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Purpose: To describe and report initial findings of a system for prospective identification and follow-up of patients with newly diagnosed single unprovoked seizures and epilepsy in Stockholm, Sweden, the Stockholm Incidence Registry of Epilepsy (SIRE).
Methods: From September 2001 through August 2004, a surveillance system has been in use to identify incident cases of first unprovoked seizures (neonatal seizures excluded) and epilepsy among residents of Northern Stockholm, an urban area with approximately 998,500 inhabitants. Potential cases are identified through multiple mechanisms: Network of health care professionals, medical record screening in specific hospital units, including outpatient clinics, emergency room services, and review of requests for electroencephalography (EEG) examination. Potential cases are classified 6 months after the index seizure based on review of medical records.
Results: After screening approximately 10,500 EEG requests and 3,300 medical records, 1,015 persons met the criteria for newly diagnosed unprovoked seizures (430 single seizures; 585 epilepsy). The crude incidence for first unprovoked seizures and epilepsy was 33.9/100,000 person years, (the same adjusted to the European Standard Million), highest the first year of life (77.1/100,000) and in the elderly. No cause could be identified in 62.4%.
Conclusions: We have established a sustainable system for prospective identification of new onset epilepsy cases in Stockholm. Despite a possible under-ascertainment, the registry provides a useful starting point for follow-up studies.
Prospective population-based studies of incident cases are the ideal for an unbiased assessment of the incidence of unprovoked seizures and epilepsy in the population, as well as for exploration of risk factors and assessment of prognosis (ILAE Commission, 1997). However, such studies are uncommon (Keränen et al., 1989; Forsgren, 1990; Sander et al., 1990; Hauser et al., 1993; Sidenwall et al., 1993; Forsgren et al., 1996; Olafsson et al., 1996; Jallon et al., 1997; Annegers et al., 1999; Zarrelli et al., 1999; Jallon et al., 2001; Öun et al., 2003; Forsgren et al., 2005; Olafsson et al., 2005; Christensen et al., 2007). In these studies, incidence rates have ranged from approximately 20 to 80 per 100,000 person years, the variation accounted for by differences in the population at study, ascertainment rate, methodology, and the criteria used (Sander & Shorvon, 1987). To promote conformity in design and thus facilitate comparison, the International League Against Epilepsy (ILAE) has issued guidelines for epidemiological studies on epilepsy (Commission, 1993, 1997). However, with a few exceptions (Olafsson et al., 2005), these recommendations have not been strictly adhered to in previous publications. A limitation of most previous population-based incidence studies of epilepsy is the comparatively small number of included cases. This is important, considering the heterogeneity of epilepsy, and hampers the evaluation of subgroups of, for example, different seizure types, specific etiologies, or age groups.
We set out to establish a system for a prospective identification of all patients with newly diagnosed unprovoked first seizures and epilepsy in Northern Stockholm, Sweden—the Stockholm Incidence Registry of Epilepsy (SIRE). The primary objective was to set up a population-based surveillance system based on data available in medical records that could function over time and thus permit longitudinal epidemiological studies in a large cohort of incident cases. In this first report from the registry, we describe the methodology and the incidence of unprovoked seizures and epilepsy over the first 3 years of SIRE. In the classification of cases, we have applied the ILAE guidelines for epidemiological studies (Commission, 1993; ILAE Commission, 1997) as well as the epilepsy syndrome classification suggested by the ILAE (Commission, 1989).
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The methodology of SIRE was selected to allow for an enduring surveillance of a fairly large population using limited resources and without any interference with the management of the patients. Although the data are derived from multiple sources, they have been assessed in a uniform manner following predefined operational criteria and applying the recommendations of the ILAE. This has allowed us to establish one of the largest population-based incident cohorts of newly diagnosed unprovoked seizures so far.
Analyzing single and recurrent unprovoked seizures together, the crude incidence was 33.9 of 100,000 person years, with the highest incidence in the first year of life and among the elderly. Adding the borderline cases that could not be definitively classified would yield a crude incidence rate of 36.1 of 100,000 person years. This incidence is in the lower range of the incidence rates of 24 to 69 of 100,000 reported from Europe and the U.S. (Joensen, 1986; Keränen et al., 1989; Loiseau et al., 1990; Hauser et al., 1993; Forsgren et al., 1996; Jallon et al., 1997; Olafsson et al., 2005; Christensen et al., 2007). In accordance with most previous population-based studies (Joensen, 1986; Keränen et al., 1989; Hauser et al., 1993; Olafsson et al., 1996; Jallon et al., 1997; Öun et al., 2003; Christensen et al., 2007), the incidence was in general higher among males than females, especially above 60 years of age, while at 1–9 years of age, the highest incidence was observed among girls (Table 1). An underlying presumed etiology was identified in 37.6% of the cases, while only 7.9% were found to have idiopathic epilepsy syndromes.
