Developing Countries Perspective

Jing-Jane Tsai Introduction

Febrile seizure is the most common seizure disorder in childhood. Often the terms "febrile convulsion" and "febrile seizure" are used synonymously or interchangeably. In the newly proposed classification this seizure disorder has been recognized as a special syndrome and the term "febrile seizures" (FS) has been proposed.1,2 Epidemiological studies of FS are very few from the developing countries and show some differences not only in the incidence and prevalence rates but also in the clinical features, etiology, management, and outcome when compared to developed countries.

Epidemiology

Epidemiological studies from developing countries are mostly prevalence studies and the reported prevalence varied between 1.33% and 11. 61% (Table 1),3-9 whereas the reported prevalence rates from developed countries was between 2% and 5%.10-12 The lowest prevalence rate was reported from Saudi Arabia.13 However, studies from some Asian countries7 reported prevalence rates similar to those reported from developed countries. The wide range in the prevalence reported from the developing countries is probably related to the methodological issues.14 The reported higher rates from the non-Occidental countries are attributed to high incidence of childhood infections and environmental factors and also probably to genetic factors.

Clinical Manifestations

The core entity of the clinical features of FS includes the relevant issues in the child, the illness and the seizures. Various definitions of FS have been developed for the convenience of clinical study,10-15 thus the natural history of FS is artificially and unavoidably distorted. FS are classified as simple (typical) and complex (complicated or atypical) FS without uniform definition. Simple FS is usually a brief generalized tonic-clonic seizure and occurs only once in 24 hours during fever, whereas complex FS have focal onset, longer (> 15 minutes) seizure duration, or more than one seizure during 24 hours.16 A higher frequency of complex FS, 13.6%9 and 30%17 have been reported from the developing countries, whereas in a more recent population-based study from a developed country, complex FS was the initial FS type in only 8.6% of the patients.18 The possible explanations for the differences include time delay in seeking medical attention, less frequent use of diazepam, ineffective routes for administering diazepam, and probably the cause of the febrile episode.17

Table 1. Selected recent reports of the prevalence of febrile seizure in some developing countries

Prevalence Community/ Number with FS/

Author, Year Rate (%) Country Subject Number Surveyed

Bharucha et al,

1.77

Parsis/India

<14 yrs

28/1581

19913

Iloeje, 19914

11.61

Amokwe/Nigeria

6 mos-6 yrs

72/620

8.05

Enugu/Nigeria

172/2135

Aziz, et al,

1.33

Sind/Pakistan

All age

322/24130

19945

Okan, et al,

4.48

Gemlik/Turkey

5 yrs

224/5002

19956

Tsai, et al,

3.2

Taiwan

6 mos-6 yrs

111/3462

19967

Hackett et al,

10.1*

Kerala/India

8-12yrs

120/1192

19978

Yakinci et al,

3.24

Malatya/Turkey

7-12 yrs

118/3637

20009

Predisposing Factors

Family history of FS is the most consistent and significant predisposing factor.19,20 History of FS in a first-degree or a higher degree relative was found in most studies.10,21,22 Familial aggregation of FS is more evident in the siblings than in the parents.21-23 Several prenatal and perinatal factors have been described as predisposing risk factors for FS.19,21 However, their role seems to be minor. Some of the perinatal risk factors like low birth weight, breech delivery, neonatal discharge time of at least 28 days, neonatal sepsis, difficult birth, and neonatal asphyxia are more likely to be associated with the poor socioeconomic state.19 Some of the described predisposing risk factors may have a potential negative effect on the developing brain. Neurological abnormalities, including developmental delay also predispose to FS.19 Recently an association between iron-deficiency anemia, a common disorder of children in the developing countries, and FS has been reported.24 Most of the risk factors described are more frequent in the developing countries and may be improved by the integrated maternal, obstetric and perinatal care.

Precipitating Factors

The significant precipitating risk factors for FS include the degree of fever20 and the frequency of febrile illnesses.21 The most commonly reported febrile illnesses are upper respiratory tract infections and otitis media.10 Children with primary infection with human herpes virus-6 (HHV6) often develop FS.2 The pattern of the underlying febrile illness is similar in both developed and developing countries.10,26 However, certain infections like exanthematous fevers and malaria are still endemic in the developing countries. In Central Africa, malaria accounts for five per cent of pediatric emergencies.27,28 Vivax malaria is a frequent cause of typical FS in the endemic regions and FS can be the presenting feature of Falciparum malaria.14,27

FS following immunization is well known. The significance of immunization as a risk factor for FS has been the focus of debate. However meta-analysis of the data suggests diphtheria-tetanus-pertussis (DTP) vaccination is associated with a relative risk of FS.29 FS following immunization has the highest incidence at the age when children are most susceptible to seizures from febrile illnesses of any cause.30 The risk to develop FS is high in children with a family history of seizures.31 Though there is a small risk of FS following immunization, the benefits of vaccination with DTP and MMR vaccines should not be deprived to children in the regions endemic to these diseases.

Diagnostic Evaluation

The diagnostic criterion for FS is, seizures in children in association with fever and absence of central nervous system infections. However, acute symptomatic seizures associated with acute febrile medical or neurological disease may pose difficulties in the diagnosis. Detailed analysis of the history, fever characteristics, physical and neurologic examination findings may differentiate the two conditions. In children with fever and acute seizures, age less than 6 month, complex FS, unarousable coma, or presence of extracranial focus of infection should warrant exclusion of CNS infection, more so in developing countries.32

In developing countries lumbar puncture is frequently performed in children in the presence of fever and seizures to rule out CNS infections. The yield for bacterial meningitis is less than 5%.32,33 However, lumbar puncture is indicated in certain clinical circumstances, which include signs of meningism or clinical suspicion of meningitis, complex FS, prolonged sensorial alterations, and age less than 18 months, more so if the age is less than 12 months.34 Clinical signs of meningitis may not be present in about 25% of the children.

