an outlook on seizures in childhood

1. SEIZURES IN PEDIATRICS
BY:TASNEEM ABDUL GAFOOR
PHARM D intern

2. INTRODUCTION
 SEIZURES
-Seizures are sudden uncontrolled abnormal electrical activity of neurons situated in the
cerebral cortex.
It can cause changes in your behavior,movements or feelings and in level of consciousness.
-If manifests as motor act – “convulsions”
 EPILEPSY
Epilepsy is defined as Chronic neurological disorder characterized by recurrent unprovoked
seizures, associated with abnormal,excessive or synchronous neuronal activity in brain

3. ETIOLOGY
 Idiopathic (70-80%)
 Cerebral malformations
 Cerebral vascular occlusion
 Cerebral damage (ex; congenital infections, hypoxic-ischaemic encephalopathy)
 Cerebral tumour
 Neurodegenrative disorders(Neurofibromitosis etc)
 Metabolic causes
 Head trauma.
 Meningitis/encephalitis
 Poisons/Toxins

4. TYPES

5. FOCAL SEIZURES
 Pediatric focal seizures take place when abnormal electrical brain function occurs
in one or more areas of one side of the brain.

6. GENERALIZED SEIZURES
 Generalized pediatric seizures involve both sides of the brain.
 There is loss of consciousness and a postictal state after the seizure occurs.
1.ABSENCE SEIZURES
 Pediatric absence seizures (also called petit mal seizures) are characterized by a
brief altered state of consciousness and staring episodes.
 Typically the child's posture is maintained during the seizure. The mouth or face
may move or the eyes may blink.
 The seizure usually lasts no longer than 30 seconds.
 When the seizure is over, the child may not recall what just occurred and may go
on with his/her activities, acting as though nothing happened.
 These seizures may occur several times a day..
 Absence seizures almost always start between ages 4 to 12 years.

7. 2.ATONIC SEIZURES
 With atonic seizures in children (also called drop attacks) there is a sudden loss of
muscle tone and the child may fall from a standing position or suddenly drop
his/her head.
 During the seizure, the child is limp and unresponsive.
3.GENERALIZED TONIC-CLONIC SEIZURES
 This seizure (GTC or also called grand mal seizures) is characterized by five distinct
phases that occur in the child.
 The body, arms, and legs will flex (contract), extend (straighten out), tremor
(shake), a clonic period (contraction and relaxation of the muscles), followed by
the postictal period.
 During the postictal period, the child may be sleepy, have problems with vision or
speech, and may have a bad headache, fatigue, or body aches.

8. 4.MYOCLONIC SEIZURES
 This type of seizure refers to quick movements or sudden jerking of a group of
muscles.
 These seizures tend to occur in clusters, meaning that they may occur several
times a day, or for several days in a row.
INFANTILE SPASMS
 This rare type of seizure disorder occurs in infants from before six months of age.
 There is a high occurrence rate of this seizure when the child is awakening, or
when they are trying to go to sleep.
 The infant usually has brief periods of movement of the neck, trunk, or legs that
lasts for a few seconds.
 Infants may have hundreds of these seizures a day and can be a serious problem.

9. FEBRILE SEIZURES
 Pediatric febrile seizures are associated with fever.
 Febrile seizures most often occur within 24 hours of the onset of a fever and can
be the first sign that a child is ill.
 The fever may accompany common childhood illnesses such as a cold, the flu, or
an ear infection. In some cases, a child may not have a fever at the time of the
seizure but will develop one a few hours later.
 These seizures are more commonly seen in children between 6 months and 5
years of age and there may be a family history of this type of seizure.
 Febrile seizures that last less than 15 minutes are called "simple," and typically do
not have long-term neurological effects.
 Seizures lasting more than 15 minutes are called "complex" and there may be
long-term neurological changes in the child.

10. STATUS EPILEPTICUS
A seizure that lasts longer than 5 min or having more than 1 seizure within a 5 min
period without returning to the normal level of consciousness between the episodes.
TREATMENT FOR FEBRILE SEIZURE
Appropriate posturing (lateral recumbent, with head extension), and keeping
airways open are the recommended maneuvers for the affected children.
Rectal diazepam is a good and reliable way to control seizures outsides of the
hospital and even at home.Also intrabuccal and intranasal midazolam is used to
control seizures
When a child comes to emergency room with seizure, an IV route should be
obtained and intravenous diazepam should be administered.
There is not enough evidence that antipyretics would reduce the risk of seizures in
a febrile illness.

