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Validation of epilepsy diagnoses in the Danish National Hospital Register
Epilepsy Research (2007) 75, 162—170
journal homepage: www.elsevier.com/locate/epilepsyres
Validation of epilepsy diagnoses in the Danish National Hospital Register Jakob Christensen a,b,∗, Mogens Vestergaard c,d, Jørn Olsen c,e, Per Sidenius b a
Department of Neurology, Aarhus University Hospital, Aarhus, Denmark Department of Clinical Pharmacology, University of Aarhus, Denmark c Department of Epidemiology, Institute of Public Health, University of Aarhus, Denmark d Department of General Medicine, Institute of Public Health, University of Aarhus, Denmark e Department of Epidemiology, School of Public Health, UCLA, Los Angeles, CA, USA b
Received 30 August 2006; received in revised form 20 March 2007; accepted 18 May 2007
KEYWORDS Epilepsy; Health registries; Classification; Validation; ICD-8; ICD-10
Summary Purpose: To validate the diagnosis of epilepsy in the Danish National Hospital Register. Methods: We randomly selected 200 patients registered with epilepsy in the Danish National Hospital Register between 1977 and 2002 and validated the diagnosis according to the guidelines developed by the International League Against Epilepsy. Results: We reviewed the medical records of 188 (94%) persons from 57 departments at 41 hospitals. The epilepsy diagnoses were confirmed in 153 patients, providing a positive predictive value for epilepsy of 81% (95% confidence interval (95% CI): 75—87%). Among the 35 patients who did not fulfill the criteria for epilepsy, 14 were admitted after a single, unprovoked seizure. Among patients registered with epilepsy the positive predictive value of seizure disorder was 89% (95% CI: 83—93%). Among patients classified with epilepsy syndromes, the positive predictive value for syndrome classification was 60% (95% CI: 44—74%) for epilepsy with complex focal seizures and 35% (95% CI: 22—51%) for primary generalized epilepsy. Conclusion: The validity of the epilepsy diagnoses in the Danish National Hospital Register has a moderate to high positive predictive value for epilepsy, but a relatively low predictive value for epilepsy syndromes. © 2007 Elsevier B.V. All rights reserved.
Introduction Population-based registries ∗
Corresponding author at: Department of Neurology, Aarhus University Hospital, Norrebrogade 44, DK-8000 Aarhus C, Denmark. Tel.: +45 8949 3333; fax: +45 8949 3300. E-mail address: [email protected] (J. Christensen).
Population-based health registries have provided valuable insight into the epidemiology of epilepsy (Hauser et al., 1993; Jallon et al., 1999; Annegers et al., 1984), although
0920-1211/$ — see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.eplepsyres.2007.05.009
Validation of epilepsy diagnoses in the Danish National Hospital Register population-based registries are rarely developed or designed for research purposes (Christensen et al., 2005a; Kwan and Brodie, 2000). The use of these registries in research often requires information about the clinical criteria used for registering people with epilepsy (Sorensen et al., 1996).
Epidemiological studies of seizures In 1993, the International League Against Epilepsy (ILAE) proposed epidemiologic guidelines in which an epileptic seizure was defined as ‘‘a clinical manifestation presumed to result from an abnormal and excessive discharge of a set of neurons in the brain. The clinical manifestation consists of sudden and transitory abnormal phenomena, which may include alteration of consciousness, motor, sensory, autonomic or psychic events, perceived by the patient or an observer’’ (Commission, ILAE, 1993). For epidemiological purposes it was recommended that an effort should be made to classify seizure type based predominantly on clinical criteria (Commission, ILAE, 1993).
Epidemiological studies of epilepsy An epilepsy diagnosis was defined as ‘‘A condition characterized by recurrent (two or more) epileptic seizures, unprovoked by any immediate identified cause. Multiple seizures occurring in a 24-h period are considered a single event. An episode of status epilepticus is considered a single event. Individuals who have had only febrile seizures or only neonatal seizures as herein defined are excluded from this category’’ (Commission, ILAE, 1993). The use of the ILAE Classification of epilepsy syndrome was encouraged, however, it was acknowledged that in many settings a proper classification of epileptic syndromes could not always be obtained (Commission, ILAE, 1993).
