Description of the condition
According to the National Institutes of Health (NIH) and the International League Against Epilepsy (ILAE), febrile seizures can occur between the ages of one month and five years (Freeman 1980; ILAE 1993) and are associated with fever with no intracranial infection or defined cause (Freeman 1980). Febrile seizures can be classified as simple or complex. Simple febrile seizures are generalised tonic or tonic-clonic convulsions lasting less than 15 minutes that occur only once in a 24-hour period in a neurologically and developmentally normal child. If focal features are present, the seizures last longer than 15 minutes, the child has a pre-existing neurological condition and the seizures occur multiple times (recurrent within 24 hours) or within the same febrile event, the febrile seizures are referred to as complex (Francis 2006; Kevin 2001; Kliegman 1996; Waruiru 2004). The incidence of febrile seizures varies from 2% to 5% in Western Europe and the United States (Joshi 2005; Waruiru 2004) and from 5% to 10% in India and is reported at 8.8% in Japan and 14% in Guam (Waruiru 2004). Data from the developing world are limited (Waruiru 2004).
A child with febrile seizures usually does not need to be hospitalised. However, when the seizure is prolonged or is accompanied by a serious infection, or when the source of the infection cannot be determined, hospitalisation for observation may be recommended. Prolonged daily use of oral antiepileptic drugs to prevent febrile seizures usually is not recommended because of their potential for side effects and their questionable effectiveness in preventing such seizures (Kliegman 1996; Offringa 2012)
Description of the intervention
An electroencephalograph (EEG) records brain waves detected by electrodes placed on the scalp. Reporting of paroxysmal EEG abnormalities in children with febrile seizures may vary widely (Panayiotopoulos CP 2005). The reasons may be related to differences in participant selection by different authors, the criteria used in different studies to define paroxysmal discharges or the timing of the EEG.
The American Academy of Pediatrics practice parameter on febrile seizures recommends that an EEG should not be part of a routine investigation after a simple febrile seizure in neurologically normal children because of its lack of usefulness in predicting recurrence risk or future epilepsy (American Academy of Pediatrics 1996; Joshi 2005; Kuturec 1997). The quality standards subcommittees of the American Academy of Neurology, the Child Neurology Society and the American Epilepsy Society recommend an EEG in the initial evaluation of the first afebrile seizure, as an abnormal EEG predicts recurrence (Hirtz 2000; Joshi 2005). The precise role of EEG in the evaluation of patients with complex febrile seizure (CFS) has not been established; however, it is common for both paediatricians and specialists to recommend EEGs on these patients (Joshi 2005; Millichap 1991) in some countries. An EEG taken within the first week after a febrile seizure is termed an 'early EEG', whereas an EEG taken anytime between the first week and one month after the seizure activity is termed a 'late EEG'. Few retrospective studies have tried to assess the use of EEGs in complex febrile seizure (Maytal 2000; Yucel 2004).
How the intervention might work
An EEG performed in the evaluation of complex febrile seizures may help identify the nature of the underlying acute or remote cerebral pathology and predict the risk of future seizures.
Why it is important to do this review
Much uncertainty remains about the use of an EEG and its timing in children with complex febrile seizures, hence it is necessary to carry out this review.
To assess the use of EEG and its timing after complex febrile seizures in children younger than five years of age.
Criteria for considering studies for this review
Types of studies
We planned to include parallel-group randomised controlled trials (RCTs).
Types of participants
Participants in the studies eligible for inclusion were children of either sex younger than five years of age with first episode of complex febrile seizure.
Participants would be included in the review only:
- if the EEG was performed after the first complex febrile seizure episode; or
- if recruitment of participants into the study was delayed and the EEG was performed before the participant's second seizure.
We excluded studies in which participants had other neurological disorders (e.g. behavioral disorders, cerebral palsy, mental retardation).
Types of interventions
The intervention is EEG investigation (i.e. electroencephalography). Two comparisons are made.
- Participants without administration of an EEG versus participants with administration of an EEG (early or late or at any time).
- Participants with administration of an early EEG versus participants with administration of a late EEG.
Types of outcome measures
- Proportions of participants developing seizures of any type after follow-up periods of one month, six months, twelve months and two years in two comparison groups of EEG versus no EEG and early EEG versus late EEG.
We decided to include any type of seizure in the outcome. We recorded the available outcome measures with respect to a particular time period. We planned additionally to contact the original trial authors to enquire whether outcome measurements had been recorded for other time periods of interest. We believe that the most important clinically relevant time period was two years.
