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European Journal of Neurology 2004, 11: 800–810

CME ARTICLE

A systematic review of the epidemiology of status epilepticus
R. F. M. China,b, B. G. R. Nevillea and R. C. Scotta,c
a

Neurosciences Unit, Institute of Child Health, University College London, London, UK and Great Ormond Street Hospital for Children NHS

Trust, London, WCIN IEH, UK; bThe Centre for Paediatric Epidemiology and Biostatistics; and cRadiology and Physics Unit, Institute of Child Health, University College London, London, UK

Keywords:

epidemiology, status epilepticus, systematic review
Received 8 March 2004 Accepted 13 May 2004

Population-based data on the incidence, aetiology, and mortality associated with status epilepticus (SE) are required to develop preventative strategies for SE. Through a systematic review, we aimed to assess the methodological quality as well as similarities, and differences between available population based studies in order to arrive at conclusions on the epidemiology of SE. All population-based studies where primary outcome was incidence, aetiology or mortality of SE were identified through a systematic search and synthesized. Methodological quality of studies were independently rated by two examiners using a unique scoring system. Seven population-based projects on SE yielding nine published reports and five abstracts were reviewed. Quality scores were in the range of 19–34 with a possible maximum of 40 (kappa scores 0.67– 1.0). The incidence of SE has a bimodal distribution with peaks in children aged less than a year and the elderly. Most SE were acute symptomatic. Short-term mortality was 7.6–22% and long-term mortality was 43%. Age and aetiology were the major determinants of mortality. There are few population-based studies on SE but most are of good quality. Most studies are primarily or exclusively based on adult populations. There is limited information on the association of ethnicity and socio-economic status and SE.

Introduction
Data on the incidence, aetiology, and mortality associated with status epilepticus (SE), the most common medical neurological emergency (Leppik, 1985; DeLorenzo et al., 1995, 1996), are required for decisions on allocation of resources by institutions, and even government, that may be used to develop primary and secondary preventative strategies for SE. Most published data are from hospital-based studies and may therefore be biased and inappropriate. What is required is epidemiological data from the general population, and such data may be obtained through population-based studies. Through a systematic review, we aimed to assess the methodological quality as well as similarities, and differences between available population-based studies in order to arrive at conclusions on the epidemiology of SE. The advantages of a systematic review rather than a traditional review have been well described previously (Mulrow, 1987). On the whole, systematic reviews have been conducted for randomized controlled trials (RCTs) as they have long been viewed as the Ôgold standardÕ of evidence; observational studies have been
Correspondence: Richard F. M. Chin, The Wolfson Centre, Mecklenburgh Square, London WC1N 2AP, UK (fax: +44 2078339469; e-mail: r.chin@ich.ucl.ac.uk).

largely overlooked. This has resulted in the development of methodology for systematic reviews, mainly for RCTs. However, in some situations, only data from observational studies, such as epidemiological studies, are available, possible or appropriate (Berlin, 1995). Observational studies have been used to evaluate educational programmes (Sipe and Curlette, 1997) and assess risk factors for disease (Ioannidis and Lau, 1999). Studies on the latter may not be randomized because the risk factors may be related to intrinsic human practices, and it is unethical to expose subjects to harmful risk factors (Lipsett and Campleman, 1999). Thus, it is increasingly being realized that observational studies provide useful evidence, resulting in more recent, active development of methodologies for systematic reviews of observational studies (Mulrow et al., 1997; Sutton et al., 1998; Stroup et al., 2000). The specific aim of this systematic review is to identify and synthesize all available population-based data on SE to arrive at conclusions on the epidemiology of SE including: • The incidence of SE worldwide, and the effect of gender, ethnicity and age on incidence. • The range of aetiologies of SE. • The association of SE with epilepsy. • The recurrence of SE. • The mortality associated with SE.