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Methods Danish Civil Registration System We used data from the Danish Civil Registration System (Pedersen et al., 2006) to identify all persons born in Denmark and alive and resident in Denmark from 1 January 1977 to 31 December 2002 (N = 6,543,341 persons). All live-born children with a permanent address in Denmark are assigned a unique personal identification number (CPR number), which is stored in the Danish Civil Registration System together with information on vital status, emigration, and place of living. The CPR number is used as the key to link information from all national registers at the individual level.
The Danish National Hospital Register The Danish National Hospital Register (Andersen et al., 1999) contains information on all discharges from Danish hospitals since 1977 and on all outpatients since 1995. Diagnostic information in the Danish National Hospital Register is based on the Danish version of the International Classification of Diseases 8th revision (ICD-8) from 1977 to 1993 (Sundhedsstyrelsen, 1976; World Health Organization, 1967), and the International Classification of Diseases 10th revision (ICD-10) from 1994 and onward (World Health Organization, 1994). In Denmark, all hospital and outpatient treatment is tax paid and free of charge for patients, including those at the only private epilepsy center (Dianalund Epilepsy Center). This center is included in the hospital register we use. Patients are registered at each admission or outpatient contact, and some patients may therefore have more than one diagnosis, but only information relating to the first admission/contact was evaluated. Outpatient visits to private practice and general practitioners are not included in the register.
The epilepsy diagnosis in the Danish National Hospital Register
The ILAE criteria for seizures (Commission, ILAE, 1981), and epilepsies and epileptic syndromes (Commission, ILAE, 1989) have been used in epidemiological studies on epilepsy (Christensen et al., 2005a). However, the ILAE terminology and classification have not been unequivocally used in population-based registries, such as the ones based on the WHO’s ICD. Limited evidence indicates that epilepsy classification based on ICD varies greatly compared with ILAE criteria, and that correspondence between the two classifications depends on factors such as number of hospital admissions and use of antiepileptic drugs (Ehrenstein et al., 2006; Holden et al., 2005a, b; Tomson and Forsgren, 2003).
We included all people registered with at least one epilepsy diagnosis (ICD-8: 345; ICD-10: G40—G41). About 40—50% of incident cases with status epilepticus have a previous diagnosis of epilepsy (Vignatelli et al., 2003; Knake et al., 2001; Coeytaux et al., 2000), and we therefore included status epilepticus (345.29) from the ICD8 period, and status epilepticus (G41) from the ICD-10 period in our dataset. Epilepsy diagnoses in ICD in general and ICD-10 in particular are based on a mixture of seizures and syndromes, and there is no exact correspondence between them and the epilepsy syndrome and seizure classification defined by ILAE (Commission, ILAE, 1981, 1989) (Table 1). However, we specifically looked at epilepsy with complex focal seizures (ICD-8: 345.31; ICD-10: G40.2) and primary generalized epilepsy (ICD-8: 345.09, 345.10, 345.11; ICD-10: G40.3) (Table 1) because the correspondence between the classifications in ILAE and in ICD-8 and ICD-10 are most clear-cut for these diagnoses. If a patient was given both an unspecified epilepsy code and a syndrome code at their first registration in the Danish National Hospital Register, we used the syndrome code for validation. Patients given two different syndrome codes were considered to have undetermined epilepsy.
Aim of the study
Assessment of the epilepsy diagnosis and syndrome
Our aim was to validate epilepsy diagnoses according to ILAE criteria from hospital admissions and outpatient contacts in the Danish National Hospital Register based on WHO’s ICD, taking epilepsy syndrome into account.
Patients were stratified into those born before and those born after 1977, i.e. after the Danish National Hospital Register was established. From each of these two groups we randomly selected 50 patients to evaluate whether the validity of the epilepsy diagnosis changed over time. In addition, we randomly selected 50 patients
ILAE classification versus the WHO International Classification of Disease (ICD)
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Table 1 International classification of epilepsies and epileptic syndromes as defined by ILAE vs. the two versions of WHO’s International Classification of Disease (ICD8/ICD-10) used in the Danish National Hospital Register Focal epilepsies and syndromes ICD-8
International classification of epilepsies and epileptic syndromes Idiopathic with age-related onset
Benign childhood epilepsy with centro temporal spike
345.30 (4.8%)
Epilepsia focalis
G40.0 (3.1%)
Focal idiopathic epilepsy and epileptic syndromes with seizures of focal onset
Childhood epilepsy with occipital paroxysms Primary reading epilepsy
345.31 (7.1%)
Epilepsia psychomotorica Convulsiones focales aliae definitae Convulsiones focales
Chronic progressive epilepsia partialis continua of childhood
G40.1 (4.2%)
Syndromes characterized by seizures with specific modes of precipitation
G40.2 (10.2%)
Focal symptomatic epilepsy and epileptic syndromes with simple focal seizures Focal symptomatic epilepsy and epileptic syndromes with complex focal seizures
345.38 (0.3%)
345.39 (0.9%) Symptomatic
ICD-10
Temporal lobe epilepsies Frontal lobe epilepsies Parietal lobe epilepsies Occipital lobe epilepsies Cryptogenic