11. It is recommended to use oral diazepam in a dose of 0.33 mg/kg/dose every 8
hours from the onset of a febrile illness.
Some studies indicating that intermittent clobozam could be as effective as
diazepam in preventing the seizures in a febrile illness.
 Intermittent administration of phenobarbital is ineffective in preventing the
febrile seizures.
 The use of phenobarbital (5 to 8 mg per kg of weight per day for children two to
24 months of age, and 3 to 5 mg per kg per day for children older than two
years) and valproic acid (10 to 15 mg per kg per day in divided doses, on a
continuous basis reduces the risk of recurrent febrile seizures.

12.  Although valproic acid (Depakene), diazepam (Valium), lorazepam (Ativan), and
fosphenytoin (Cerebyx) are indicated for the management of seizures, they have
not been indicated explicitly for the management of febrile seizures.

14. TREATMENT FOR STATUS EPILEPTICUS

16. FIRST-GENERATION ANTIEPILEPTIC DRUGS (AEDS)
 Carbamazepine (CBZ) Is the first-line and adjunctive therapy for treatment of
focal seizures (FS) and generalized tonic–clonic seizures (GTCS)
 Clobazam (CLB )is currently approved for use as an AED in more than 100
countries. CLB was approved for adjunctive treatment of Lennox-Gastaut
syndrome (LGS) in patients aged 2 years or older.
 According to the NICE guidelines, the use of Clonazepam (CZP) in patients with
absences and myoclonic seizures is recommended when first-line drugs are
ineffective or not tolerated .
 ACTH was as effective as high-dose prednisolone in reducing spasms and more
effective in reducing EEG abnormalities. Low-dose ACTH or prednisolone should
be considered for treatment of cryptogenic infantile spasms
 Ethosuximide ETS was approved as first-line and adjunctive therapy for treatment
of generalized absence seizures.

17.  PB is approved as adjunctive and first-line therapy for treatment of FS and
generalized seizures, including myoclonus but not absences.
 PHT was approved as first-line and adjunctive therapy for treatment of FS and
generalized seizures, except myoclonic and absence seizures.
 VPA was first approved as first-line and adjunctive therapy for the treatment of
generalized epilepsies
SECOND GENERATION AEDS
 FBM was initially approved by the FDA as add-on treatment of LGS and focal and
secondary generalized seizures in patients refractory to other agents.
 GPT was approved by the FDA as adjunctive therapy in the treatment of FS, with
or without secondary generalization, in adults and p ediatric patients 3 years and
older
 LTG should be considered as a first-line drug for FS and GTCS. LTG, as monotherapy
or in add-on, represents an alternative treatment for absence seizures if ETS and
VPA are unsuitable, ineffective or not tolerated

18.  LEV can be used in patients from 16 years of age with newly diagnosed epilepsy
to treat FS with or without secondary generalization.
 OXC was approved as adjunctive therapy for children ages 4–16 years with FS.
 TPM is now also indicated as initial monotherapy in patients 2 years of age and
older with FS or primary GTCS.
 ZNS is used as an ‘add-on’ therapy for FS in adults and children aged 6 years and
above already receiving other AED

19. PHARMACOLOGICAL THERAPY
VALPROATE SODIUM
DOSE:
 Childrens and adolscents
Initial-10-15mg/kg/day in 1-3 divided doses.
Maintenance-30-60mg/kg/day in 2-3 divided doses.
MOA-Increases the availability of GABA or enhance its action,blocks voltage gated Na
channels resulting in suppression of high frequency neuronal firing.
PK
Metabolism- hepatic
PB-80-90%
Excretion- urine
Half life-7Hrs(>2mo);9hrs(2-14 yr)

20. CARBAMAZEPINE
CATEGORY; Voltage gated Sodium channel blocker.
DOSE
 monotherapy or adjunct
 < 6 years old
10 mg/kg to 20mg/kg/day in 2 or 3 divided doses
MAX-35 mg/kg/day.
 6 to 12 years old
100 mg twice a day (tablets) or 50 mg 4 times a day (suspension)
MD-400-800 mg/kg/day in 3-4 divided doses.
MAX-1000 mg per day.
 >12Years old
200 mg twice a day (tablets) or 100 mg 4 times a day (suspension)
MD-800-1200mg/kg/day in 3-4 divided doses.
MAX-1000 mg per day; Older than 15 years old: MAX-1200 mg per day.
MOA-. It binds preferentially to voltage-gated sodium channels, which prevents repetitive and
sustained firing of an action potential.

