ARTICLE
Auteur(s) : Gretchen L
Birbeck1,2
1Michigan State University, Associate Professor &
Director, International Neurologic & Psychiatric Epidemiology
Program (INPEP), #324 West Fee Hall, East Lansing, MI 48824,
USA
2Chikankata Hospital, Consultant and Director,
Epilepsy Care Team (ECT), Private Bag S2, Mazabuka, Zambia
Febrile Seizures–Clinical Definition
Febrile seizures are a well-recognized clinical entity specific to
children and involve seizure activity precipitated by pyrexia. As
will be discussed further, specific age delineations for febrile
seizures are somewhat vague, though for research purposes, the
1-5-years age range is often used. The key feature of the febrile
seizure is that the fever itself is presumed to be the underlying
cause for the convulsion rather than any direct effect of the
fever-inducing infection on the central nervous system (CNS).
Furthermore, a seizure occurring in a febrile child with
pre-existing epilepsy or a prior unprovoked seizure is not to be
considered a febrile seizure but should be considered a seizure
related to the underlying primary CNS predisposition to seizures
that was precipitated by the fever (Sperber et al., 1999).
Febrile seizures are categorized into two types: complex or
simple. Classification is important as there are different
long-term prognoses associated with each, and the clinical approach
to acute management may also differ by febrile seizure subtype.
Simple febrile seizures
A simple febrile seizure is characterized by a brief (usually
seconds to a few minutes,
certainly < 15 minutes), generalized seizure
associated with a fever which does not recur during the index
febrile illness.
Complex febrile seizures
Febrile seizures are categorized as complex if the seizure is
prolonged (> 15 minutes), recurrent within the same
febrile episode, or if it has any focal features. Note that in the
presence of any one of these features, the febrile seizure should
be considered complex. The presence of focality can be
characterized by the clinical seizure semiology as reported by
witnesses, but may also be evident on examination if the child has
a transient focal neurologic abnormality indicative of the Todd's
paralysis phenomena.
The Pathophysiologic Mechanisms of Febrile Seizures
Febrile seizures represent an age-dependent susceptibility to CNS
hyperexcitability and subsequent seizure when exposed to fever.
This age-dependent susceptibility is likely related to the
intrinsic excitable state of the pediatric/developing brain
relative to the adult brain. The distribution of excitatory
neurotransmitters and circuitry is more extensive in the pediatric
brain and the distribution of neurotransmitter subtypes differs in
the developing nervous system, with more excitatory pathways
active, especially in the limbic region. Furthermore,
neurotransmitters, which behave as inhibitory actors in the adult
brain, may have different characteristics in the pediatric brain
due to either receptor distribution or neurotransmitter subtypes
(Fukuda et al., 1997). There are likely important evolutionary
reasons why the developing brain exists on the cusp of
hyperexcitability — this state may be more optimal for the
neuronal plasticity needed to facilitate the intense learning
associated with early childhood (acquisition of language, etc.).
The consequence, however, is that when challenged with a fever,
children with a predisposition to this temperature-dependent
hyperexcitability may experience a dysfunctional response —
i.e. a seizure.
Additional contributing factors perhaps more common in tropical
settings have been hypothesized, including zinc deficiency (Ganesh
and Janakiraman, 2008). Zinc is the abundant trace element and is
important in the production of GABA. Whether zinc levels decisively
play a role in seizure susceptibility remains unclear.
Febrile Seizures: Diagnostic and Classification
Conundrums
As clinicians, we seek to know what treatments will offer our
patients the best immediate response and, especially in children,
whether any treatment will improve their long-term outcomes.
Unfortunately, our understanding of the natural history of tropical
febrile seizures and the impact of different management strategies
is compromised significantly by the lack of population-based,
longitudinal data delineating the etiology, semiology and natural
history of febrile seizures in tropical environments. Most data
regarding febrile seizure in the tropics has been acquired from
clinic- or hospital-based samples of children who are brought to
medical attention. In resource-limited, tropical settings where
parents face logistic, geographic and financial barriers to
care-seeking for their children, an otherwise healthy child who
experienced a brief seizure in the setting of a febrile illness is
usually not brought in for care (Chomba et al., 2008; Izuora
and Azubuike, 1977). Therefore, the children who are brought for
care are not representative of the overall population of children
with febrile seizures and may be expected to reflect the more
extreme end of the clinical spectrum in terms of seizure severity
and/or duration. The clinical and epidemiologic aspects of febrile
seizures have been well described in studies conducted in the US
and the UK, primarily birth cohort studies, which identify a
population-based age cohort of children for periodic prospective
assessment. Extrapolating the findings from US and UK studies to
tropical settings is problematic for several reasons (table 1).