- Risk of recurrence between no EEG and EEG (early EEG, late EEG or any other time), which will act as a surrogate outcome.
- Total number of seizure episodes in each group during the two-year follow-up.
- Time to development of seizures as time to event outcome.
- Adverse events (although the EEG may not cause any adverse event per se, adverse events may be related to sedation given to participants and may be transient).
Search methods for identification of studies
We searched the following databases (Appendix 1).
- The Cochrane Epilepsy Group Specialised Register (17 October 2013).
- The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 9, 2013).
- MEDLINE (17 October 2013).
- Clinical Trial Registry (ClinicalTrials.gov (17 October 2013).
Searching other resources
We searched the references of all studies retrieved in full to identify additional research papers. We contacted authors of relevant articles and experts in the field to ask about additional research papers and unpublished trials. We looked for conference proceedings for trials relevant to our review. We decided not to impose language restrictions.
Data collection and analysis
Selection of studies
Dr Pankaj B. Shah (methodology expert (PBS)) and Dr Saji James (content expert (SJ)) carried out the searches (Lefebvre 2009). The methodology expert and the content expert independently carried out an initial screening of the titles of research papers. If papers were believed to be relevant, the review authors independently screened the abstracts. For all articles whose abstracts were found to be relevant, we retrieved the full text. When full-text articles were not available, we contacted the study authors and asked them to provide the full text of the article. We decided to also use the above mentioned search methodology during screening of the cross-references of the full-text retrieved articles and articles suggested by authors and experts in the field. PBS and SJ reviewed the full-text articles independently. After reviewing the research papers, we classified each into one of the following groups.
- Included studies.
- Excluded studies.
- Studies pending decision (if required, authors were contacted to provide additional details of the study).
We recorded the information collected during the above review process on the eligibility assessment form included in Appendix 2.
We attempted to identify duplicate publications by assessing similar study types, same place or same authors (maybe with different sequence). We used reference management software (Mozilla with Zotero) to identify and exclude duplicate publications. In cases of doubt, we contacted the study authors to avoid inclusion of duplicate publications in this review.
We agreed to resolve any disagreements by discussion and to reach a final decision by consensus or by consultation with the Cochrane Epilepsy Group. We used standard methodological procedures expected by The Cochrane Collaboration.
Data extraction and management
We could not extract the data in the present review, as no study met the inclusion criteria. The data extraction process was decided as follows.
- PBS and SJ decided to independently extract required data from the full-text articles of the included studies. (We have included the data extraction form in Appendix 3.) The data extraction form had five components.
- Identification of study.
- Characteristics of included studies—with a brief description in tabular form of methods, participants, interventions and outcomes and notes on specific issues (if any).
- Risk of bias table, as per Cochrane Guidelines (Altman 2008).
- Measurements of treatment effects extracted.
- Information pertaining to any discrepancy noted in records of the clinical trial registry.
- We agreed to resolve any disagreements by discussion and to reach a final decision by consensus or by consultation with the Cochrane Epilepsy Group. We agreed to follow guidelines of a quality of reporting meta-analysis, or QUOROM statement, and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses, (formerly QUOROM) (Moher 2009).
Assessment of risk of bias in included studies
We could not assess the risk of bias in the present review, as no study met the inclusion criteria.
We wanted to report the following bias as recommended in the guidelines for risk of bias tables (Altman 2008; Appendix 4). We agreed to fill the description for each domain with the quote from the article or correspondence and then comment with judgement regarding particular bias (yes, no or unclear); we decided to undertake a summary assessment of risk of bias for each outcome (across domains) within and across studies and to make judgements about the risk of bias as low, unclear or high. We planned to report a risk of bias graph and a risk of bias summary figure. PBS and SJ decided to independently assess the risk of bias. We agreed to resolve any disagreements by discussion and to reach a final decision by consensus or by consultation with the Cochrane Epilepsy Group.
Characteristics of excluded studies: We provided a list of excluded studies with reasons for exclusion in tabular form.
Characteristics of ongoing studies: We could not report in tabular form the details of any ongoing studies in terms of methods, interventions and outcomes or trial registration numbers.
Measures of treatment effect
We could not measure the treatment effect in the present review, as no study met the inclusion criteria. The process of measurement of treatment effect was decided as follows.
