FEBRILE SEIZURE

Dewi Sutriani Mahalini

Neuropediatric Division
Department of Child Health
Medical Faculty of Udayana University/Sanglah Hospital
 Seizure
Definition:
a sudden temporary change in brain function caused by
an abnormal rhytmic electrical discharge
due to the releasing of excessive electric load from
deteriorated neurons cells in the brain
Can caused by disturbance of:
Physiological
Anatomical
Biochemical
Combination of the above component
 Seizure medical emergency
Have to be managed quickly &
appropriately
Mechanisme of Seizure

Partial secondary
generalized

Focal seizure General seizure

mechanisme

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Definition
Defined by The International League Against Epilepsy
(ILAE)
Febrile seizure:
a seizure occurring in childhood after one month of age,
associated with a febrile illness not caused by an infection
of the central nervous system, without previous neonatal
seizures or a previous unprovoked seizure, and not meeting
criteria for other acute symptomatic seizures

Jones T, Jacobsen SJ. Childhood Febrile Seizures: Overview and

Implications. Int. J. Med. Sci. 2007, 4 (2):110-14
Definition
Febrile Seizure is a seizure in childhood,
usually occurring assosiated with fever (>380C
rectal) but without evidence of intracranial
infection or define cause.
Seizure with fever in children who have
suffered a previous non-febrile seizure are
excluded.
Ismael S, KPPIK XI, 1983;
Soetomenggolo TS. Buku Ajar Neurologi Anak 1999

6
Natural history
Most febrile seizures occur between 6
months and 36 months of age peaking
at 18 months
The occurrence of a childs first (initial)
febrile seizures has been associated with:
first or second-degree relative with
history of febrile and afebrile seizures
 PATHOPHYISIOLOGY
Remain unknown
It is possible that 3 feature interact
resulting in a febrile seizure:
1. Immature brain
2. Fever
3. Genetic predisposition

Carney PR. Pediatric Practice Neurology, 2010

Immature brain
FS rarely occur before 1-3 mo certain
degree of myelination/ network
maturation is required for clinical
expression of FS
FS rarely occur after 5-6 years
Enhanced neuronal excitability during
normal brain maturation

Carney PR. Pediatric Practice Neurology, 2010

FEVER
Fever associated with cytokine release
Activation of cytokine release may
increase the susceptibility to FS
IL-1( a pyrogenic proinflamatory
cytokine) involved in generation of FS
Temperature changes affect plasma
membrane states & synaptic transmission

Carney PR. Pediatric Practice Neurology, 2010

 FEVER....
Responsible for occurrence of fever in febrile convulsion:
respiratory tract infection
gastro enteritis
urinary tract infection
roseola infantum
post immunizations

The degree of temperature:

75% of children had temperature >38oc
25% of children had temperature > 40oc
Genetic factors
Genetic factors play an essensial role in the
genesis of FS.
Although there is clear evidence for a
genetic basis of FS, the mode of inheritance
is unclear
The risk of developing FS is higher in some
families than in others (25-40 %)
Genetic loci for FS
Chromosome 2q, 19q SCN1A, SCN1B,
SCN2A gene

Carney PR. Pediatric Practice Neurology, 2010

TYPE OF FEBRILE SEIZURE

SIMPLE FEBRILE SEIZURES

COMPLEX FEBRILE SEIZURE
FEBRILE SEIZURE PLUS

ILAE, Commission on epidemiology & prognosis.

Epilepsia 1993
 CLASSIFICATION...

Simple febrile seizures: consist of

A brief (lasting <15 minutes)
Generalized seizure tonic-clonic ) or
there are no focal features and it
resolves spontaneously
Which occurs only once within a 24
hour period.

American Academy of Pediatrics Practice.

Pediatric Neurology Working Groups
 CLASSIFICATION...

Complex febrile seizures

Prolonged ( Duration > 15 minutes),
Focal
Occuring in a cluster of 2 or more
convulsions within 24 hours (recurrent
within the same febrile illness over a 24-hour
period).

American Academy of Pediatrics Practice.

Pediatric Neurology Working Groups
Febrile Seizure Plus (Fs+)
FS continous until >6 years old
FS > 13 times/ years
History : seizure without fever
previously FS

FS+ Intra-familial & Epilepsy

inter-familial

Scheffer IE, et al. Brain 1997;120:479-90.