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Ó 2004 EFNS

Step 4: The conference proceedings and abstracts of the British Paediatric Neurology Association (BPNA). European Paediatric Neurology Society (EPNS) year 1995 to year 2003 were handsearched. classification of seizure type and adjustment of rates. 1993) (see Table 1). or mortality of SE were included. definitions. Data extraction and assessment of study quality Data to be extracted were agreed by two of the authors and included study period. Using the scoring system.. Step 3: An internet search up to 31 December 2003 using Google as the search engine using the search strategy in step 1 was conducted. Thus.M. and outcome measures.M. adequacy of case definitions.C.C. and R. Cochrane Collaboration database. and non-primary studies were excluded.S. Studies of all age groups were included.C. the American Epilepsy Society (AES).F. Studies that were based in a single institution or did not involve a network of hospitals serving a well-defined general population. each study was assessed independently by two reviewers (R.). Selection criteria Methodological definitions in individual studies Inclusion criteria for selection of cases of SE from study population Seizure type defined according to the ILAE guidelines? Risk factors/aetiology defined according to ILAE guidelines? Definitions of outcome parameters Standardization of rates/ratios Ascertainment adjustment Maximum score ¼ 40. Embase. classification of seizure types. To assess the methodological quality. Step 2: The reference list of articles identified in step 1 were examined to identify additional relevant studies. these items were given greater scores. minimum score ¼ 11. In accordance with the ILAE guidelines for epidemiologic studies on epilepsy. 2000) and the guidelines for epidemiologic studies on epilepsy of the International League Against Epilepsy (ILAE) (International League Against Epilepsy. type of rate/effect/impact. and whether there were adjustments for degree of ascertainment. definition of seizure types and aetiologies according to the ILAE guidelines.) extracted the data using a data extraction form and a second reviewer (R. and CINALH for papers published between 1966 and November 2002 using the following search terms: • status epilepticus and population* • status epilepticus and epidemiology • status epilepticus and incidence • status epilepticus and aetiolog* • status epilepticus and etiolog* • status epilepticus and cause* • status epilepticus and seizure type • status epilepticus and mortality • status epilepticus and fatality All of the above searches were repeated with prolonged febrile convulsion* or prolonged febrile seizure* instead of status epilepticus. Commission on Epidemiology and Prognosis. aetiology. details of the study population. adequacy of definition of outcome measures. All the searches were combined with (or stepwise limits conducted in Medline): (i) review (ii) meta-analysis. description of study population.) confirmed them.F. definitions of cases and outcomes. Web of Science.S. validation of the databases. the more important determinants of quality were considered to be type of study design. One of the reviewers (R. Inter-rater agreement (kappa Ó 2004 EFNS European Journal of Neurology 11. Each study was scored on the following items: type of study design. selection criteria of study population. we developed a scoring system based on a published proposal for reporting meta-analysis of observational (Stroup et al.A systematic review of the epidemiology of status epilepticus 801 Methods Search strategy Table 1 Scoring system for assessment of methodological quality of population-based studies on SE Study design Sample size 12 ¼ prospective 5 ¼ retrospective 2 ¼ clearly defined 1 ¼ unclearly defined 0 ¼ not defined 4 ¼ all clear 2 ¼ most clear 1 ¼ most not clear 4 ¼ clear 2 ¼ not clear 1 ¼ not defined 4 ¼ clear 2 ¼ not clear 1 ¼ no 4 ¼ clear 2 ¼ not clear 1 ¼ no 2 ¼ all clear 1 ¼ most clear 0 ¼ most not clear 4 ¼ either age-specific or age-adjusted as well as sex-specific 2 ¼ age-specific or age-adjusted or sex-specific 1 ¼ crude only 4 ¼ clear 1 ¼ not clear/none The following steps for ascertainment of the appropriate articles for review were carried out: Step 1: Computer-assisted literature searches of the bibliographic databases: Medline. seizure types. 800–810 .C. All population-based studies on SE where the primary outcome was either the incidence. selection criteria.