We planned to calculate proportions of participants developing seizure after follow-up periods of one month, six months, 12 months and two years. We also planned to calculate risk of recurrence between no EEG and EEG (early EEG, late EEG or any other time), total number of seizure episodes in each group during the two-year follow-up, time to development of seizures as time to event outcome and adverse events (if any). We agreed to use odds ratio for dichotomous outcomes and mean difference for continuous data. We decided to convert extracted data to the above measures for treatment effects, if they were given in other forms. We would extract or calculate 95% confidence intervals for all data. In the case of insufficient information, we would contact study authors to ask for additional details.
Unit of analysis issues
We did not anticipate any unit of analysis issues.
Dealing with missing data
We contacted study authors to ask for missing data such as method of randomisation not stated in the paper or whether the outcome of interest was not reported but has been analysed. The reasons for missing data if found would have helped us with imputation of missing data.
Assessment of heterogeneity
We could not assess the heterogeneity in the present review, as no study met the inclusion criteria. The process of assessment of heterogeneity was decided as follows.
We decided to assess clinical heterogeneity by comparing participant factors, interventional factors, outcome factors and methodological heterogeneity by study methods. We also planned to assess statistical heterogeneity by measuring variability in interventional effects by visually comparing the overlap of confidence intervals on forest plots. If confidence intervals for the results of individual studies had poor overlap, this might have indicated the presence of statistical heterogeneity. We also planned to measure statistical heterogeneity by using the I
- 0% to 40%: might not be important.
- 30% to 60%: may represent moderate heterogeneity.
- 50% to 90%: may represent substantial heterogeneity.
- 75% to 100%: might represent considerable heterogeneity.
Assessment of reporting biases
During this stage, the review authors were to try to find out primary and secondary outcomes of the included studies from the clinical trial registry (if possible) to assess any discrepancy in reporting. If we found any, we were to report them. We agreed to assess funnel plot asymmetry if we identified more than 10 studies. Reasons for asymmetry include publication bias, outcome reporting bias and heterogeneity.
We could not attempt data synthesis in the present review, as no study met the inclusion criteria. The process of data synthesis was decided as follows.
We planned to analyse each trial and record data on the data extraction form. Review authors decided to enter the results of each study independently using The Cochrane Collaboration's Review Manager software (RevMan 2008). We planned to carry out a meta-analysis according to Cochrane guidelines; the most common method available using RevMan is the Mantel-Haenszel (MH) method. If RCTs were clustered, we would have used the inverse method (IV). In case of heterogeneity, we planned to carry out a thorough assessment (Assessment of heterogeneity).
Subgroup analysis and investigation of heterogeneity
We could not attempt the above in the present review, as no study met the inclusion criteria. The process agreed upon was as follows.
We planned to carry out subgroup analyses on the basis of sex, duration of disease, duration of hospitalisation and length of follow-up period. In cases of significant heterogeneity, we might have followed the steps outlined below.
- Recheck extraction and recording of data.
- Change from random-effects model to fixed-effect model.
- Perform sensitivity analysis (Sensitivity analysis).
- Explore heterogeneity by subgroup analysis.
- Present systematic review without meta-analysis.
Sensitivity analysis is a repeat primary analysis in which alternative decisions and ranges of values are substituted for decision making related to assessment of the robustness of conclusions.
We could not attempt sensitivity analysis in the present review, as no study met the inclusion criteria.
We planned to carry out the following steps in a sensitivity analysis.
- Some studies have larger effects than others because
- Random error means that multiple replications of the same study will produce different effect estimates because of sampling variation, even if replications would yield the right answer on average. The results of smaller studies are subject to greater sampling variation and hence are less precise. Imprecision is reflected in the confidence interval around the intervention effect estimate from each study and in the weight given to the results of each study in a meta-analysis. More precise results are given more weight.
- In cases of missing values, use of following imputation methods are suggested.
- Many methods for imputation techniques have been proposed. In cases of dichotomous data, best case-worst case analysis is done, so it is possible to find out how the risk factor or the result value may vary in different situations. For continuous data, the last value takes the role of the missing value. These imputations are important because RCTs have to be analysed as intention-to-treat analyses.
- Use the random-effects instead of the fixed-effect model.
The above sensitivity analyses were prespecified, but it was not possible to specify all sensitivity analyses, as many potential issues might develop only in the course of completing the review. In case sensitivity analysis had an influence on the robustness of the conclusion, we decided to attempt to resolve the uncertainty by contacting trial authors and consulting the Cochrane Epilepsy Group. As it might not be possible to report all sensitivity analyses in detail, we planned to provide a summary table. Sensitivity analysis would have helped us to explore the influence of various factors.