Same as above
J. Christensen et al.
Generalized epilepsies and syndromes ICD-8
International classification of epilepsies and epileptic syndromes Idiopathic, with age-related onset
Cryptogenic or symptomatic
ICD-10
Benign neonatal familial convulsions
345.09 (3.2%)
Epilepsia petit mal
Benign neonatal convulsions
345.10 (27.0%)
Epilepsia grand mal
Benign myoclonic epilepsy in infancy Childhood absence epilepsy Juvenile absence epilepsy Juvenile myoclonic epilepsy Epilepsy with grand mal seizures on awakening Other generalized idiopathic epilepsies not defined above Epilepsies with seizures precipitated by specific modes of activation West syndrome
345.11 (1.6%)
Lennox-Gastaut syndrome
345.18 (1.6%)
Epilepsia myoclonica infantilis Convulsiones universales aliae definitae
G40.3 (4.9%)
Generalized idiopathic epilepsy and epileptic syndromes
G40.4 (1.9%)
Other generalized epilepsy and epileptic syndromes
Validation of epilepsy diagnoses in the Danish National Hospital Register
Table 1 (Continued )
Epilepsy with myoclonic-astatic seizures Epilepsy with myoclonic absences Symptomatic
Nonspecific etiology Early myoclonic encephalopathy Early infantile epileptic encephalopathy with suppression burst Other symptomatic generalized epilepsies not defined above Specific syndromes Diseases in which seizures are a presenting or prominent feature
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166
Table 1 (Continued ) Epilepsies and syndromes undetermined as to whether they are focal or generalized International classification of epilepsies and epileptic syndromes With both generalized and focal seizures
ICD-8
ICD-10
90.9a
Neonatal seizures
G40.5 (1.8%)
Special epileptic syndromes
Epilepsy with continuous spike-waves during slow wave sleep
G40.6 (8.5%)
Acquired epileptic aphasia (Landau-Kleffner syndrome)
G40.7 (1.4%)
Grand mal seizures, unspecified (with or without petit mal) Petit mal, unspecified (without grand mal seizures)
Neonatal seizures
345.99 (45.4%)
Severe myoclonic epilepsy in infancy
345.19 (6.9%)
Epilepsia alia et non specificata Convulsiones universales
Other undetermined epilepsies not defined above Without unequivocal generalized or focal features. All Without unequivocal generalized cases with generalized or focal features. All cases with or focal features generalized tonic clonic seizures where clinical and EEG findings do not permit classification as clearly generalized of localization-related Special syndromes, and provoked and single seizures
40.9 (56.0%)
ICD-8
International classification of epilepsies and epileptic syndromes Situation-related seizures
G40.8 (6.4%)
780.20a
Isolated seizures or isolated status epilepticus Seizures occurring only when there is an acute metabolic or toxic event due to factors such as alcohol, drugs, eclampsia, nonketotic hyperglycemia
780.21a 780.29a
ICD-10
Convulsiones e furore Convulsiones febriles Convulsiones
R56.0a
Convulsiones febriles
R56.8a
Convulsions, others and unspecified
J. Christensen et al.
Febrile convulsions
Other epilepsy not specified whether partial or generalized type Epilepsy, unspecified
G41.8 (0.1%) G41.9 (0.7%)
G41.2 (0.1%)
We identified 90,994 epilepsy diagnoses among 88,781 persons; 2171 (2.5%) persons had two or more epilepsy diagnoses on the first admission with epilepsy. There were 49,521 epilepsy diagnoses among 48,667 persons based on ICD-8, and 41,473 epilepsy diagnoses among 40,167 persons based on ICD-10. There were 53 persons registered with both an ICD-8 and an ICD-10 diagnosis. For each of the diagnoses we calculated the proportion of diagnoses used (in %) for ICD-8 and ICD-10 separately. a These ICD-8/ICD-10 codes were not included as epilepsy.
