple therapies.
• Some, but not all, patients start with Ohtahara
syndrome, develop West syndrome, and then
progress to Lennox-Gastaut syndrome.

75. • Myoclonic astatic epilepsy ( Doose syndrome) is a
syndrome similar to, but milder than, Lennox-
Gastaut syndrome that usually does not have tonic
seizures or polyspike bursts in sleep.
• The prognosis is more favorable than that for
Lennox- Gastaut syndrome

76. • Landau- Kleffner syndrome is a rare condition of
presumed autoimmune but sometimes also of genetic
(GRIN2A mutations) etiology.
• It is characterized by loss of language skills and by
verbal auditory agnosia in a previously normal child.
• At least 70% have associated clinical seizures, but some
do not.
• The seizures when they occur are of several types,
including focal with preserved awareness, focal to
bilateral tonic-clonic, atypical absence, focal with
impaired awareness, and occasionally myoclonic
seizures.
• High-amplitude spike-and wave discharges predominate
and tend to be bitemporal. In the later evolutionary stages
of the condition, the EEG findings may be normal.

77. Cont…
• The spike discharges are always more apparent
during non–rapid eye movement sleep; thus, a child
in whom Landau- Kleffner syndrome is suspected
should have an EEG during sleep.
• CT and MRI studies typically yield normal results.
In the related but clinically distinct epilepsy
syndrome with continuous spike waves in slow
wave sleep (CSWS) , the discharges occur in >
85% of the slow-wave sleep, a finding termed
electrical status epilepticus in sleep (ESES).

78. Cont…
• ESES can also occur in Landau- Kleffner syndrome,
but in CSWS the discharges are usually frontal or
generalized and the delays usually global.
• The approach to and therapy for the two syndromes
are similar.

79. Cont…
• Valproic acid is often the anticonvulsant that is used
first to treat the clinical seizures and may help the
aphasia. Some children respond to clobazam, to the
combination of valproic acid and clobazam, or to
levetiracetam.
• For therapy of the aphasia, nocturnal diazepam (0.2-0.5
mg/kg orally at bedtime for several months) is often
used as first- or second-line therapy, as are oral steroids.
Oral prednisone is started at 2 mg/kg/day for 1-2 mo,
then weaned over a period of 1-3 mo.

80. • Alternatively, monthly infusions of high-dose
intravenous methylprednisolone have been used
instead of oral steroids.
• Long-term therapy is often needed irrespective of
which drug(s) elicit a patient response.
• If the seizures and aphasia persist after diazepam
and steroid trials, then a course of intravenous
immunoglobulins should be considered because
many patients can respond to that.
• It is imperative to initiate speech therapy and
maintain it for several years, because improvement
in language function occurs over a prolonged
period.

81. • Developmental delay, epilepsy, and neonatal
diabetes is caused by activating mutations in the
adenosine triphosphate–sensitive potassium
channels.
• Sulfonylurea drugs that block the potassium channel
treat the neonatal diabetes and probably also
favorably affect the central nervous system (CNS)
symptoms and affect seizures.

82. Treatment of specific epilepsies
• After a first seizure, if the risk of recurrence is low,
as when the patient has a normal neuro
developmental status, EEG, and MRI (risk ~ 20%),
treatment is usually not started.
• If the patient has an abnormal EEG, MRI,
development status, and/or neurologic exam and/or
has a positive family history of epilepsy, the risk is
higher, and often treatment is started .

83. • Treatment with antiseizure drugs is not indicated for
the prevention of the development of epilepsy.
• Treatment with antiseizure drugs may be considered
when the benefits of reducing the risk of a second
seizure are greater than the risks of pharmacologic
and psychosocial side effects.
83

84. Cont…
• An important part of the management of a patient
with epilepsy is educating the family and the child
about the disease, its management, and the
limitations it might impose and how to deal with
them.
• It is important to establish a successful therapeutic
alliance .

85. Selection of an antiseizure drug
• Single-drug therapy is the goal of epilepsy treatment.
• Monotherapy is associated with better compliance,
fewer adverse effects, less potential for teratogenicity,
and lower cost than is polytherapy.
• Drug interactions are avoided and pharmacokinetics
are simplified.
• The optimal choice of antiseizure drug depends on
the type of seizure and the epilepsy syndrome.
85

86. • Most children with epilepsy achieve reasonably good
seizure control with antiseizure drug monotherapy or
polytherapy, but some are refractory despite numerous
medications.
• Medical treatment failure is often apparent early in the
course of treatment.
• In these cases, referral to a comprehensive epilepsy
center is appropriate to explore additional therapeutic
options, including epilepsy surgery, vagus nerve
stimulation, and the ketogenic diet.
86

87. • Withdrawal of antiseizure drug therapy should be
considered in most children after two years without
seizures, regardless of the etiology of the seizures.
• The likelihood of recurrence after a two-year period
without seizures is approximately 30 to 40 percent.
• Antiseizure drugs should be tapered rather than
halted abruptly.
87

88. Choice of Drug According to Seizure Type
and Epilepsy Syndrome
• West syndrome is best treated with hormonal therapy in
the form of either ACTH injections or, possibly, oral
steroids
• Dravet syndrome is usually treated with benzodiazepines
such as clobazamand with valproate. The ketogenic diet
can also be useful in patients with this syndrome,
including cases with refractory status.
• Absence seizures are most often initially treated with
ethosuximide, which is as effective as, but less toxic than,
valproate; both are more effective than lamotrigine (which
has fewer side effects than valproate).

89. • Benign myoclonic epilepsies are often best treated with
valproate,particularly when patients have associated
generalized tonic-clonic and absence seizures.
Zonisamide, clonazepam, lamotrigine, and topiramate
are alternatives.
• Severe myoclonic epilepsies are treated with
medications effective for Lennox-Gastaut syndrome,
such as topiramate, clobazam, valproate, and
zonisamide. Levetiracetam may also have efficacy in
myoclonic epilepsies.
• Focal and focal to bilateral tonic-clonic seizures can
be treated with oxcarbazepine, levetiracetam,
carbamazepine, phenobarbital, topiramate,
lacosamide, zonisamide, valproic acid, lamotrigine,
clobazam, perampanel, or clonazepam .
• Oxcarbazepine and levetiracetam are often being
used first.

90. • In some cases, particularly for generalized epilepsy
syndromes, seizures may be aggravated by the
administration of a narrow-spectrum antiseizure
drug, when a broad-spectrum antiseizure drug is
more appropriate.
• As examples, carbamazepine and phenytoin have
been reported to worsen absence and myoclonic
seizures in individuals with idiopathic generalized
epilepsy
90

91. 91

92. 92

93. Referances
• Up-to-date
• Nelson 21st Edition
93