Children less than a year of age had the highest incidence (135–156/100 000/year) (DeLorenzo et al. P < 0. USA.. Age and aetiology of SE were the major determinants of short. 1996. 2001). methodological quality scores and inter-rater agreement are shown in Table 2. North London Groups).6–2.0).. Knake et al. and North London Group.. 1998. The standardized mortality ratio (SMR). Chin et al. 2003). In the paediatric population. All prolonged febrile convulsions (PFC) were shorter than 2 h (Hesdorffer et al. 1998. Louis Groups) and one was prospective (Richmond Group). No deaths Ó 2004 EFNS European Journal of Neurology 11. All studies were conducted after the ILAE’s guidelines for epidemiologic studies were published. Chin et al. Mortality associated with SE across all age groups ranged from 7. see Table 3.. 2001).. cerebrovascular disease/accidents. A glossary of definitions used in the studies is listed in the Appendix. Logroscino et al. In contrast. Rochester Group.802 R. The quality scores ranged from 19 to 34 of a possible maximum of 40. 1998). In adults.. 1996. 2002. USA.. C. 2001). 1996. California. 2002). 1998). The results are presented for data collection up to 31 December 2003. Towne et al. 2000. California Group. Chin et al. 1995. Recurrence was highest in the paediatric population (DeLorenzo et al. 2001. Minnesota. Logroscino et al.. in adults. whilst in adults.. 2000. 1999).. 1996. Recurrence of SE occurred in 13.1 (95% CI 2.2 (95%CI 1.. UK) yielding nine published reports (DeLorenzo et al. 2003) and low antiepileptic drug levels (21%) (DeLorenzo et al. Knake et al.9). B. Studies were pooled only when their definitions of relevant variables were similar or the results could be processed and analysed as such. Results Seven population-based projects on SE (Richmond Group.. the relative risk of mortality compared with the general population. Waterhouse et al. Hesdorffer et al. F... as were those of non-white ethnicity. USA. for subjects with long-term mortality associated with SE was 2. 800–810 . Chin et al. Virginia.. St Louis Group.6 to 22% during hospitalization for SE or within 30 days of SE (short-term mortality) and 43% within 10 years following initial survival 30 days after SE (long-term mortality).. Hesdorffer et al. Knake et al. almost all (93. 2003).. Coeytaux et al. Hessen Group. Trevathan et al.5% (DeLorenzo et al. R.. Description of the studies The description of the studies. prolonged febrile convulsions (33–35%) (Hesdorffer et al. In contrast. adults had no difference in duration of continuous SE (median 97. The remaining three population-based projects were European-based and prospective (Hessen. Knake et al.. In children.. withdrawal or low levels (34%) of maintenance antiepileptic drugs were most likely. 2002. Acute symptomatic SE accounted for most aetiologies across all age groups..5 min) was shorter than that of intermittent SE (median 87 min.. Knake et al. Frenchspeaking Cantons. 2001). Hesdorffer et al. In children. and in those <65 years. 2003a) fulfilled the inclusion criteria for entry into the review. Hesdorffer et al.. 1997.5). Most deaths during hospitalization for SE or within 30 days of SE occurred in those with an acute symptomatic aetiology (DeLorenzo et al. Mortality is lowest in children (short-term mortality from 3 to 9% and long-term mortality around 7%) and highest in the elderly (short-term mortality from 22 to 38% and long-term mortality 82%). 2001. St..... Status epilepticus occurred within the context of epilepsy in <50% of cases overall. Four projects were conducted in the USA. those aged <1 year had the highest short-term mortality (17–18%) (Morton et al. 2003. G. USA. Inter-rater agreement was good to very good with kappa scores between 0.. Amongst children.02). The cause of SE varied according to age groups.. Seizure characteristics The incidence of SE showed a bimodal distribution with peaks in children less than a year of age and the elderly (DeLorenzo et al. three of which were retrospective (Rochester.. SMR was 5. Scott scores) for assessment of quality-of-study methodology was determined for each study. 1998. Most SE lasted <24 h (DeLorenzo et al.8 (95% CI 2. 1998.5 min) compared with intermittent SE (median 85 min) (Waterhouse et al. 1996)... males were more likely to have SE. 1998. Switzerland. The percentage of SE patients with a history of epilepsy was higher in those who resided in rural areas (49–56%) compared with those who resided in urban areas (33%) (Coeytaux et al.. 1996. 2001..and long-term mortality. 1996. 16–38% had a history of epilepsy. The SMR in those older than >65 years was 2. 1999. Hesdorffer et al. 2002) and five abstracts (Morton et al. There were neither systematic reviews nor meta-analyses. 1996) were most common. 1996. 2002.. Germany.8–8. 2001). Wu et al. Chin. For further details. Neville and R..67 and 1.. French-speaking Cantons Group. 1997. the duration of continuous SE (median 60.. Wu et al. Few episodes of SE were idiopathic (see Table 4 for further details on aetiology). M. 42–50% had a history of epilepsy (DeLorenzo et al. In general.0..1–3. Scott et al.3–18.8%) patients with recurrences had a history of epilepsy (Knake et al.

0 1. 1997 Hesdorffer et al. Displayed scores are that of one of the authors (RCS). 2885 children Prospective Prospective Retrospective Prospective Prospective 598 children 318 adults 39 649 subjects 55 children 79 children Most Most Most Most Most clear clear clear clear clear Clear Clear Clear Clear Clear Clear Clear No Clear Clear Unclear Unclear No Unclear Unclear Clear Clear Clear Clear Clear Most clear Clear Most clear Clear Clear No Clear No Clear Clear 132 130 433 108 150 adults. (2003a) Chin et al. adults.. (2002) Wu et al. ILAE SE type and ILAE aetiology refer to whether the types of SE and aetiology of SE were classified according to ILAE guidelines. (2002) USA USA Abstracts Morton et al. (2002) Trevathan et al.Table 2 Description. Maximum methodology score ¼ 40. 803 . Methods definitions refers to definitions outlined in the methodology of individual studies.and sex-specific Age-adjusted and sex-specific Age.. (1999) Coeytaux et al. Outcome refers to whether the outcome parameters were clearly defined or not. minimum score ¼ 11. Inclusion criteria refers to the criteria for selection of cases of SE from study population. Note that the authors of this paper are also the authors of the last two abstracts in this table. (2001) Towne et al. 1998 Waterhouse et al. 1996) Logroscino et al. methodology scores and interrater agreement of population-based studies on the epidemiology of status epilepticus Studies Country Design Sample size Methods Inclusion ILAE ILAE Standardization definitions criteria SE type aetiology Outcome of rates/ratios Ascertainment Methodology adjustment score j-value Ó 2004 EFNS European Journal of Neurology 11. adults 52 children 69 children 212 children 64 children Most Most Most Most Most clear clear clear clear clear Clear Clear Clear Unclear Unclear Clear Clear Clear Clear Clear Clear Clear Unclear Unclear Unclear Clear Clear Clear Clear Clear Published papers DeLorenzo et al.78 0.89 1. (2002) Scott et al.and sex-specific Age. Standardization of rates/ratios refers to whether rates/ratios were standardized and the type.0 0.78 USA USA USA Switzerland Germany Logroscino et al.0 0.and sex-specific Crude Age.67 1. 29 children Most clear Unclear Clear Unclear Clear Age-specific Age. (2003) USA USA USA UK UK Crude Crude Age-specific Crude Crude Unclear Unclear No Clear Clear 31 31 22 33 33 0.0 A systematic review of the epidemiology of status epilepticus Methodology scores are based on the scoring system detailed in Table 1.0 1. adults. 800–810 USA Retrospective Retrospective Prospective Prospective Prospective Retrospective 110 adults. Ascertainment adjustment refers to whether an adjustment was made for degree of ascertainment. 35 children Retrospective 12716 adults.78 1.0 0.78 0. adults. (2001) Prospective 137 adults. (1995.67 1. (2000) Knake et al.and sex-specific Crude Clear No No Unclear No Clear No No 32 28 28 31 31 34 28 19 0.