GEFS+
Baulac S, et al. Lancet Neurol. 2004;3:421-30.
Panayiotopoulos CP.The epilepsies.2005. h128-30.
 INCIDENCE FS
Simple febrile seizures : 70-75%
Complex febrile seizures : 9-35%

Jones T, Jacobsen SJ. Childhood Febrile Seizures: Overview and

Implications. Int. J. Med. Sci. 2007, 4 (2):110-14
 INCIDENCE.....
National Collaberative Perinatal Project Study:
74% of initial febrile seizure were simple
26% of the initial febrile seizure were complex
4% focal
8% prolonged greater than 15 minutes
16% with recurrence within 24 hours
0.4% with Todd paresis

Carney PR. Pediatric Pratice Neurology.2010

RISK FACTORS FOR FIRST FS

The risk of a 1st FS is about 30% if have >2

risk factor below:
A first or second degree relative with FS
Delayed neonatal discharged of greater
than 28 days of age
Parental report of slow development
Predictors of recurrent febrile
seizures
A history of focal, prolonged, and multiple
Seizures
Family history of febrile seizures
onset of febrile seizure <12 months of age
temperature <40C (<104 F) at time of seizure
a history of complex, initial febrile seizures

Jones T, Jacobsen SJ. Childhood Febrile Seizures: Overview and

Implications. Int. J. Med. Sci. 2007, 4 (2):110-14
Chung et al. Febrile seizures in Chinese children. j. pediatrneurol. 2005.08.007
 DIAGNOSIS
The diagnosis of FS is not always easy
Acute febrile encephalopathy, encephalitis
and meningitis
Febrile shivering (peribuccal cyanosis)
Febrile delirium that associated with
agitation
Syncope or reflex anoxic seizure, also can
be triggered by fever.

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 Differences Between
FS & Seizures due to Febrile Brain Diseases.
Febrile seizure (FS) Seizure and fever in brain
disease
Genetic predisposed to May be strong Mostly minor or insignificant
seizure
Type of seizure Tonic-Clonic Focal or focal -generalized
Duration of seizure Mostly 1-3 min1 Often prolonged, 10 min to
seldom prolonged hours (status like)
Clinical setting which seizure in at the onset of a febrile In a variety of CNS infections
occure
Type of underlying cerebral None Various types of inflammatory
pathology vascular changes and edema
Postictal neurologic Very uncommon Common
(Todds paralysis Conscious
EEG Rapidly normalizes after Abnormal throughout febrile
convulsion episode

Niedermeyer E. Epilepsy Guide: Diagnosis and Treatment of Epileptic Seizure Disorders , 1985
Work up child with FS
1. Hospitalization (rarely nescessary)
complex FS
2. Evaluation cause of fever
3. Lumbar puncture
Strongly consider: infant < 12 months
Should be consider: children between 12-18 mo
Not routinely : beyond 18 mo
4. EEG : not necessary since non predictive of
recurrence / epilepsy later
RCP / BPA, 1991. AAP, 1999. Fukuyama Y, 1996. Baumer J.2004.
MANAGEMENT OF FS

1. Prevention of prolonged seizure

2. Intermittent prophylaxis
3. Continuous prophylaxis

25
 % cease
spontaneously

Seizure
duration
10 minutes

Probability of a seizure ceasing spontaneously decreases

rapidly after 10 minutes
FEBRILE STATUS EPILEPTICUS
Prolonged fits cause progressive cerebral
hypoxia, cerebral oedema, lactic acidosis
and further excitotoxicity
25% of status epilepticus in children
40% of the time of the first seizures.
2/3 of children who are neurological
abnormal will have further FS. 1/3 risk
another episode of status.
Daoud A. 2004

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DRUG DOSES
Table.
DRUGS USED TO TERMINATE STATUS
EPILEPTICUS