Certain infections specific to the tropics may directly affect
the CNS without causing a typical meningitis or encephalitis. For
example, uncomplicated malaria can cause fever but cerebral malaria
involves cerebral sequestration with parasitized red blood cells
with subsequent coma and frequent seizures. The cerebrospinal fluid
of a child with cerebral malaria is unremarkable and does not
reflect the CNS infection, which remains intravascular. If a child
has a malarial fever and a seizure, the question arises “Is this a
febrile seizure or does this signify CNS involvement with a forme
fruste of cerebral malaria?” Clinically, cautious management in
such cases is indicated with care provision appropriate for CNS
involvement and/or close clinical observation to assure
recovery.
Since many tropical settings are also resource-poor regions, it
is difficult to disentangle the effects of tropical environmental
exposure from the exposures that tend to occur in
low socioeconomic situations. When differences are noted
between febrile seizures in the tropics vs. those in
developed, nontropical regions, we cannot definitively say whether
such differences are due to the tropical environment, socioeconomic
disparities or methodologic study differences.
The ideal epidemiologic study of febrile seizures in the tropics
would be population-based and prospective. The seizure semiology
would be well described, the actual temperature at the time of the
seizure would be documented and a thorough assessment of fever
etiology would be undertaken to understand whether fever etiology
impacts outcome and assure that no primary CNS infection was the
actual cause of the fit. The entire population would be followed
for a sufficient period of time to assess the risk of future
seizures (febrile or unprovoked) and epilepsy as well as other
long-term neurologic outcomes. Such studies are not available and
the interpretation of existing data should be undertaken with the
limitations of each study in mind.
Table 1 Limitations of extrapolating clinical and
epidemiologic findings from US and UK febrile seizure studies to
tropical settings
|
• Children in tropical settings have different underlying
etiologies for fever.
|
|
• Lower threshold/capacity for early care-seeking may impact
duration of fever and/or seizure.
|
|
• A higher frequency of childhood febrile events in tropical
settings — children residing in the tropics may have more
potential exposure to circumstances that predispose to febrile
seizures.
|
|
• The underlying genetic predisposition to febrile seizures may
vary within ethnic or racial subpopulations.
|
|
• The prevalence of underlying brain injury or CNS abnormality may
be higher in the tropics, impacting the number of children eligible
to have febrile seizure (i.e. impacting the denominator).
|
Febrile Seizure Epidemiology
In tropical settings, febrile seizures are one of the commonest
causes of pediatric seizures and a frequent reason for pediatric
hospital admission. Caution is warranted in interpreting the
epidemiologic literature on febrile seizures however, as a
misunderstanding of what is meant by “febrile seizures” is common
and may result in erroneous findings. For example, a 1995 study by
Senenayake (Senanayake and Peiris, 1995) using death certificate
data found that seizure-related deaths among the pediatric
population were commonly attributed to “febrile convulsion”,
strongly suggesting that many healthcare workers filling out such
forms use the term inappropriately. Data derived from hospital
discharge data might be expected to suffer from similar miscoding.
In general, the lifetime risk (LTR) for febrile seizures in the
tropics appears to be higher than the 2-4% seen in developed,
non-tropical regions. A cross-national study conducted in
Pakistan, Bangladesh and Jamaica using a standardized assessment to
capture neurodisability found that febrile seizures were the most
common of neurodisabilities, with an LTR of 10.9-68.2/1.000 (Durkin
et al., 1992). In a birth cohort study among the Chamorro
people of Guam, febrile seizures occurred in 94/1.000 (Stanhope
et al., 1972). This figure was derived from the birth cohort,
and comparative rates obtained from surveys of healthcare workers
in the same regions had a much lower detection rate, illustrating
that results can vary widely based upon the methods of case
ascertainment. In Turkey, the LTR is 9.7% (Aydin et al.,
2008). In southern India the LTR was 10.1%, but these febrile
seizures were associated with a history of perinatal injury and may
have included children with previously unrecognized brain injury
and provoked seizures rather than a febrile seizure (Hackett
et al., 1997). A population-based study in Nigeria
including both urban and rural locations found that among 2.135
children, 172 experienced febrile seizures (8%) (Iloeje, 1991).