8* – – 3.3. The remaining five studies that reported incidence rates had similar quality scores which were high (DeLorenzo et al.3 : 1 2.. the SMR was significantly elevated in the acute and remote symptomatic SE groups.8 17. The range of reported crude incidence rates is wide (6. B. the ILAE published guidelines for epidemiologic studies on epilepsy (International League Against Epilepsy.9–41/100 000/year).and long-term mortality. A similar methodology has been used in a recently published systematic review of incidence studies of epilepsy (Kotsopoulos et al. 2000) and the ILAE’s guidelines (International League Against Epilepsy. Ethnicity had no effect on short-term mortality.. It may be hypothesized that problems in case ascertainment between studies may partly explain the wide range of reported incidence rates.6 : 1 <5 *Restricted to generalized convulsive status epilepticus.4% in continuous SE compared with 19.01). 95% CI 1.86 4. Stroup et al. Waterhouse et al.6% in intermittent SE (P < 0. and guidelines for systematic reviews of qualitative studies (Abou-Khalil et al.. 2002). Hesdorffer et al. F. 2001) but despite this there was still a wide range of incidence rates (9. Commission on Epidemiology and Prognosis. 1993). R. 1998. Amongst seizure types.8/100 000/year in California. The lowest incidence rate is from a study with a low methodology score (Wu et al.6 1:1 2:1 <5. Quantification of Ó 2004 EFNS European Journal of Neurology 11. C. Knake et al.0. 2002) but there was increased long-term mortality in subjects with SE >24 h when compared with those with SE <2 h (RR 2.3 24 6 62 2:1 – <1. Differences in definitions. This suggests that the true incidence rate of SE is higher than the 6.9 – 10.804 R. The effect of duration of SE and gender on shortterm mortality is uncertain (Logroscino et al. In an attempt to address this issue. It is interesting that studies that had the largest study sample size (Trevathan et al... and aetiologic criteria in epidemiological studies on epilepsy have often yielded discordant results between studies. we were able to assess the methodological quality of studies and to compare studies. 2002) had the lowest methodology scores.. M.. short-term case fatality was 31. Discussion The methodology for systematic reviews of non-interventional research is still in its infancy. Thus. Commission on Epidemiology and Prognosis.58 14. There was no difference in short-term case fatality between continuous and intermittent SE in children. a meta-analysis of the data from these studies was not possible but through the development of a unique scoring system based on a published proposal for reporting meta-analysis of observational studies (Stroup et al. Chin. Neville and R. 1996. >60 Rochester (Minnesota. Coeytaux et al. myoclonic SE in particular was associated with high short. Scott Table 3 Incidence of SE according to research groups Incidence rate (per 100 000 persons/year) Crude Ascertainment adjusted Age-adjusted In Children In adults In the elderly Male : Female White : Non-white Peak age (years of age) Richmond (Virginia.3–13).1–5. in 1993. >65 Hessen (Germany) 15. 1993.. 95% CI 1. and have made comparison of results difficult (International League Against Epilepsy. 1993). Wu et al. but in adults.. USA) – – 18. 1997. Commission on Epidemiology and Prognosis.. classification of seizures.. We identified seven projects with 13 eligible studies that were available for this systematic review.1 17. there is still heterogeneity in the basic epidemiological parameters listed above. 2000). 2002). In subjects with longterm mortality. Subjects with myoclonic SE had a significant relative risk (RR) of long-term mortality in comparison with those with generalized SE (RR 4.1) (Logroscino et al. G.8–41/100 000/year). Most populationbased studies on SE have high methodology scores.. 1993). >60 North London (UK) – 18 – – 1.. occurred in those with PFC. 1999. In this systematic review of observational studies.1 – 4 54 2:1 – >60 French-speaking Cantons (Switzerland) 9..3 21 5 15 2:1 – California (USA) 6. USA) 41 61 – 38 27 86 – 3:1 <1. 2000. Although they were conducted after the ILAE’s published guidelines for epidemiologic studies on epilepsy. 2002. suggesting that sample size alone is not an adequate guide to the quality of any individual study. 2002). 800–810 . the methodology has been based on recently published proposals for reporting meta-analyses of observational studies.. Wu et al. Acute symptomatic SE was associated with a higher mortality rate than idiopathic/cryptogenic SE.

