Approach to Seizure and Epilepsy in Children

1. Seizure in Children

2. Seizure –
•Transient occurrence of signs and/or symptoms
from abnormal excessive neuronal activity in
brain.
Types –
•based on mode of onset:
focal,
generalized,
unknown onset.

3. •Focal(partial)seizures - initial activation of neurons
limited to part of one cerebral
hemisphere.
•Focal aware seizure (Simple partial seizure)-
No alteration in
consciousness.
•Focal seizures with impaired awareness

4. •Generalized seizures –
Involvement of both
hemispheres.
•Seizure of unknown onset-
not enough clinical
information to

5. Epilepsy
A predisposition to generate seizures and its
neurobiologic, cognitive, psychological, and
social
consequences.
•Clinical Diagnosis:–
At least one unprovoked seizure
with
either a second such seizure or
enough EEG and clinical

6. •For epidemiologic/clinical purposes –
Epilepsy is considered present when two or more
unprovoked
seizures occur in a time frame of longer than 24 hr.
•Approximately 4–10% of children experience at least one
seizure (febrile or afebrile) in the first 16 yr of life.
•Cumulative lifetime incidence of epilepsy is 3%, and more
than
half of the disorders start in childhood.

7. Seizure disorder
A general term used to include Epilepsy,
Febrile
seizures, Single seizures and Symptomatic
seizures secondary to metabolic, infectious,
or
other etiologies (Hypocalcemia, Meningitis).

8. 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 result in
cognitive and other impairments.

9. Evaluation of the First Seizure
•Assessment of:
Adequacy of Airway,
Ventilation,
Cardiac function,
Measurement of temperature,
Blood Pressure,
Glucose,
Electrolytes.

10. •Search for potentially life-threatening
cause :
Meningitis,
Sepsis,
Head Trauma,
Drugs Abuse
Accidental ingestion of drugs/ toxins.

11. •Determine whether onset was focal or
generalized.
•Focal seizures:
-In adolescence: a localized lesion,
-In childhood: secondary to a lesion or result of
a
genetic (idiopathic) epilepsy.
-Focal seizures in a neonate:
focal lesions (perinatal stroke) or

12. •Duration of seizure and state of consciousness
(retained / impaired).
•Whether an aura preceded convulsion.
•Auras - visual (e.g., flashing lights or seeing
colors),
somatosensory (tingling),
olfactory,
auditory etc.
•Most common aura - epigastric discomfort or

13. •Posture of patient,
•Cyanosis: presence or absence and
distribution
•Vocalizations,
•Loss of sphincter control (Bladder/Bowel)

14. Identify underlying cause :
•Chronic personality changes/symptoms of increased
ICP - Tumor
•H/o cognitive regression – Degenerative/Metabolic.
•H/o prenatal/perinatal distress/developmental delay
–
Congenital/Perinatal Brain Dysfunction.
•Acute/subacute personality changes, Psychiatric
symptoms, associated Movement abnormalities –
Autoimmune etiology.

15. Examination
•Head circumference, Length, and Weight.
•General and Neurologic examination.
•Fundus - Papilledema,
Optic neuritis,
Retinal Hemorrhages,
Uveitis, Chorioretinitis,
Coloboma, or Macular changes.

16. •Unusual facial features or physical findings
–
-Hepatosplenomegaly: Storage disease or
IEM.
-Presence of a Neurocutaneous Disorder:
vitiliginous ash leaf–type lesions,
adenoma sebaceum, shagreen patches

17. •Localizing neurologic signs:
hemiparesis – slow growing glioma.
•Unilateral growth arrest of thumbnail, hand, or
extremity in a child with a focal seizure
disorder: chronic condition such as
a porencephalic cyst,
arteriovenous malformation, or
cortical atrophy of opposite
hemisphere.

18. •Laboratory testing –
Serum Electrolytes,
Complete Blood Count,
Urine toxicology tests.
•Electrocardiography (ECG) - long QT or other
Dysrhythmias.
•Lumbar puncture - Infection or Intracranial
bleeding.