Most of the febrile seizures occurred in children between 6 and
12 months of age, a somewhat younger age than at which febrile
seizures are typically thought to occur, but not inconsistent with
findings from other tropical regions. A 3-year,
population-based study of 17.044 children in Tokyo, Japan, found
that febrile seizures occur in 8.3% of children at risk (9.0% in
males and 7.5% in females). In nearby Miyake Island a similar
overall prevalence of 9.9% was reported (Tsuboi, 1984).
A population-based study of 14.010 Parsi children in Mumbai,
India, found that 17.7/1,000 children at risk had experienced
febrile seizures — but information was gathered historically
for children as old as 14-years of age, which might have resulted
in significant undercounting (Bharucha et al., 1991).
Febrile seizures are even more dominant in hospital-based
studies. In Zambia, they account for ~27% of all neurologic
admissions (Birbeck, 2000). In Turkey, febrile seizures accounted
for 46.8% (73/156) of all pediatric seizures seen on the inpatient
service (Cetinkaya et al., 2008). In Kinshasa's tertiary
neuropsychiatric unit, over a 21-month period, febrile seizures
accounted for almost a quarter of all admissions (Ntihinyurwa
et al., 1979). In New Delhi, febrile seizures comprised 28% of
all pediatric admissions at a tertiary care center (Sehgal and
Bala, 1979).
Fever Etiology
The etiology of febrile seizures in a population will generally
follow the epidemiology of pediatric fevers within that population.
However, some infections specific to the tropics may be more likely
to cause febrile seizures. Within malaria-endemic regions, most
previous studies have determined that malaria is the most common
infection associated with febrile seizures (Chomba et al.,
2008; Iloeje, 1991). However, past studies of malaria may have
misattributed fevers to malaria in regions where asymptomatic
parasitemia is common in pediatric populations and the local
languages use the same words for “malaria” and “fever”.
Novel infections may warrant consideration if high rates
of febrile seizures are being seen. In Hong Kong, a novel
coronavirus (HKU1) has been recently described as the cause of a
community-acquired pneumonia. Although the HKU1 accounted for only
2.1% of all pneumonia infections requiring hospital admission per
nasopharyngeal aspirate, 50% of children admitted with HKU1
pneumonia had febrile seizures. It was noted that these children
had no difference in maximum temperature relative to that induced
by other common viruses such as adenovirus, parainfluenza and RSV,
which had a febrile seizure incidence of 0-14%. Whether HKU1 has
any particular neurotropism is unknown.
The emerging arbovirus infection, Chikungunya, has been reported
in a retrospective chart review of 30 cases from La Réunion to
be associated with a 33% incidence of febrile seizures (Robin
et al., 2008). Notably, 12/30 cases had a clinical
encephalopathy not consistent with febrile seizure, and the
possibility of an arbovirus causing encephalitis must be considered
a potential underlying cause for the fits rather than febrile
seizure. Similarly, reports of dengue causing seizures in children
must be cautious about labeling these events as “febrile seizures”
(Pancharoen and Thisyakorn, 2001). The age range affected has been
reported to include as old an age as 13 years, well outside
the range of age-dependent susceptibility. There is also an
associated encephalopathy in some children with dengue.
Consideration of other metabolic causes of seizure should be
considered (e.g. hyponatremia). In such cases, the diagnosis of
febrile seizure must be one of exclusion.
In many regions, febrile seizures are known to have a seasonal
predisposition. In regions where malaria is endemic with a seasonal
prevalence, children invariably suffer from more fevers during the
malaria season (Chomba et al., 2008). In Singapore seasonality
to febrile seizures has been reported, which appears to positively
correlate with admissions for pharyngitis, chest infections and
gastroenteritis, leading the authors to conclude that these
represent seasonal viral infections (Tay et al., 1983). In
Hong Kong, the prevalence of febrile seizures among 923 consecutive
admissions for the 5 most common viruses was reviewed and some
differences were evident in terms of febrile seizure
prevalence—influenza 20.8%; parainfluenza 20.6%; adenovirus 18.4%,
RSV 5.3% and rotavirus 4.3% (Chung and Wong, 2007). While some have
suggested that viruses known to have neurotrophic properties like
human herpesvirus 6 (HHV6) may be more likely to produce febrile
seizures, formal studies have not definitely supported this
hypothesis (Hukin et al., 1998; Pancharoen et al.,
2000).