Two studies have reported this sub-group as a distinct category (Hesdorffer et al. the age adjusted incidence of SE in the white population in Europe and the USA is approximately 20/100 000/year with higher incidence in early childhood and in the elderly.and sex-specific rates should be provided wherever possible.. Verity and Golding. the reported ascertainment-corrected incidence in the Richmond study is still three times that of the Hessen study (see Table 3 for further details). Although the definition of SE was similar in all studies. and if summary frequency indexes are reported. similar quality scores.. took underascertainment into account and reported ascertainment corrected rates. Chin et al. 1993). The recognition of PFC as a distinct category is important as there is evidence that suggests that the natural history of febrile seizures may be different from that of other acute symptomatic causes of SE.. The effects of socio-economic. 1978. categorized PFC under acute symptomatic causes in accordance with the ILAE guidelines. These results suggest that case ascertainment may not be the only explanation for the wide incidence range. 2000). and a higher incidence being reported in non-white subjects relative to white subjects. Standley et al.A systematic review of the epidemiology of status epilepticus 805 ascertainment was not determined in the Swiss study (Coeytaux et al. Males are twice as likely as females to have an episode of SE. mortality is less. 2003b). Hessen. and it is possible that their reported crude incidence of 9.. Epidemiological studies in countries with limited resources have found a higher incidence of epilepsy than developed countries but there are no such studies on SE. similar degrees of ascertainment. NCSE only accounted for up to 6% of SE cases in studies that included both types of SE. Abou-Khalil et al. Rochester. standardized rates and ratios are very important. The Swiss study. intellectual outcome is better. most subjects who have an episode of SE are previously neurologically normal. All other studies that included PFC. it is unclear from the Richmond Group whether ÔinitialÕ cases used to calculate incidence refer to cases with a lifetime first episode of SE. However. This is reflected in the ILAE’s guidelines for epidemiologic studies.. which has one of the lower reported rates. and Swiss studies included convulsive (CSE) and non-convulsive SE (NCSE) while the Californian and London studies excluded episodes of NCSE. The most common aetiology of SE is an acute symptomatic cause and thus. The Richmond. If it is the latter. Scott et al. and the risk of developing epilepsy is less in subjects with PFC compared with those with other acute symptomatic SE (Ellenberg and Nelson. the Hessen and Rochester studies had similar ascertainment methodologies. Verity et al. There is a sub-group of such subjects whose SE is due to PFC. and environmental conditions on the incidence of SE are not known and studies examining these effects are needed to increase our understanding of SE worldwide.. The Richmond group partly attributed its much higher incidence to its greater non-white racial composition compared with other study areas. a particular form of SE that occurs in children aged from 6 months to 5 years accompanied by fever without central nervous system (CNS) infection (Appleton et al.. Ó 2004 EFNS European Journal of Neurology 11. However. there is a longstanding hypothesis that PFC may cause mesial temporal sclerosis. children with PFC are an important population to study and PFC cannot be considered a completely benign event (Scott et al. 1995). Therefore. 1956. 1989. Despite this. 1991. 1998. 2002. The challenge for the future will be to develop appropriate preventative and/or early intervention strategies to minimize the morbidity and mortality associated with SE.. PFC make up a significant proportion of SE in childhood accounting for up to a third of SE in children. 2002). cultural.. 1995. Overall. which recommends that age.. Therefore. then adjustment to a well-defined and accessible specified population should be made. The London study has also reported a higher incidence in non-white subjects. Maytal et al. Kneen et al. 800–810 . However. It is also possible that the difference is partly explainable by a different age and or sex composition of Richmond compared with other study areas. difference in inclusion criteria may partially explain the diversity in incidence rates. the most common structural substrate for temporal lobe epilepsy requiring surgical intervention(Cavanagh and Meyer.. Some studies in this systematic review do not report these standardized rates and is reflected in their quality scores (see Table 2). 1993). This gender difference may be partly because of a higher incidence of certain aetiologies including cerebrovascular disease and brain trauma in males. 2000. The retrospective nature of the Rochester study suggests that their reported incidence of 18/ 100 000 persons per year may also be an underestimation. In order to take into account differences in the composition of populations and to facilitate analysis of trends over time. but it may reflect a possible role of hormonal influences in the termination of seizures (Moshe et al. 2003). or first SE during the study period. inclusion criteria differed between studies. then the reported incidence may be an overestimate and a more accurate incidence may be closer to that reported by the Rochester and Hessen Groups. 2001.9/100 000/year may have been an underestimate because of incomplete ascertainment.. excluded patients with post-anoxic encephalopathies which accounted for 10% of cases in the Rochester study.