Drug Onset of Action Duration of action Maximal Rate

Diazepam 1-3 minute 5-15 minute < 2 mg/min

Midazolam 2-5 minute 30-60 minute < 2 mg/min

Phenytoin 10-30 minute 12-24 hours < 1 mg/kg/min

< 50 mg/min

Phenobarbital 10-20 minute 1-3 days < 1 mg/kg/min

< 100 mg/min

Freedman SB. Clin Pediatric Emergency Medicine,2003

Emergency Drugs
INTERMITTENT PROPHYLAXIS

Rectal or oral diazepam

Intermittent diazepam prophylaxis seems to be
effective in reducing the recurrency rate.
Doses for prophylaxis whenever temperatur
> 38,50 C : 0,3 mg/kg orally, or 0,5 mg/kg
rectally every 8 hours
Parents should be advised not to give rectal
diazepam if the seizure has stopped.

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CONTINOUS PROPHYLAXIS

Meta analysis of 47 controlled trials found

that phenobarbitone halved the risk of
recurrence of FS
Phenobarbitone and valproate had
significantly lower risk of recurrence than
those on plasebo.
Recurrence rate of 12.8% with valproate,
13% with phenobarbital, and 34% in
untreated controls

Wallace and Aldridge-smith 1981, Rantala et al, 1997. Temkin 2001.

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CONCENSUS 2005
Daily
continuous anticonvulsant (one or
more)
The presence of an abnormal neurologic (CP, MR,
Microcephaly)
History of prolonged febrile seizure (>15 min)
History of focal seizure
Consider daily continuous anticonvulsant
Multiple febrile seizure ( 2 or more within 24 hours)
Seizure occur under the age of 12 months
Frequent seizures (4 or more times in 12 mo)
NIH, 1980. Ismael S, 1983. Fukuyama Y, 1996

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PROGNOSIS
Normal children most children
Epilepsy : 2-4%, (3% on average)
4-6 times higher than the incidence of
epilepsy in the general child population
Learning & behaviour disorder
(uncommon)
Diskinesia & Incoordination(uncommon)
Mental Retardation (rarely)
Risk of developing epilepsy after FS based
on asscociated factors

Positive family
history 5.3% Abnormal
10% Development
3.3%

23%

13% 18%

Complex febrile
seizure 4.1%

Nelson KB, Ellenberg JH: Prognosis in children with febrile seizures.

Pediatrics 61:1978
Epilepsy following FS
The risk of later epilepsy is higher when :
The child had been developmentally
abnormal prior to first seizure
The first seizure was long, lateralized, or
repeated during a single febrile episode.
Complex FS
A first - degree relative with epilepsy

Aicardi, 1994
 The risk of initial febrile seizures has also
been studied after receipt of pediatric
vaccinations DTP and Measles, MMR
2-4% of children who experience at least
one febrile seizure event go on to
develop recurrent afebrile seizures
(epilepsy)
 PATHOPHYISIOLOGY
Animal models demonstrated:
age specific susceptibility to seizure induced by
fever.
Febrile seizure begin in the hippocampus or
amygdala.
Seizure lasting less than 10 minutes are not
associated with any anatomic or functional
changes.

Maria BL. Current management in child neurology, 2009.

PATHOPHYISIOLOGY
The results suggest that preexisting CNS
anomalies may make the brain more
susceptible to prolonged seizures and to
seizure induced injury.

Maria BL. Current management in child neurology, 2009.

RISK FACTORS FOR FIRST FS

The risk of a 1st FS is about 30% if have >2

risk factor below:
A first or second degree relative with FS
Delayed neonatal discharged of greater
than 28 days of age
Parental report of slow development
 Recurrence of Initial FS and Its Risk Factors

(1) Recurrence rate Second : 25 50% (30% on average)

Third or more : About 9%
(2) Risk factors for recurrence
1) Age of onset : Recurrence is more common at lower ages
2) Sex : Female > Male
3) Family history : Incidence is higher in children with a family
history of this disease.
4) Neurological abnormalities and developmental disorders prior
to the onset.
(3) Timing of recurrence
Within 6 months after the initial onset : 50%
Within one year after the initial onset : 75%
Within two years after the initial onset : 90%

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 The risk of initial febrile seizures has also
been studied after receipt of pediatric
vaccinations DTP and Measles, MMR
2-4% of children who experience at least
one febrile seizure event go on to
develop recurrent afebrile seizures
(epilepsy)