The Risk of Febrile Seizures
Studies in the tropics have uniformly indicated that male children
are more likely to have febrile seizures than female children, with
ratios as high as 2:1 reported (Izuora and Azubuike,1977; Iloeje,
1991; Bharucha et al. 1991; Sehgal and Bala, 1979). This may
represent a biological vulnerability, but the possibility of
gender-related care-seeking bias as a contributing factor must also
be considered. Some reports have indicated that well-nourished
children are more predisposed to febrile seizures than children who
are marginalized nutritionally. Well-nourished children do not
appear to be at higher risk of complex febrile seizures though
(Oseni et al., 2002). Most epidemiologic studies of febrile
seizures in the tropics have confirmed that, as in developed
regions, genetic vulnerability plays a role. A family history
of febrile seizures is consistently found to be a risk factor for
tropical febrile seizures (Chomba et al., 2008, Iloeje, 1991;
Gururaj et al., 2001). Consanguinity may play a role in this
genetic predisposition in some regions (Iloeje, 1991). Duration and
height of fever may also be important (Chomba et al., 2008,
Gururaj et al., 2001).
Complex febrile seizures are more common and more complex in
tropical regions, and within tropical regions, they may be more
common in rural areas (Chomba et al., 2008; Iloeje, 1991).
This may reflect inevitable delays in accessing care from rural
locations, but could be related to different fever etiologies
— for example in many regions, malaria is primarily a rural
disease. In developed country reports, children with complex
febrile seizures usually have only one of the three features of a
complex febrile seizure — prolonged or recurrent or focal. In
contrast, in a tropical setting, children with complex febriles
seizures often have more than one complex feature (Chomba
et al., 2008; Oseni et al., 2002; Canagarayar and Soysa,
1987; Ling, 2001). A study in Zambia found that 68.2% of
children who presented for care with febrile seizures had complex
febrile seizures, with over half of these children having more than
one complex feature (Chomba et al., 2008).
Risk of Recurrent Seizures and/or Epilepsy
Studies from the US and UK are reassuring in that children who
experience simple febrile seizures have only a marginal increase in
the risk of developing epilepsy. The detailed findings of these
studies may be less reassuring in that the children with complex
febrile seizures had a substantially high rate of unprovoked
seizures and epilepsy.
Established risk factors for recurrent febrile seizures in the
US and the UK include a family history of febrile seizures, a
history of prior febrile seizures, a younger age at the time the
febrile seizure occurred (probably because it signifies that the
child has more years left at a susceptible age) (Berg et al.,
1998; Berg et al., 1991).
The risk of epilepsy development after febrile seizure,
particularly complicated febrile seizures in the tropics, exceeds
rates reported from developed regions. For example in a prospective
study in rural Zambia, 11% of children who presented with febrile
seizures developed epilepsy over a 36 months observational
study (Chomba et al., 2008). In Nigeria, using retrospective
methods, it was determined that epilepsy had developed in 15-21% of
children with febrile seizures (Izuora et al., 1977). Both of
these reports included mainly children who had complex febrile
seizures, and children who experience focal febrile seizures appear
to be particularly at risk for later epilepsy, with rates as high
as 41%. Retrospective studies of epilepsy in Kenya also found
febrile seizures to be a risk factor for epilepsy (Mung'ala-Odera
et al., 2008). Whether the development of epilepsy is a marker
of acute injury at the time of the febrile seizure or reflects
an underlying brain injury or predisposition to seizures (i.e.
whether seizures beget seizures) remains unclear.
Assessments to determine if a family history of febrile seizures
is a risk factor for febrile seizures in the tropics
are notable for the very high rate of children who have a
relative with a febrile seizure history relative to reports from
nontropical regions. For example, in Nigeria, 69% of children with
febrile seizures reported a positive family history for any
relative, 55% for a primary relative (Obi et al., 1994).