21. PK
 Elimination half-life: 34 hours (single dose), 16-24 hours (repeated dosing)
 Metabolism: Hepatic—by CYP3A4, to active epoxide form (carbamazepine-10,11
epoxide)self Inducer
 Bioavailability:~100%
 Excretion-Urine
LAMOTRIGINE
DOSE
 Adjuvant therapy
 <2 years(receiving non enzyme inducing AED)
WK1&2-0.15mg/kg/day ;WK3&4-0.3mg/kg/day
Maintenance dose -increase dose every week NMT 0.3mg/kg/day
Pt receiving enzyme inducing AEDs.
WK1&2-O.6mg/kg/day ;WK3&4-1.2mg/kg/day
Maintenance dose- increase dose every week NMT 1.2mg/kg/day

22.  2-12 years (pt receiving non enzyme inducing AED )
Wk1&2-0.3 mg/ kg/day ;WK 3&4-0.6mg/kg/day
round calculated dose to the nearest whole tablet.
Usual MD-4.5-7.5mg/kg/day in 2 divided doses.
Max-300mg/day
(Pt receiving Enzyme inducing AEDS)
WK1&2-O.6mg/kg/day ;WK3&4-1.2mg/kg/day
Maintenance dose- increase dose every week NMT 1.2mg/kg/day
 >12 years(pt receiving non enzyme inducing AED )
WK1&2-25 mg once a day;WK3&4-50mg OD
MD-increase every 1-2 wk by 50mg/day
Max-375 mg/day in 2 divided dose
(Pt receiving Enzyme inducing AEDS)
WK1&2-50 mg/day; WK3&4-100mg/day in2 divided doses.
MD-increase every 1-2 wk by 100mg/day(usual MD:300-500mg/day)

23. MOA -It inhibits the release of Glutamate and inhibits the voltage sensitive sodium
channels which stabilizes neuronal membranes.
PK:
Protein binding-65%
Metabolism- liver(substrate of UGT1A4)
Excretion- Renal.
LEVETIRACETAM
DOSE:
 6 years old to younger than 16 years old
Initial-10 mg/kg/dose In 1-2 divided doses
Increase every 2 wk by 10-30mg/kg/day (MAX- 60mg/kg/ day)
 16 years old and older
Initial-500 mg twice a day.
MAX- 1500 mg twice a day.

24. MOA-Inhibition of voltage dependent N-type calcium channels,facilitation of GABA-ergic
inhibitory transmission by binding to synaptic proteins SVP2A which modulate NT release.
PK:
Protein binding-<10%
Metabolism- enzymatic hydrolysis
Excretion- Renal.
Half life-5-7hrs
BA-100%
TOPIRAMATE
 Monotherapy.
 2 -10 years old
Initial-25mg OD
MD-increase by 25mg BD week 2nd,then 25-50mg/day

25.  >10 years
Initial-25mg OD
MD-increase weekly intervals by 50mg/day upto 100mg BD.
MAX- 200 mg twice a day.
 adjunct therapy
 2 years old to 16 years old
Initial-1 mg per kg to 3 mg per kg/day for week at night.
MD-increase to a target dose of 6mg/kg/day in 2 divided doses.
MAX- 25 mg once a day
 17 years old and older
25 mg to 50 mg per day for a week.
MD-100--200mg BD
MAX- 1600mg/day.
MOA-combination mechanism:blocks neuronal voltage gated sodium channels,enhances
GABA actibvity,antagonizes AMPA/Kinate glutamate receptors.

26. PHENYTOIN
DOSE
Initial-15-20mg/kg in 3 divided doses.
MD-5mg/kg/day in divided doses.
MAX-300 mg per day.
MOA-Stabilizes the neuronal membranes and decreases the seizure activity by decreasing
influx of Na ions across the cell membranes in motor cortex during generation of nerve
impulse.
PK
Onset-0.5-1 hr
Metabolism- hepatic
PB-80-85%
Excretion- urine
Half life-7-42Hrs