Validity of future risk prediction of electroencephalography (EEG) in complex febrile seizures.

Febrile seizures are seizures provoked by fever. This in contrary to epilepsy,
which involves unprovoked seizures. Febrile seizures affect 2-4% of children in
Europe, and are the most common form of seizures encountered in children. The
International League Against Epilepsy defines a febrile seizure as *a seizure
in association with a febrile illness in the absences of a central nervous
system (CNS) infection or acute electrolyte imbalances in children older than 1
month of age without prior afebrile seizures*. The temperature associated with
the febrile illness must be greater than 38.4 degrees Celsius, within 24 hours
before or after the seizure. Febrile seizures are most common between 6 months
and 5 years.

Febrile seizures can be classified as simple or complex. Simple febrile
seizures have no focal features, are short in duration, at least less than 15
minutes, and occur once per 24 hours in a neurologically and developmentally
normal child. Complex febrile seizures are seizures that either suggest a focal
nature, have a duration of more than 15 minutes, or occur more than once in a
period of 24 hours. After experiencing a febrile seizures, the risk of
recurrence is elevated compared to the risk in children with no history of
febrile seizures (i.e. 30%). After a simple febrile seizure, the risk of
developing unprovoked seizures (epilepsy) is not elevated, and development is
not interfered. For this reason, these seizures are named benign. Children with
complex febrile seizures have a greater risk for development of epilepsy
(4-12%)6 and delayed neurocognitive development.

A child with a simple febrile seizure usually does not need to be hospitalized
and most children with simple febrile seizures will not be seen by a
pediatrician or child neurologist. Despite its excellent prognosis, and its
lacking need of future diagnostic evaluations, it is a cause of high anxiety
among parents. In a study of Kolahi and Tahmooreszadeh in 20088, it was found
that parental fear of febrile convulsions has serious negative consequences
affecting daily familial life. It is not sure but plausible that counseling
will improve quality of life of parents after the first convulsion. However, it
is uncertain whether this group receives adequate counseling.

Most children with complex febrile seizures will be transferred to a hospital
to evaluate cause, to exclude a CNS infection and to manage follow up. It is
common to recommend an electroencephalography (EEG) for children with complex
febrile seizures, to identify the nature of the underlying acute or remote
cerebral pathology and to predict the risk of future seizures. However, limited
evidence is available to guide future diagnostic evaluations. In a recent
Cochrane review by Shah et al. in 2014, it was found that no evidence exists to
support or refute the use of an electroencephalography after complex febrile
seizures among children. Whether or not a child with a complex seizure will
undergo an EEG, cerebral imaging or future follow up of development is a
doctor*s personal choice and might be based on personal experiences.

We plan to do a trial to investigate the rationale of EEG in children with
complex febrile seizures. Because the results of EEG are sometimes used to
guide antiepileptic drug prescription (which is a potential confounding
factor), we aim to do a double blind controlled trial. Two groups are compared.
One group with the results of the EEG blinded and one group of children with
the results of the EEG open. By comparing these two groups, we can answer the
question: does performing an EEG lead to more treatment, but furthermore we can
answer the question of the rationale of EEG two years after follow up, when we
will open the results of EEG.
Furthermore, we will assess the impact of complex febrile seizures on the
quality of life and on neurocognitive and motor development.

Primary objective of this study is to investigate whether EEG can be used to
predict future febrile or afebrile convulsions.

Secondary objectives of this study are to investigate the influence of EEG on
antiepileptic drug prescription (will performing an EEG lead to more
anti-epileptic drug prescription). Furthermore whether complex febrile seizures
have impact on daily familial life using Infant Toddler Quality of Life
QuestionnaireTM (ITQOL) 10 and the impact on neuropsychological and motor
development using WPPSI and Bayley-III-NL scores. Finally we will investigate
the influence of antiepileptic drug on quality of life, neurocognitive and
motor development.

All patients with a first complex febrile seizure admitted to the hospital or
visiting the outpatients clinics (Atrium-Orbis locations Sittard and Heerlen)
will be asked to participate in this study. Patients and parents will be given
a period of 48 hours to decide whether or not they want to participate. The
inclusion period will be 2 years. The follow up period will be 2 years.

All patients will be seen by one of the doctors of the project team. A detailed
history will be taken from parents, including perinatal details, family history
details, medication, neuropsychological development. A complete neurological
and general internal examination will be performed and patients* height, weight
and head circumference and blood pressure will be measured.

In general, patients with a complex febrile convulsion will be admitted to the
hospital in order to monitor the patient for one or a couple of days, depending
the condition and/or fear of parents. Parents of all patients will be asked to
fulfill a questionnaire regarding the impact of the seizure. This will be
performed within 48 hours of the seizure.

Because the results of EEG are sometimes used to guide antiepileptic drug
prescription (which will influence the future risk of febrile and afebrile
convulsions, and is thus a potential confounding factor), we aim to do a double
blind controlled trial: patients will be randomly assigned to either the group
with the results of the EEG blinded for the doctor and the patients or the
group of children with the results of the EEG open (so the doctor and the
patient will be informed about the results).

By comparing these two groups, we can answer the question: does performing an
EEG lead to more prescriptions of anti-epileptic drugs (which will influence
our outcome parameters namely future febrile and afebrile convulsions), but
furthermore we can answer the question of the rationale of EEG two years after
follow up, when the results of the EEG*s will be revealed and all EEG*s will be
used for analysis.

Patients of both groups will undergo an early EEG (within the first week after
the seizure) and a late EEG (3 months after the seizure).

After 1, 6, 12 and 24 months children will be seen at the outpatients clinic.
Health-related quality of life and its impact on everyday functioning and
well-being will be evaluated using ITQOL assessed after 6,12 and 24 months.
Furthermore, neuropsychological, motor, and language development will be
assessed in the first month of presentation and after 2 years by using the
Bayley Scales of Infant Development-third Edition-Dutch edition (
Bayley-III-NL) for children between 6-30 months at presentation and the WPPSI
(Wechsler Preschool and primary scale of intelligence) for children between 30
months till 7 years.

The only intervention is EEG. It is not sure whether or not EEG now routinely
performed in children with complex febrile convulsions is of any benefit. If it
might not predict future epilepsy, it might not be routinely performed. This is
beneficial from point of view of the health costs and the patients burden, and
furthermore may lead to less prescriptions of anti-epileptic drugs (with less
medication related side effects).
*