Larger family size affects these figures but not likely enough to
explain the differences with the US rate of 7.3% (Nelson and
Ellenberg, 1978)
A higher rate of complex febrile seizures
Studies from tropical settings uniformly indicate that a higher
proportion of children experience complex febrile seizures rather
than simple febrile seizures relative to non-tropical, developed
settings. Potential reasons for this difference include: (1) a
selection bias for more severely ill children in tropical settings
where barriers to accessing care are more substantial; (2) a higher
rate of pre-existing brain injury resulting in prolonged or focal
seizures in the setting of a provoked seizure; (3) delays in care
delivery resulting in delayed treatment of fever and seizure after
an initial simple febrile seizure; (4) different fever etiologies
with some in tropical infections being more likely to cause
complicated febrile seizure.
A retrospective chart review of 448 children with febrile
seizures seen in Malaysia found that multiple seizures were much
more common than in studies from the West and transient neurologic
abnormalities were consistent with a Todd's paralysis were common
(Ling, 2000). In a retrospective chart review from Malaysia, among
379 children seen with their first febrile seizure over a 2-year
period, 37.2% had complex febrile seizure, with many being both
prolonged and focal (Ling, 2001). In this study, risk factors for
complex febrile seizures included age <15 months,
birth weight <2 kg and temperature <38°°C.
Neurologic exam findings were more likely to be abnormal in
children who had two or more complex features to their febrile
seizure. This was also found to be true among Zambian children
presenting with their first febrile seizure (Chomba et al.,
2008).
Clinical Management
For children with simple febrile seizures who present after their
seizure, often fully recovered and awake, acute management requires
those measures usually undertaken to evaluate and manage any
febrile child. Namely, (1) assure the child is otherwise stable,
(2) identify the cause of the fever, if possible, and initiate
treatment, if indicated. Additional efforts are warranted to assure
one that the seizure is not a symptomatic seizure related to an
underlying CNS infection, and relatively aggressive measures for
fever control should be undertaken. Fever management should avoid
the use of aspirin, given the risk of Reyes’ syndrome. Either
acetaminophen or ibuprofen or both, if necessary for maintaining
normothermia, may be used. External cooling in the form of cold
baths should be avoided since these measures may precipitate
shivering, which can actually increase rather than decrease the
child's core temperature. Tepid sponging with fan cooling in
tropical climates is ideal. Mothers who may otherwise have a
tendency to over-bundle their children in multiple layers of thick
clothing should be educated about the need to allow them to remain
as cool as possible when febrile.
In children who present with complex febrile seizures, acute
management may also require an intervention to stop the seizure
itself. For recurrent or prolonged febrile seizures,
benzodiazepines are the first-line treatment of choice. Lorazepam
is preferred over diazepam, but otherwise, rapid administration of
whatever parental benzodiazepine is available should be undertaken.
Diazepam should not be given intramuscularly however, as
distribution is unpredictable and precipitation of the drug within
the muscle is a risk. For the rare case of febrile status
epilepticus, phenytoin or phenobarbitone may be required. Caution
in the administration of these agents in settings without recourse
to mechanical ventilation is critical. Children who have already
received benzodiazepines may be more susceptible to the respiratory
suppression effects of these agents (Crawley et al., 2000).
Where newer antiepileptic agents such as intravenous levetiracetam
or valproic acid are available, these can be considered. There is a
growing body of evidence suggesting the safety and efficacy of
these agents in pediatric status. Unfortunately, resource-poor
settings without easy access to mechanical ventilation and
intensive care are unlikely to have these newer, more expensive
AEDs available.
Complex febrile seizures require close evaluation to assure that
an underlying CNS infection is not present. Much debate has
occurred regarding the pros and cons of routinely obtaining
cerebrospinal fluid from children with febrile seizures (Akpede
et al., 1992; Owusu-Ofori et al., 2004; Vince, 1992;
Donaldson et al., 2008; Deng et al., 1994; Sowunmi,
1997). Practicalities related to laboratory capacity may need to be
considered in some resource-limited settings. Ultimately, when
performed appropriately the lumbar puncture is a safe, minimally
invasive procedure. Where formal studies have been undertaken,
findings consistently indicate that seizures related to CNS
infections are clinically misdiagnosed as febrile seizures
frequently enough to encourage the cautious clinician to be
inclined to obtain CSF remembering that is only abnormal CSF is
obtained, one has likely missed some infections (Ramadas
et al., 1990). Studies in Ghana found that among
186 children initially labeled as “febrile seizure”, 102% (19)
were actually found by lumbar puncture to have bacterial
meningitis, with a >36% case fatality rate. In addition, 20% of
children with a confirmed bacterial meningitis had a peripheral
blood smear with p. falciparum present, reiterating the reality
that malaria parasites may be present and incidental infection or
coinfection and identification of malaria parasites in a febrile,
convulsing child does not definitely rule out the possibility of
meningitis. Recent identification of a malaria-specific retinopathy
may help determine whether a child with fits and/or coma has true
cerebral malaria vs. an incidental parasitemia and another cause
for the underlying seizures (Beare et al., 2009; Beare
et al., 2006).