Knowledge, Attitude and Practice

Ongoing seizure is a frightening scene for the parents. The parents will also be anxious about the affect of seizure on the brain and cognitive development. Their concerns also include chance of recurrence and subsequent epilepsy. The reasons for these concerns among the parents include lack of knowledge about FS, high concerns, and improper first-aid practices.35 Studies from the developing countries have shown that at times some of the parents felt as if the child is dying or dead during the attack.37,38 Active educational intervention has been found to have a positive effect on the parental concerns.35,38,39 Parents need to be educated about the benign nature of FS, recognition and management of fever, use of antipyretic medication, home management of seizures, and timing of bringing the child to the hospital.

Pharmacotherapy

Drug treatment of FS, especially simple FS, has long been a controversial issue. Recently consensus recommendations have been evolved.40,41 However, these recommendations are not absolute but only guide the practicing physicians to treat the child with FS.

Antipyretics are used to control the temperature and thus to prevent seizure recurrence. Although antipyretics may also improve the comfort of the child, vigorous reduction of fever does not influence the chance of seizure recurrence.42

Prophylactic use of anticonvulsants to prevent recurrence of FS is unclear. Prophylactic treatment with phenobarbitone43 or valproic acid44 and intermittent therapy

with diazepam45,46 are effective in reducing the risk of recurrence. However, the efficacy of phenobarbitone and sodium valproate in preventing recurrence is found to be uncertain when trials are analyzed on an intention to treat basis.47,48 Furthermore, compliance is usually poor and the potential side effects outweigh the relatively minor risks associated with simple FS in the long-term prophylactic therapy.15 Prophylactic therapy does not influence the later development of epilepsy.49 Thus the general consensus is against prophylactic anticonvulsant therapy.50 Situations whence most authorities would consider prophylaxis are among children with complex FS, children in isolated remote areas, or very high parental anxiety despite appropriate counselling and reassurance.51-53 If the parental anxiety is severe, intermittent oral diazepam at the onset of febrile illness may be advised.

Prognosis

FS are benign with excellent prognosis.54-56 Short-term morbidity and mortality of febrile status epilepticus is low57 and the mortality of febrile status epilepticus is primarily related to the underlying cause.58

Recurrence of Febrile Seizures

About one-third of children with FS experience one or more recur-

rences.10,11,15,16,59-62 A higher recurrence rate (66%) has been described in some studies from developing countries.63,64 Independent risk factors predicting likelihood of recurrence are young age at time of first FS (< 18 months), history of FS in a first-degree relative, low degree of fever while in the emergency department, brief duration between onset of fever and the FS.15,59-62,65 Risk of recurrence is significantly high if the child has more than one risk factor.61,65 In a study in south India perinatal adversity has been found to be associated with recurrence of FS.64 These observations suggest chance of recurrence of FS is a complex interaction between genetic and environmental factors.50

Risk of Epilepsy

In the population-based studies the reported chance of developing epilepsy following FS varied between 2 to 6%.16,66-68 Children who have a single, brief generalized seizure (simple FS), a negative family history of epilepsy, and no preexisting neurologic handicap have no or minimal increased risk of developing epilepsy. The risk factors associated with developing epilepsy include seizure duration greater than 15 minutes, focal seizures, abnormal preexisting neurologic deficit, seizure recurrence in the first 24 hours, and history of epilepsy in a parent or sibling.12,16,68 However, the risk of occurrence of late epilepsy in children with febrile status epilepticus is different. In the British study of the 19 children with febrile status epilepticus, four (21%) developed subsequent afebrile seizures and two of them developed epi-

lepsy.69

The type of epilepsy that develops after FS can be generalized or partial epilepsy. The association between mesial temporal scleroses with intractable complex partial seizure is well documented. However, the cause-effect relationship between the two is still unsolved.70

Behavior and Cognition Outcome

The behavior and cognition outcome of FS is a subject of controversy for a long time. Earlier hospital-based studies observed a relatively high incidence of mental retardation, behavioral disturbances, and academic difficulties in children with a history of FS.71,72 Adverse outcome on intelligence has been

observed in children with prolonged FS.73 However, these observations have not been substantiated in population-based studies.56,64,74-77 Furthermore, children with FS have been shown to have significantly better mnemonic capacity, more flexible mental processing and higher impulsivity, better control of distractibility, and attention.76,77 Onset of—FS before one year of age has been found to be associated with compromised mnemonic function and prior neurodevelopmental delay was associated with defects in executive function.76,77

Conclusions

Inadequate knowledge, improper attitude and practice dealing with FS still prevail in every corner of the world. These greatly hamper the quality care of FS. The strategy of planning educational intervention becomes an important issue for modern care of FS. Medical personnel in tropical countries can take advantage of the experiences from developed countries for daily practice of the diagnosis and management of FS in general which should be adjusted with special consideration of local/regional specific problems. The researches specifically designed for the investigation of the significantly controversial issues can be conducted in tropical countries and may contribute to the comprehensive understanding of FS.

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