Ó 2004 EFNS European Journal of Neurology 11. then there is a potential danger of the continuation of SE without convulsions detectable only by EEG as described by Treiman et al. but this difference is likely to be due to the follow-up period. continuous EEG monitoring may be very important in guiding the treatment of SE and reduce its associated morbidity and mortality. Patients who received an adequate initial dose of emergency antiepileptic drugs (AEDs) were more likely to have seizure termination but patients were frequently given inadequate doses of emergency AEDs. In addition animal and hospital based studies suggest that longer duration causes brain damage (Aicardi & Chevrie 1970. 1989. and less than half of these would have had a history of epilepsy. Waterhouse et al. (2001) also reported two other main observations on the treatment of SE. 2001). it is important to note that there is experimental data from animals which suggest that longer duration of SE is associated with worser outcome (Meldrum and Brierley..806 R. Cascino et al. 800–810 . 1980. 2000. the relative risk of SE in subjects from rural areas with a history of epilepsy compared with those from urban areas is needed. 1988. A greater proportion of adults with SE had a history of epilepsy compared with children but this may have been due to the small number of children in studies. comparing four treatments for generalized CSE. 1973). Two studies of similar methodological quality reported contrasting findings (Logroscino et al. Moreover. G. Scott Up to 50% of all incident episodes of SE occur within the context of epilepsy. The second possibility is that occasional seizures may occur far more frequently in the form of SE than previously recognized. 1979). Cascino et al. These data suggest that the likelihood of recurrence is greatest in the first 2 years after incident SE and occurs in approximately 2% of patients. 1989. data from population-based studies on SE can provide information on the morbidity attributable to SE providing the research methodology is able to detect such downstream consequences. the onset of SE may not be observed and in the absence of continuous electroencephalographic (EEG) monitoring. If longer duration of SE in human beings is associated with worser outcome. M. In the former. this observation may only reflect a higher percentage of people with epilepsy living in rural areas. Two studies reported that a significant proportion of patients were not treated prior to arrival to hospital (Coeytaux et al. as of all cases of SE associated with epilepsy. In the Veterans Affairs Study. Other studies examining the treatment of SE. 1994). However. Thus. the determination of duration of seizures in observational studies is difficult and conclusions on its effect on SE from these types of studies should be interpreted with caution. it was up to 30 years after incident SE compared with a follow-up of up to 2 years in the latter. F. with the notable exception of PFC (Aicardi & Chevrie 1970. 1997. Neville and R. 2001). Sung and Chu. primary and secondary SE prevention strategies need to be tailored towards specific populations. 1998). As mentioned above. In our search of the literature.. Thus. 65% of patients with subtle SE died within 30 days of SE. Although a higher percentage of SE in subjects who reside in rural areas had a history of epilepsy compared with those who reside in urban areas. In theory. data on the treatment regime for SE on an epidemiological background were sparse.. 1988. R. including the treatment in children. C. The first possibility is that a significant proportion of cases of epilepsy start with SE. as delayed treatment may increase the frequency of SE (Knudsen. 1999) was prospective and had a larger sample size. B. Shorvon. Meldrum and Horton.. are needed for comparison. Chin. The data from this systematic review concurs with hospital-based studies that age and aetiology are the most important determinants of short-term case fatality in SE.. Dunn.. (1987). This is significant. Data from the Rochester study supports this possibility.. The efficacy and safety of benzodiazepines in the treatment of SE in adults in the out-of-hospital setting has been demonstrated in a large randomized controlled study in adults (Alldredge et al. compared with 27% of patients with overt SE (Treiman et al. The Rochester Group reported a recurrence nearly one and a half times as great as in the Richmond and Hessen studies. but the above data would suggest that early treatment with adequate doses of benzodiazepines in the out-of-hospital setting may be important. 1998). 1999). morbidity attributable to SE was excluded from this review. Recurrence of SE occurred in less than 20% of cases but was highest in subjects with a history of SE. there may be uncertainty about the cessation of seizure activity particularly when seizure control requires ventilatory support. Aminoff and Simon. The influence of duration on short-term case fatality is less clear. the problems of measuring attributable cognitive and behavioural problems are many. This raised two important possibilities. the Richmond GroupsÕ study (Waterhouse et al. and may be better addressed by studies of specific subgroups with specific syndromes within SE where the confounding factors can be minimized. Yager et al. Therefore. Maytal et al.. To determine a true difference. Thus. Therapeutic regimes may affect outcome by reducing seizure length. SE was the first unprovoked seizure or the second seizure leading to a diagnosis of epilepsy in two-thirds of cases (Hesdorffer et al. However... Children have a low case fatality and acute symptomatic causes are associated with the worst prognosis. In their retrospective study.