For children with complex febrile seizures, a close evaluation
to determine if the child has developmental delays or pre-existing
neurodisability is also warranted. The presence of either increases
the child's risk of future, unprovoked seizures. Antiepileptic
drugs (AEDs) may not be necessary, but in regions where untreated
epilepsy is the norm, intermittent follow-up of these children to
facilitate the early diagnosis and treatment of epilepsy if/when it
develops may decrease the incidence of seizure-related morbidity
and mortality (Birbeck, 2000).
The use of chronic AEDs is generally not indicated for febrile
seizure management. Treatment may inhibit seizures transiently, but
has not been shown to affect the long-term risk of seizures and the
chronic use of standard AEDs (phenytoin, phenobarbitone, valproic
acid) is associated with cognitive impairment when given
prophylactically. Exceptional circumstances may lead one to
initiate AEDs after a febrile seizure — for example, a child
with febrile status epilepticus who resides in a region with very
limited medical access. Where recurrent, prolonged febrile seizures
occur seasonally due to malaria, intermittent preventive treatment
with an antimalarial could be considered instead of an AED until
the child is old enough to no longer be predisposed to febrile
seizures or severe malaria.
The acute management of febrile seizures must also include
proactive education of the parents about the likelihood of future
seizures, first-aid management of a febrile seizure and appropriate
fever management. First-aid management needs to be accompanied by
explicit information on what NOT to do — no administration of
oral bush teas or home remedies, and especially while the child is
unconscious, do not place anything in the child's mouth, etc.
Familiarity with local traditional medicine practices may allow the
physician to be very explicit with parents regarding activities to
be avoided.
The administration of traditional medicines to children with
febrile seizures can result in major oral injuries, oral and facial
burns, aspiration pneumonia and death (Canagarayar and Soysa, 1987
; Birbeck, 1999). Up to a third of children presenting for care at
a Nigerian teaching hospital were noted to have such injuries and
admitting clinicians may need additional education to be aware of
these risks so they assess for such injuries (Ndukwe et al.,
2007). The administration of enemas, blowing smoke into the anus or
nostrils, and even placing a child's feet in fire to “chase the
evil away” are all reported means of traditional healers’
management of febrile seizures (Voorhoeve, 1980). The nature of
these interventions is a testimony to the parent's underlying
anxiety — primarily that the febrile seizure is a harbinger of
epilepsy, which is so heavily stigmatized in many regions (Parmar
et al., 2001). For those children with simple febrile seizures
and normal developmental status, reassuring the parents that the
child is most likely going to outgrow these events is an important
educational aspect to consider (Kurugol et al., 1995).
Conflicts of interest
none.
References
[Akpede et al., 1992] Akpede GO, Sykes RM,
Abiodun PO. Indications for lumbar puncture in children
presenting with convulsions and fever of acute onset: experience in
the Children's Emergency Room of the University of Benin Teaching
Hospital, Nigeria. Ann Trop Paediatr 1992; 12: 385-9.
[Aydin et al., 2008] Aydin A, Ergor A,
Ozkan H. Effects of sociodemographic factors on febrile
convulsion prevalence. Pediatr Int 2008; 50: 216-20.
[Beare et al., 2009] Beare NA, Glover SJ,
Molyneux M. Malarial retinopathy in cerebral malaria. Am J
Trop Med Hyg 2009; 80: 171.
[Beare et al., 2006] Beare NA, Taylor TE,
Harding SP, Lewallen S, Molyneux ME. Malarial
retinopathy: a newly established diagnostic sign in severe malaria.
Am J Trop Med Hyg 2006; 75: 790-7.
[Berg et al., 1998] Berg AT, Darefsky AS,
Holford TR, Shinnar S. Seizures with fever after
unprovoked seizures: an analysis in children followed from the time
of a first febrile seizure. Epilepsia 1998; 39: 77-80.
[Berg and Shinnar, 1991] Berg AT, Shinnar S. The risk
of seizure recurrence following a first unprovoked seizure: a
quantitative review. Neurology 1991; 41: 965-72.