19. •Routine EEG in all cases of a first unprovoked
nonfebrile
seizure to predict risk of seizure recurrence.
•Brain Imaging (CT or MRI) –
-Focal seizure,
-Postictal focal deficits or patient's status is not
returning
to baseline;
-Trauma preceding the seizure; and

20. Febrile Seizures
•Occur between ages 6 and 60 months (peak 12-18
mo)
•with a temperature of 38°C (100.4°F) or higher,
•not result of CNS infection or any metabolic
imbalance,
•No history of prior afebrile seizures.

21. •Simple Febrile Seizure
-primary generalized, usually tonic-clonic for maximum
of 15
min, and not recurrent within a 24-hr period.
-Very short postictal state and return to baseline normal
behavior and consciousness within minutes.
•Complex Febrile Seizure
more Prolonged (>15 min), and/or Focal, and/or
Recurs within 24 hr.

22. • Between 2% and 5% of neurologically healthy children
experience at
least one, usually simple, febrile seizure.
• Simple febrile seizures - no increased risk of mortality.
• Complex febrile seizures - 2-fold long-term increase in mortality
rates.
• No long-term adverse effects of one or more simple febrile
seizures.

23. •Febrile seizures recur approximately:
-in 30% after first episode,
-in 50% after two or more episodes, and
-in 50% of infants younger than 1 yr of age at febrile
seizure
onset.
•only 5% (range 1–33%, dependent on risk factors) of
children
who have febrile seizures proceed to develop epilepsy

24. •Any type of epilepsy can be preceded by febrile
seizures.
•Few epilepsy syndromes typically start with febrile
seizures:
-Generalized Epilepsy with Febrile Seizures plus
(GEFS+),
-Severe Myoclonic Epilepsy of Infancy-Dravet
Syndrome
-Temporal lobe epilepsy secondary to mesial

25. Lumbar Puncture
•In all infants younger than 6 month of age
•child is ill-appearing,
•clinical signs or symptoms of concern.
•deficient in Haemophilus influenzae type b and
Streptococcus pneumoniae immunizations or
immunization status is unknown.
•pretreated with antibiotics.

26. Treatment
• Antiepileptic therapy not recommended.
• If seizure lasts for longer than 5 min - Lorazepam, Midazolam.
• Rectal Diazepam/Buccal or Intranasal Midazolam - as rescue.
• frequently recurring febrile seizures - intermittent oral
clonazepam/
Clobazam or oral diazepam during febrile illnesses.

27. Epilepsy Syndrome related to Focal Seizures
Benign Epilepsy Syndromes With Focal Seizures:
•Benign childhood epilepsy with centrotemporal
spikes
(BECTS) – Most common
•Benign epilepsy with occipital spikes
•Benign infantile familial convulsion syndromes

28. Severe Epilepsy Syndromes With Focal
Seizures:
Caused by severe metabolic problems, hypoxic-
ischemic injury, or congenital malformations.
•Mesial (medial ) temporal sclerosis,
•Rasmussen encephalitis

29. Epilepsy Syndromes Related to Generalized
Seizures
Benign Generalized Epilepsies:
•Childhood absence epilepsy
•Benign myoclonic epilepsy of infancy
•Febrile seizures plus syndrome
•Juvenile myoclonic epilepsy (Janz
syndrome)
•Photoparoxysmal epilepsy
•Reflex (stimulus provoked ) epilepsy

30. Severe Generalized Epilepsies:
Associated with intractable seizures and developmental
delay.
•Early myoclonic infantile encephalopathy.
•Early infantile epileptic encephalopathy
(Ohtahara syndrome).
•Severe myoclonic epilepsy of infancy (Dravet
syndrome).
•West syndrome
•Lennox-Gastaut syndrome.

31. •Pyridoxine dependent epilepsy
•Pyridoxal phosphate–responsive
neonatal epileptic encephalopathy
•Folinic acid–responsive seizures.
•Cerebral folate deficiency,
•Tetrahydrobiopterin deficiencies.
•Creatine deficiency syndromes.
•Biotinidase deficiency

32. Treatment of Seizures and Epilepsy
Deciding on Long-Term Therapy:
•After a first seizure,
If low risk of recurrence(20%) -
Normal neurodevelopmental status,
Normal EEG, and
Normal MRI
- treatment is usually not started.

33. • Higher Risk of Recurrence:
-Abnormal EEG,
MRI,
Development status,
Neurologic exam,
Positive family history.
often treatment is started.