While our methodology has enabled us to register a large number of incident cases, there are also limitations with the design of SIRE. First, the registry is based entirely on data included in medical records, and their quality set the limit. Additionally, the SIRE does not include a standardized work-up. Availability of EEG or neuroimaging depended on if the patient's physician initiated such investigations. Hence, EEG was performed in 85.2% of the cases and neuroimaging in 83.7%, which is slightly less than in some other studies from Europe (Forsgren,1990; Jallon et al., 2001; Olafsson et al., 2005). Second, the 6 months follow-up limit after the index seizure can affect the classification. In the Rochester study (Hauser et al., 1993), time from a first afebrile seizure to diagnosis exceeded 6 months in 50% of the patients and extended beyond 2 years in more than 30%. Third, the size of the surveyed population and the complexity of the health care involved make it difficult to keep the network of reporting collaborators efficient. It is likely that an under-ascertainment contributes to the comparatively low incidence in our study. Although this is probably rare, patients may seek medical advice for their seizures in regions outside Northern Stockholm. Failure to report a potential case or to identify symptoms as possible seizures could also contribute. It has not been possible to quantify this potential under-ascertainment, but it does not seem to change over time, since the incidence rates were similar over the 3 years under study.
The incidence rates in our study seemed to be lower in all age groups compared to most previous studies (Joensen, 1986; Lavados et al., 1992; Hauser et al., 1993; Sidenvall et al., 1993; Braathen & Theorell, 1995; Forsgren et al., 1996; Olafsson et al., 1996; Jallon et al., 1997; Tekle-Haimanot et al., 1997; Annegers et al., 1999; Jallon et al., 1999; Zarrelli et al., 1999; MacDonald et al., 2000; Freitag et al., 2001; Medina et al., 2005), although this difference was most pronounced among the elderly. However, the distribution among our cases by gender, seizure type, and etiology are in keeping with previous studies, indicating that there is no pronounced selection bias in these respects (Forsgren, 1990; Loiseau et al., 1990; Hauser et al., 1993; Forsgren et al., 1996; Jallon et al., 1997; Annegers et al., 1999; Jallon et al., 1999; Zarrelli et al., 1999; Öun et al., 2003).
Many previous studies have failed to account for detailed operational criteria for the seizure classification, although in general, following the ILAE classification (Kotsopoulos et al., 2002), we found it useful to classify the index seizure based on three levels of information (Table 2). The proportion with unclassified seizures was reduced from 47.4% to 27.8% when all available information was taken into account rather than only the semiology of the index seizure, which demonstrates the importance in describing the basis for seizure classification in studies of this kind. The 27.8% considered to have unclassified seizures is still higher than in most other studies (Sander et al., 1990; Manford et al., 1992; Zarrelli et al., 1999). This can be explained by our dependence on medical records, the short follow-up, and the comparatively low proportion with neuroimaging, but also by our application of strict criteria for classification. With our criteria, onset of generalized seizures was confined to childhood and early adulthood, whereas partial onset, and to a lesser extent unclassified seizures, accounted for all cases from 50 years of age (Fig. 1).
The comparatively low rate of neuroimaging could be expected to affect the reliability of the etiological classification. Nevertheless, the presumed etiologies among our cases were similar to those reported in other population-based studies of epilepsy (Hauser et al., 1993; Olafsson et al., 1996; Jallon et al., 1997, 1999; Olafsson et al., 2005). Stroke was the most common cause followed by brain tumors (Table 3). We found slightly fewer patients with stroke, 11.3% of presumed etiologies to compare with 14%–20% in other studies from the U.S. and Europe (Sander et al., 1990; Forsgren et al., 1996; Olafsson et al., 1996; Zarrelli et al., 1999; Öun et al., 2003), and 2.2% of presumed causes with dementia, to compare with 3.5%–14.8% (Hauser et al., 1993; Forsgren et al., 1996; Jallon et al., 1997; Olafsson et al., 2005). A higher proportion with dementia and stroke could be expected with a more efficient case ascertainment among the elderly, but our strict criteria for presumed etiology versus risk factors could also contribute.
In conclusion, we have established a surveillance system to identify patients with newly diagnosed unprovoked seizures and epilepsy in Stockholm. Our methods are probably associated with an under-ascertainment of cases, in particular among the elderly. Apart from that, we have no indications of selection bias as the distribution of cases by gender, seizure type, and etiology is comparable to other population-based studies. The large number of newly diagnosed patients with unprovoked seizures and epilepsy in SIRE appears to be suitable for further studies exploring in more detail comorbidities and risk factors as well as long-term follow-up of prognosis utilizing the unique patient identification number that is used in all medical records and public registries in the country.