[Bharucha et al., 1991] Bharucha NE, Bharucha EP,
Bharucha AE. Febrile seizures. Neuroepidemiology 1991; 10:
138-42.
[Birbeck, 1999] Birbeck GL. Traditional African medicines
complicate the management of febrile seizures. Eur Neurol 1999; 42:
184.
[Birbeck, 2000] Birbeck GL. Seizures in rural Zambia.
Epilepsia 2000; 41: 277-81.
[Canagarayar and Soysa, 1987] Canagarayar UT, Soysa P.
Management of febrile seizures in a developing country. J Trop Med
Hyg 1987; 90: 161-4.
[Cetinkaya et al., 2008] Cetinkaya F,
Sennaroglu E, Comu S. Etiologies of seizures in young
children admitted to an inner city hospital in a developing
country. Pediatr Emerg Care 2008; 24: 761-3.
[Chomba et al., 2008] Chomba E, Taylor T,
Hauser W, Wasterlain C, Organek N, Birbeck G.
Seizure recurrence in rural Zambian children admitted with febrile
seizures. Open Trop Med J 2008; 1: 101-7.
[Chung and Wong, 2007] Chung B, Wong V. Relationship
between five common viruses and febrile seizure in children. Arch
Dis Child 2007; 92: 589-93.
[Crawley et al., 2000] Crawley J, Waruiru C,
Mithwani S, et al. Effect of phenobarbital on seizure
frequency and mortality in childhood cerebral malaria: a
randomised, controlled intervention study. Lancet 2000; 355:
701-6.
[Deng et al., 1994] Deng CT, Zulkifli HI,
Azizi BH. Parents' views of lumbar puncture in children with
febrile seizures. Med J Malaysia 1994; 49: 263-8.
[Donaldson et al., 2008] Donaldson D, Trotman H,
Barton M, Melbourne-Chambers R. Routine laboratory
investigations in infants and children presenting with fever and
seizures at the University Hospital of the West Indies. West Indian
Med J 2008; 57: 369-72.
[Durkin et al., 1992] Durkin MS, Davidson LL,
Hasan ZM, et al. Estimates of the prevalence of childhood
seizure disorders in communities where professional resources are
scarce: results from Bangladesh, Jamaica and Pakistan. Paediatr
Perinat Epidemiol 1992; 6: 166-80.
[Fukuda et al., 1997] Fukuda M, Morimoto T,
Nagao H, Kida K. The effect of GABAergic system activity
on hyperthermia-induced seizures in rats. Brain Res Dev Brain Res
1997; 104: 197-9.
[Ganesh and Janakiraman, 2008] Ganesh R,
Janakiraman L. Serum zinc levels in children with simple
febrile seizure. Clin Pediatr (Phila) 2008; 47: 164-6.
[Gururaj et al., 2001] Gururaj A, Bener A,
Al-Sweidi E, Al-Tatari H, Khadar A. Predictors of
febrile seizures: a matched case-control study. J Trop Peds 2001;
47: 361-2.
[Hackett et al., 1997] Hackett R, Hackett L,
Bhakta P. Febrile seizures in a south Indian district:
incidence and associations. Dev Med Child Neurol 1997; 39:
380-4.
[Hukin et al., 1998] Hukin J, Farrell K,
MacWilliam LM, et al. Case-control study of primary human
herpesvirus 6 infection in children with febrile seizures.
Pediatrics 1998; 101: E3.
[Iloeje, 1991] Iloeje SO. Febrile convulsions in a rural
and an urban population. East Afr Med J 1991; 68: 43-51.
[Izuora and Azubuike, 1977] Izuora GI, Azubuike JC.
Prevalence of seizure disorders in Nigerian children around Enugu
(a preliminary report). Cent Afr J Med 1977; 23: 80-3.
[Kurugol et al., 1995] Kurugol NZ, Tutuncuoglu S,
Tekgul H. The family attitudes towards febrile convulsions.
Indian J Pediatr 1995; 62: 69-75.
[Ling, 2001] Ling SG. Clinical characteristics and risk
factors for a complex first febrile convulsion. Singapore Med J
2001; 42: 264-7.
[Ling, 2000] Ling SG. Febrile convulsions: acute seizure
characteristics and anti-convulsant therapy. Ann Trop Paediatr
2000; 20: 227-30.