34. Counseling:
•Educating family/child about disease,
management,
and limitations it impose and to deal with them.
•Restrictions on driving (in adolescents),
swimming,
and certain sports are usually necessary.
•Psychological evaluation for learning

35. •Increased risk of mortality (two or more times of
general population), sudden unexpected
death.
•Mostly related to conditions associated -
tumor,
metabolic disease,
poor seizure control,
poor compliance.

36. Choice of Drug:
Based on type of seizure and epilepsy syndrome.
Drugs of First Choice -
•Focal seizures - oxcarbazepine, levetiracetam.
•Absence seizures – ethosuximide.
•Juvenile myoclonic epilepsy – valproate.
Therapy should always be individualized.

37. •West Syndrome - ACTH/oral steroids, Vigabatrin,
valproate.
•Lennox-Gastaut Syndrome- clobazam, valproate,
lamotrigine,
Topiramate.
•Dravet Syndrome - benzodiazepines (clobazam),
valproate,
Ketogenic diet in refractory status.
•Absence Seizures - ethosuximide, valproate, lamotrigine
•Benign Myoclonic Epilepsies - valproate, clonazepam,
lamotrigine.

38. Choice of Drug: Other Considerations
◆ Potential for paradoxical seizure aggravation -
precipitation of myoclonic seizures by lamotrigine in
Dravet syndrome
exacerbation of absence seizures by
carbamazepine.
◆ Comparative tolerability:
Increased risk of liver toxicity for valproate -
-Children younger than 2 yr of age,
-Polytherapy or
-Metabolic disorders.

39. ◆ Choice also influenced by side effects -
-Weight gain (valproate, carbamazepine),
-Gingival hyperplasia (phenytoin),
-Hyperactivity (benzodiazepines, barbiturates,
-levetiracetam, valproate, Gabapentin), or
-Irritability/anger (levetiracetam and
perampanel).

40. ◆ Cost and availability
◆ Ease of initiation:
Gradual Initiation (lamotrigine, topiramate) -
Don’t achieve a therapeutic level quickly.
Quick Initiation and titration -
(levetiracetam, phenytoin, or Valproate)

41. ◆ Drug interactions:
•Valproate inhibits metabolism-
increases levels of lamotrigine,
phenobarbital.
•Enzyme inducers (phenobarbital,
Phenytoin,
carbamazepine)-

42. ◆ Comorbid conditions:
•Migraine - medication effective against both
conditions
(valproate, topiramate).
•Obesity – Avoid Valproate
Use topiramate ( decrease appetite).
• Female of child-bearing age - Avoid enzyme
inducing

43. ◆ Coexisting seizures:
Presence of multiple type of seizure –
Use Broad spectrum AED (lamotrigine or valproate),
Avoid Narrow spectrum AED
(phenytoin/ethosuximide).
◆ History of prior response to specific AEDs:
A family member with same problem responded to
carbamazepine, carbamazepine is desirable.

44. ◆ Mechanism of drug actions:
•Avoid combination with similar mechanisms of action-
phenytoin and carbamazepine (both act on sodium
channels).
•Prefer combination with different mechanism of action
(synergistic effect) –
lamotrigine plus valproate/topiramate plus lamotrigine.
◆ Ease of use: OD or BD dosing are easier than
TDS/QID.
Availability of a pediatric liquid

45. ◆ Ability to monitor the medication:
Newer AEDs generally do not require blood level
monitoring.
◆ Teratogenic profiles:
Levetiracetam/Lamotrigine (category C)- safest in
pregnancy.
Valproate (category X)- NTDs, Hypospadias, CVS
malformations.
Topiramate/Phenobarbital/Phenytoin (category D)-
Teratogenic.

46. Discontinuation of Therapy
•Seizures free for at least 2 year and a normal EEG.
•Severe Epilepsy syndromes –
Temporal lobe epilepsy due to mesial temporal
sclerosis,
Lennox-Gastaut syndrome, severe myoclonic
epilepsy -
prolonged seizure free period for AEDs withdrawal.
•Benign Epilepsy syndromes – Self limited

47. •Most relapses - within first 6 mo.
•Most important risk factor for relapse –
an abnormal EEG before AED discontinuation.
•Other factors for higher risk of relapse -
older age of epilepsy onset,
longer duration of epilepsy,
presence of multiple seizure
types,
need to use more than one

48. •AED should be discontinued gradually
(over 3-6 month).
•Abrupt discontinuation –
withdrawal seizures or status epilepticus.
•A prescription for rectal diazepam or intranasal
midazolam at the time of seizures.