Conclusions There are few population-based studies on SE but most studies are of good quality. This study group.. The effect of duration of SE on mortality and morbidity remains unclear. particularly in the unprovoked group. there is limited information on the association of ethnicity on SE and virtually none on the associations between socio-economic. adults. Alldredge BK. Andermann F. Am J Med 69:657–666. PFC occurs only in children and may account for up to a third of cases of SE in childhood (see Table 4). Chevrie JJ (1970). Together. The study had low power and was conducted in a homogenous white middle class population thus limiting the generalization of its findings. supple- mented by more detailed studies on sub-groups within the same population are needed. Dunn. 1973. Appleton R. The long-term SMR for symptomatic SE was significantly elevated. the increased risk of death is partly related to a generally high risk of death from any cause in that population. Whitehouse W (2000). primarily addressing a purely paediatric population. Acknowledgements Rod Scott is supported by the Wellcome Trust. 800–810 . clinical features and consequences in 98 patients. total. The available data suggests that there are differences in incidence. the Rochester group. the SMR in those older than 65 years was only twofold in comparison with fivefold in those under 65 years. Choonara I. Causes. Temporal lobe epilepsy after prolonged febrile convulsions: excellent outcome after surgical treatment.. and mortality is lower in children. N Engl J Med 345:631–637. Of note. Research at the Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust benefits from R&D funding received from the NHS Executive. Population-based studies primarily addressing the paediatric population. References Abou-Khalil B. C. Continuous SE was associated with higher fatality than intermittent SE. found that duration had no effect on short-term mortality but longer durations were associated with higher long-term mortality. A. Olivier A. an ongoing study. Gelb AM. Martland T. 2002). Andermann E. Early. aetiology and outcome between children and adults. these data suggest that SE is associated with increased mortality after initial survival but in the elderly. children. Isaacs SM et al. there are limited data in these studies on PFC. Like in short-term fatality. T. and this may be an important distinction to make in describing seizure types in SE. children fared better than adults and the elderly are at particular risk. Phillips B. A study of 239 cases. In addition. most studies eligible for this review were on primarily or exclusively adult populations and therefore paediatric results may not reflect the ÔtrueÕ epidemiology of SE in the paediatric population. diazepam. Sung and Chu. (2001). A comparison of lorazepam.. There was no difference in SMR between idiopathic and cryptogenic SE. There is only one study. Convulsive status epilepticus in infants and children. aggressive treatment may decrease the duration of SE and its associated morbidity and mortality. cultural.A systematic review of the epidemiology of status epilepticus 807 Table 4 Aetiology of SE according to Research Groups Richmond Aetiology Rochester Germany Switzerland North London C (%) A (%) T (%) C (%) A (%) T (%) C (%) A (%) T (%) C (%) A (%) T (%) C (%) A (%) T (%) – 72 25 – 3 – 70 27 – 3 23 46 18 0 13 0 52 20 13 15 8 50 20 8 14 – – – – – – – – – – – 87 63 – 9 – 66 25 – 61 31 – 63 28 35 13 36 – – – – – – – – – – PFC – Acute symptomatic 57 Remote symptomatic 38 Progressive – symptomatic Idiopathic/unknown 5 9 8 9 16 Californian Group excluded because proportional contributions of aetiologies from their study could not be determined. Epilepsia 34:878–883. Aminoff MJ. Aicardi J. Status epilepticus. Simon RP (1980). Yager et al. 1989. Hui et al. Scott R. Only one study has reported on long-term mortality (Logroscino et al. 1988. Epilepsia 11:187– 197. SE is more common in children than adults but most common in the elderly (see Table 3). Quesney LF (1993). 1988. The treatment of convulsive status Ó 2004 EFNS European Journal of Neurology 11. 2003). However. and placebo for the treatment of out-of-hospital status epilepticus. environmental differences and SE. However. Further studies addressing these areas are needed. but not elevated in idiopathic or cryptogenic SE.