[Mung'ala-Odera et al., 2008] Mung'ala-Odera V,
White S, Meehan R, et al. Prevalence, incidence and
risk factors of epilepsy in older children in rural Kenya. Seizure
2008; 17: 396-404.
[Ndukwe et al., 2007] Ndukwe KC, Folayan MO,
Ugboko VI, Elusiyan JB, Laja OO. Orofacial injuries
associated with prehospital management of febrile convulsion in
Nigerian children. Dent Traumatol 2007; 23: 72-5.
[Nelson and Ellenberg, 1978] Nelson KB, Ellenberg JH.
Prognosis in children with febrile seizures. Pediatrics 1978; 61:
720-7.
[Ntihinyurwa et al., 1979] Ntihinyurwa M,
Omanga U, Dechef G, Shako D. Epidemiology of
infantile convulsions in Kinshasa, Zaire. Ann Soc Belg Med Trop
1979; 59: 309-23.
[Obi et al., 1994] Obi JO, Ejeheri NA,
Alakija W. Childhood febrile seizures (Benin City experience).
Ann Trop Paediatr 1994; 14: 211-4.
[Oseni et al., 2002] Oseni SB, Esimai VC,
Oyedeji GA, Adelekan DA. Indices of nutritional status in
children with febrile convulsion. Nutr Health 2002; 16: 143-4.
[Owusu-Ofori et al., 2004] Owusu-Ofori A,
Agbenyega T, Ansong D, Scheld WM. Routine lumbar
puncture in children with febrile seizures in Ghana: should it
continue? Int J Infect Dis 2004; 8: 353-61.
[Pancharoen and Thisyakorn, 2001] Pancharoen C,
Thisyakorn U. Neurological manifestations in dengue patients.
Southeast Asian J Trop Med Public Health 2001; 32: 341-5.
[Pancharoen et al., 2000] Pancharoen C,
Chansongsakul T, Bhattarakosol P. Causes of fever in
children with first febrile seizures: how common are human
herpesvirus 6 and dengue virus infections? Southeast Asian J Trop
Med Public Health 2000; 31: 521-3.
[Parmar et al., 2001] Parmar RC, Sahu DR,
Bavdekar SB. Knowledge, attitude and practices of parents of
children with febrile convulsion. J Postgrad Med 2001; 47:
19-23.
[Ramadas et al., 1990] Ramadas D, Pasupati J,
Kugathasan S. Seizures associated with fever in children. J
Trop Pediatr 1990; 36: 46.
[Robin et al., 2008] Robin S, Ramful D, Le
Seach F, Jaffar-Bandjee MC, Rigou G,
Alessandri JL. Neurologic manifestations of pediatric
chikungunya infection. J Child Neurol 2008; 23: 1028-35.
[Sehgal and Bala, 1979] Sehgal H, Bala K. Febrile
convulsions in children. (A clinical profile of 150 cases). Indian
Pediatr 1979; 16: 479-82.
[Senanayake and Peiris, 1995] Senanayake N, Peiris H.
Mortality related to convulsive disorders in a developing country
in Asia: trends over 20 years. Seizure 1995; 4: 273-7.
[Sowunmi, 1997] Sowunmi A. Clinical study of cerebral
malaria in African children. Afr J Med Med Sci 1997; 26: 9-11.
[Sperber et al., 1999] Sperber EF, Veliskova J,
Germano IM, Friedman LK, Moshe SL. Age-dependent
vulnerability to seizures. Adv Neurol 1999; 79: 161-9.
[Stanhope et al., 1972] Stanhope JM, Brody JA,
Brink E, Morris CE. Convulsions among the Chamorro people
of Guam, Mariana islands. II. Febrile convulsions. Am J Epidemiol
1972; 95: 299-304.
[Tay et al., 1983] Tay JS, Yip WC, Yap HK.
Seasonal variations in admissions to a tropical paediatric unit.
Trop Geogr Med 1983; 35: 167-72.
[Tsuboi, 1984] Tsuboi T. Epidemiology of febrile and
afebrile convulsions in children in Japan. Neurology 1984; 34:
175-81.
[Vince, 1992] Vince JD. Convulsions in children. P N G Med
J 1992; 35: 144-51.
[Voorhoeve, 1980] Voorhoeve HM. Childhood convulsions in
the tropics. Trop Doct 1980; 10: 122-3.
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