Summary of findings tables
We were to provide Summary of findings tables, prepared with the help of GRADEPro software. We planned to report a rating of overall quality of evidence for each outcome, as well as conclusions, and implications for practice and research (Appendix 5). PBS and SJ agreed to prepare independently the summary of findings. We agreed to resolve any disagreements by discussion and to reach final decisions by consensus or by consultation with the Cochrane Epilepsy Group.
We conducted the review according to the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2008).
Description of studies
Results of the search
With the help of the Trials Search Co-ordinator of the Cochrane Epilepsy Group, 33 potentially eligible studies were identified for this review on 17 October 2013. The summary of the results of the search is included in Appendix 6. After assessing the titles and abstracts, the review authors found no studies for possible inclusion in the review.
None of the studies met the inclusion criteria; thus we did not include any study in the present review.
All studies were excluded because the study design and the intervention were not of interest for this review (Excluded studies).
Risk of bias in included studies
No studies were included in this review, hence the risk of bias is not applicable.
Effects of interventions
In the absence of any suitable studies for this review, analyses were not possible. Although we could not attempt the data collection and analysis as it was decided in the protocol, we decided to describe the process of different aspects of data collection and analysis, as the review will be updated regularly and the full protocol may not be easily accessible to all users of this evidence.
We could provide no summary of findings table in the present review, as no study met the inclusion criteria.
Summary of main results
We did not find any randomised controlled trials of EEG for children with complex febrile seizures. Hence currently no randomised high-quality evidence can be reported for an EEG and its timing after complex febrile seizures in children younger than five years of age.
Overall completeness and applicability of evidence
A comprehensive search of the literature was done as described in Appendix 6, and a number of studies that may be relevant to the review were assessed. No randomised controlled trials were identified.
Quality of the evidence
It is very difficult to comment on the quality of evidence, as none of the studies met the inclusion criteria.
Potential biases in the review process
Agreements and disagreements with other studies or reviews
No other similar review has been conducted. However, a few published non-randomised studies to date have looked specifically at CFS and the role of EEG in its evaluation (Joshi 2005; Maytal 2000; Yucel 2004). In a retrospective review of 33 neurologically normal participants with EEGs within one week of CFS, Maytal et al found none with abnormalities, but Yucel et al reported abnormalities in 71 of 159 children with CFS analysed retrospectively over seven years. In the latter group, 16 were noted to have abnormal EEG records in the first week. Of 71 participants with abnormal EEG records, 51 were diagnosed with epilepsy on follow-up. One other study by Joshi et al showed that children with CFS are approximately 3.5 times more likely to display an abnormal EEG within seven days post ictus in comparison with children with CFS in whom the EEG was performed beyond the seven-day period post ictus. Hence, conflicting reports describe the utility of EEG and its timing after complex febrile seizures among children.
Implications for practice
Implications for research
This review has highlighted the absence of randomised controlled trials investigating the utility of EEG and its timing after complex febrile seizures in children. We found no RCT as evidence to support or refute the utility of EEG and its timing after complex febrile seizures among children. A randomised controlled trial can be planned in such a way that participants are randomly assigned to an EEG group and a non-EEG group with sufficient sample size. Hence well-designed randomised controlled trials are required to confirm the same. These clinical trials should follow good clinical practice (GCP) guidelines with important stress on methodological issues such as randomisation, blinding of outcome assessment, intention-to-treat analysis and scientific means to reduce the bias.
Updating the review: In accordance with Cochrane policy, we plan to update the review every two years (or sooner, should we find any important study that fulfils the inclusion criteria).
We would like to thank the following.
- The Cochrane Epilepsy Group for valuable guidance provided.
- The Indian Council of Medical Research and the South Asian Cochrane Network and Centre, Prof BV Moses and the ICMR Centre for Advanced Research and Training in Evidence-Based Healthcare and CMC Vellore for supporting the training program and makingThe Cochrane Library free for India.
- Prof Prathap Tharyan, Director, South Asian Cochrane Network and Centre, Prof BV Moses and the ICMR Centre for Advanced Research and Training in Evidence-Based Healthcare and CMC Vellore for guidance provided during the training workshop.
- Management, Vice Chancellor, Deans, HOD and Faculty members of our departments of SRU for continuous inspiration and support.
- Family members for continuous inspiration and support.
Data and analyses
This review has no analyses.