49. Status Epilepticus
•Medical emergency.
•Definition:
- For GTCS -
continuous or recurrent convulsion without
regaining of
consciousness. (t1 = 5 min, t2 ≥ 30 min).
- For focal seizures with impaired awareness -
(t1 = 10 min, t2 = 30 min)
- Absence SE

50. •Most common type - convulsive SE
(generalized tonic, clonic, or tonic-clonic).
•Other Types - Nonconvulsive SE -
Focal with impaired
awareness,
Absence,
Myoclonic.
• Most common in children less than 5 yr of

51. •Approximately 30% of patients - first seizure.
•Approximately 40% of these later develop
epilepsy.
•Febrile status epilepticus - most common
type in
children.

52. •Refractory status epilepticus –
failed to respond to at least two medications.
•Superrefractory status epilepticus –
failed to resolve, or recurs, within 24 hr
despite continuous infusion such as
midazolam
and/or pentobarbital.

53. Etiology
•New-onset epilepsy of any type.
•Drug intoxication (TCAs/Alcohol).
•Drug withdrawal of AEDs.
•Hypoglycemia, Hypocalcemia,
Hyponatremia,
Hypomagnesemia.
•Acute Head Trauma.

54. •Folinic acid and Pyridoxine and Pyridoxal-
Phosphate
Dependency.
•Nonketotic Hyperglycinemia (neonates).
•Mitochondrial Encephalopathy with Lactic
Acidosis
(MELAS) in infants, children and adolescents.

55. •Systemic conditions-
Hypertensive encephalopathy,
Renal or Hepatic encephalopathy.
•Ischemic (arterial or venous) stroke,
Intracranial Hemorrhage.
•Encephalitis, Meningitis,
Autoimmune Encephalitis.

56. •Brain Tumors.
•Brain malformations, Neurodegenerative disorders,
Storage diseases.
•Infections, Encephalitis, Herpes simplex, EBV.
•Acute Disseminated Encephalomyelitis.

57. Management
•Secure Airway, Breathing, and
Circulation.
•Determine and manage underlying cause
(hypoglycemia).
•Laboratory studies
Glucose, Sodium, Calcium, Magnesium, CBC,
Blood/CSF

58. •EEG –
Rule out pseudo–status epilepticus -
-Psychological conversion reaction
mimicking
SE)
-Movement disorders (chorea, tics), rigors,
decerebrate/decorticate posturing.
•Neuroimaging – after stabilization.

59. Initial Emergent Therapy –
•Benzodiazepines (1st Line)-
i/v lorazepam,diazepam, i/m midazolam.
•Buccal or intranasal midazolam, intranasal
lorazepam, or
rectal diazepam.
•Respiratory depression - potential side effect.

60. Urgent Therapy -
•In case of unsuccessful Emergent therapy
(persistent seizures 5 min after 2nddose of
benzodiazepine) –
Phenytoin, Valproate, Levetiracetam.
Seizures persist after urgent therapy -
•Another second-line agent or proceeding to
a

61. Refractory status epilepticus
•Continuous infusion –
Midazolam, Propofol, Pentobarbital, or
Thiopental.
•Goal –
stop electrographic seizure activity before
reducing therapy.
•Careful attention to BP, systemic complications

62. •Midazolam - fewer side effects but less
effective,
•Barbiturate coma - more effective but higher
risk of
side effects.
•Propofol –
propofol infusion syndrome with lactic acidosis,
hemodynamic instability, and rhabdomyolysis
with

63. •Treat underlying cause-
Immunotherapy in anti-NMDA receptor
encephalitis.
•Unclear etiology –
Immunotherapy (steroids, immunoglobulins,
plasma exchange).
•Ketamine infusion –(NMDA receptor

64. •Hypothermia.
•Lesional SRSE -
Hemispherectomy for Rasmussen
encephalitis,
Focal resection (area of cortical dysplasia).
•Vagal nerve stimulation,
•Electroconvulsive therapy,
•Transcranial magnetic stimulation.
•Allopregnanolone (neurosteroid).

65. Thank You!