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. 2000. and absence/non-convulsive SE. Age groups The age groups in the individual study groups are tabulated in Table 5.. Knake et al. 2002) defined incident cases as cases that were admitted to hospital for the first time with SE in the 7-year study period.. 2003) studies defined incident cases as lifetime first cases of SE.. Risk of epilepsy after febrile convulsions: a national cohort study.. myoclonic. (1998). Coeytaux et al. Wu YW. Ross EM. 2000). In two studies. Outcome of childhood status epilepticus and lengthy febrile convulsions: findings of national cohort study. Hesdorffer et al. 800–810 . Golding J (1993). tonic–clonic. 1998.. 2001).. The Californian (Wu et al. Incident cases were not clearly defined in the other studies. 1998.. The Californian study (Wu et al. Garcia PA.. 1996. 1996.. Status epilepticus in children. Johnston SC (2002). Unprovoked aetiologies were either remote symptomatic or idiopathic/cryptogenic (unknown aetiology) (DeLorenzo et al. Seshia SS (1988). Verity CM. Can J Neurol Sci 15:402–405. was classified as a special class of acute symptomatic SE in the Rochester and North London groups (Hesdorffer et al. 2001). Incident cases The Rochester and North London (Hesdorffer et al. Br Med J 307:225–228. and one had a hemiconvulsive seizure category (Coeytaux et al. Two studies had a separate categorisation for seizures that were diagnosed on EEG findings only (subtle SE) (DeLorenzo et al. Appendix Definitions Aetiology The Californian group’s study listed aetiologies (Wu et al. defined as SE occurring in a febrile illness among children in the absence of another acute symptomatic cause... 2000.A systematic review of the epidemiology of status epilepticus 809 generalised convulsive status epilepticus in man and three experimental models of status epilepticus in the rat. The impact of convulsive status epilepticus on the risk of death varies by age. Knake et al.. Status epilepticus All studies considered SE as a single seizure or series of seizures without recovery of consciousness between seizures lasting at least 30 min. Fitzgerald R. Aetiologies were classified as either provoked (acute symptomatic) or unprovoked.. Towne AR et al. 1996. one had a category for unknown seizure type (Knake et al. Coeytaux et al. 2002) and North London (Chin et al. including CNS infection. Neurology 58:1070–1076.. Golding J (1991). 1996. Br Med J 303:1373– 1376. Chin et al.. 2000). 2001) used a classification system for aetiologies which was similar across research groups. Shek DW. Association with epilepsy Epilepsy was defined in two of the studies and was defined as two or more seizure episodes in a lifetime (DeLorenzo et al. Coeytaux et al. 1996. 2002) while five studies (DeLorenzo et al. Virginia. SE was associated with multiple aetiologies (DeLorenzo et al.. Zhao S. Wang D (2002). All studies divided seizure types initially into partial seizures and generalized seizures.. (1999). 2000). Coeytaux et al. remote symptomatic aetiologies were further classified into those with static CNS lesions and those with progressive CNS lesions (Hesdorffer et al. and partial with secondary generalisation and generalised seizures were divided into tonic. Trevathan E. Epilepsia 40:752–758. Prospective population-based study of intermittent and continuous convulsive status epilepticus in Richmond.. PFC. 1998. A comparison of four treatments for generalized convulsive status epilepticus. Walton NY et al. Neurology 34:244–245. In two studies. Knake et al.... Incidence and mortality of generalized convulsive status epilepticus in California. Hesdorffer et al. SE seizure types The classification of SE type was similar in all studies except the Waterhouse study from the Richmond Group that classified SE into continuous or intermittent. all studies further divided the partial seizure group into simple partial. Treiman DM. Yager JY. Except for the Waterhouse study.):75 (abstract). clonic. 2003) studies exclude non-convulsive SE. 2000). Cheang M.. Coeytaux et al. Garnett LK. Verity CM.. complex partial.. Meyers PD. 1998). 1998. Epilepsia 43 (Suppl. N Engl J Med 339:792–798. Waterhouse EJ. 2001). Table 5 Age groups according to research group Age groups Children Adults Elderly Richmond 31 days to 15 years 16–59 years 60 years and over Rochester Birth to 14 years 15–64 years 65 years and over Germany Excluded 18–59 years 60 years and over Switzerland Birth to 14 years 15–59 years 60 years and over California Birth to 19 years 20–54 years 55 years and over St Louis 31 days to 16 years 17–65 years 65 years and over North London 29 days to 16 years Excluded Excluded Ó 2004 EFNS European Journal of Neurology 11.

. 1996. 2001).810 R. Short-term mortality Three studies defined mortality as the proportion of deaths within 30 days of the cases of incident episode of SE (DeLorenzo et al. Long-term mortality The Rochester group defined long-term mortality as the number of deaths after initial survival for 30 days after intial episode of SE within the population.. Hesdorffer et al.. 2002). F. 2002. Neville and R. B. 1999). The Knake Study defined recurrence as further episodes of SE during the 2-year study period. one study defined it as the proportion of deaths within 60 days of the incident episode (Waterhouse et al. 2000. The Rochester Group did not define recurrence but their retrospective study examined a 20-year period. M.. within 10 years. Chin. Trevathan et al. Ó 2004 EFNS European Journal of Neurology 11. Scott Recurrence of SE The Richmond Group defined recurrence as another episode of SE occurring within a two-year follow-up period following an initial episode of SE. 1998. R. Knake et al. G. C. 800–810 .. and three studies defined it as the proportion of hospital deaths (Coeytaux et al.. Wu et al..