Appendix 1. Search strategy
EEG for children with complex febrile seizures
1 Epilepsy Specialised Register 17 October 2013
#1 MeSH DESCRIPTOR Seizures, Febrile Explode All WITH BL CF CI CL CO CN DI DH DT EC EM EN EP EH ET GE HI IM ME MI MO NU PS PA PP PC PX RA RI RT RH SU TH US UR VE VI
#2 (febrile seizure*) or (febrile convulsion*) or (pyrexial seizure*) or (pyrexial convulsion*) or (fever seizure*) or (fever convulsion*)
#3 #1 OR #2
#4 MeSH DESCRIPTOR Electroencephalography Explode All WITH AE CL CT DE EC ES HI IS MT MO NU PX RE ST SN TD UT VE
#5 electroencephalograph* or EEG
#6 #4 OR #5
#7 #3 AND #6
#8 #3 AND #6 AND INREGISTER AND >2011:YR
2 CENTRAL, Issue 9, The Cochrane Library, September 2013
#1 MeSH descriptor: [Seizures, Febrile] explode all trees
#2 (febrile seizure*) or (febrile convulsion*) or (pyrexial seizure*) or (pyrexial convulsion*) or (fever seizure*) or (fever convulsion*)
#3 #1 or #2
#4 MeSH descriptor: [Electroencephalography] explode all trees
#5 electroencephalograph* or EEG
#6 #4 or #5
#7 #3 and #6 from 2012, in Trials
3 MEDLINE (Ovid) 1946 to 17 October 2013
1. (randomized controlled trial or controlled clinical trial).pt. or (randomized or placebo or randomly).ab.
2. clinical trials as topic.sh.
4. 1 or 2 or 3
5. exp animals/ not humans.sh.
6. 4 not 5
7. exp Seizures, Febrile/
8. febrile seizure*.tw.
9. febrile convulsion*.tw.
10. pyrexial seizure*.tw.
11. pyrexial convulsion*.tw.
12. fever seizure*.tw.
13. fever convulsion*.tw.
14. 7 or 8 or 9 or 10 or 11 or 12 or 13
15. exp Electroencephalography/
16. (electroencephalograph* or EEG).tw.
17. 15 or 16
18. 6 and 14 and 17
19. limit 18 to ed=20121001-20131017
Appendix 2. Eligibility assessment form
Name of the review author: Date:
Title of the study: Study ID:
Name of the authors of the study:
Name of the journal with year of publication:
Final decision: Include Exclude Unclear Pending
1. Reasons for excluding the study:
2. In case study is labelled as “unclear”- Contact the authors __________ date:
3. In case study is labelled as “pending”- Contact the authors ___________date:
4. Response of the author: ___________________ date:
5. Opinion of Cochrane Epilepsy Group sought:___________________ date:
6. Opinion of Cochrane Epilepsy Group: _________________________ date:
Appendix 3. Data extraction form
1. Response of the author sought: ___________________ date:
2. Response of the author: ___________________ date: _________________________
3. Opinion of Cochrane Epilepsy Group sought:___________________ date:______________
4. Opinion of Cochrane Epilepsy Group: _________________________ date:___________________
Appendix 4. Risk of bias tool
Appendix 5. Summary of findings table
The GRADE approach describes levels of quality of a body of evidence as follows.
Factors that would have reduced the quality of the evidence include the following.
Factors that would have increased the quality of the evidence include the following.
For example, if we would have found that the results were precise, we would have chosen 'no' in GRADEPro software. If serious imprecision was present, we would have chosen four and downgraded by one level in the GRADEPro software. If very serious imprecision was present, we would have chosen 'very serious', and this might have led to downgrading of the quality of evidence for the particular outcome by two levels. A footnote in the summary of findings table would have documented this.
Appendix 6. Summary of the results of the search
The following table describes the summary of the results of the search for the review.
Contributions of authors
Develop search strategy: PBS, SJ with Trials Search Co-ordinator.
Search for trials: PBS, SJ with Trials Search Co-ordinator.
Obtain copies of trials: PBS, SJ and SE with Trials Search Co-ordinator.
Select trials to include: PBS, SJ and SE.
Draft the final review: PBS, SJ and SE.
Declarations of interest
Sources of support
- None, Not specified.
- None, Not specified.
Differences between protocol and review
We could not attempt the data collection analysis and summary of findings table, as no study met the inclusion criteria. We decided to describe the process of different aspects of data collection and analysis in the present review, as the review will be updated regularly and the full protocol may not be easily accessible to all users of this evidence.
Medical Subject Headings (MeSH)
MeSH check words
Child, Preschool; Humans