345.29 (1.2%) Status epilepticus
G41.1 (0.1%)
G41.0 (0.8%)
ICD-8 International classification of epilepsies and epileptic syndromes
Status epilepticus
Table 1 (Continued )
Status epilepticus
ICD-10
Generalized tonic/clonic status epilepticus (grand mal) Non-convulsive status epilepticus absence type (petit mal) Non-convulsive status epilepticus complex—partial type Status epilepticus, other type Status epilepticus, unspecified
Validation of epilepsy diagnoses in the Danish National Hospital Register
167
from each group of patients with a first diagnosis of epilepsy with complex focal seizures and patients with a first diagnosis of primary generalized epilepsy. Thus, we obtained a total sample of 200 patients with an epilepsy diagnosis in the Danish National Hospital Register. The number of cases evaluated (200) was set by time and financial constrains. This study was approved by the Danish Data Protection Agency, the Danish National Board of Health, and the head of the clinical departments. The medical records were retrieved from hospitals all over Denmark. The following information was extracted from the medical records: age, gender, date of first seizure, date of first registration in the Danish National Hospital Register, seizure type, EEG findings, and CT/MRI findings. One of the authors (P.S.), who is a consultant in adult neurology and trained in diagnosing and treating patients with epilepsy, classified the patients according to ILAE criteria (Commission, ILAE, 1981, 1989, 1993) into: (1) epilepsy or (2) not epilepsy. Epilepsy diagnoses were categorized into: (a) definite epilepsy or (b) probable epilepsy, and patients were given the latter label if the information from medical records on history of epilepsy and use of antiepileptic drugs made it likely that the patient had epilepsy, but information was missing needed to make a definite diagnosis (e.g. seizure presentation or EEG findings). Subsequently, the epilepsies were classified into the following syndrome categories: (a) focal epilepsy with simple focal seizures, with and without secondarily generalized seizures; (b) focal epilepsy with complex focal seizures, with and without secondarily generalized seizures; (c) primary generalized epilepsy; (d) unclassifiable epilepsy. The physician (P.S.) was blinded with regard to the specific epilepsy syndrome registered in the Danish National Hospital Register.
Results Validation process Medical records were collected from 57 departments at 41 hospitals. Medical records were missing for 12 (6%) patients. In the remaining 188 medical records, we found information on neuroimaging in 90 (48%) patients (MRI in 25 (28%) of patients and CT in 65 (72%) of patients) and EEG in 150 (80%) patients.
Epilepsy diagnosis Overall, the epilepsy diagnosis was confirmed in 153 patients (definite epilepsy, n = 131, probable epilepsy, n = 22), corresponding to a positive predictive value of 81% (95% CI: 75—87%) (the probability of a patient having epilepsy given this patient is registered with a diagnosis of epilepsy). We calculated a positive predictive value for epilepsy assuming that all 12 patients with missing information did not have epilepsy. This ‘‘worst case scenario’’ gave a positive predictive value for epilepsy of 77% (95% CI: 70—82%). The positive predictive value of an epilepsy diagnosis was 84% (95% CI: 75—91%) among the 83 patients diagnosed according to ICD-8 (1977—1993), and 79% (95% CI: 70—86%) among the 105 patients diagnosed according to ICD10 (1994—2002). Among 150 persons diagnosed with epilepsy at a specialized department (pediatrics, neurosurgery, and neurology), 125 had a diagnosis of definite or probable epilepsy, corresponding to a positive predictive value of 83% (95% CI: 76—89%). Among 180 medical records with valid
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J. Christensen et al.
Table 2 Agreement between a validated epilepsy diagnosis based upon ILAE criteria and a register diagnosis in the Danish National Hospital Registry using WHO’s International Classification of Disease (ICD-8/ICD-10) Validated diagnosis according to ILAE criteria (epilepsy syndrome)
Register diagnosis in the Danish National Hospital Register (based on WHO’s ICD-8/ICD-10) All epilepsy diagnoses (N (%))a
Epilepsy syndrome diagnoses (N (%)) Epilepsy with complex focal seizuresb
Primary generalized epilepsyc
Total (N (%))
Focal epilepsy (simple partial) Focal epilepsy (complex partial) Primary generalized epilepsy Not classifiable epilepsy
15 (15) 23 (23) 11 (11) 24 (24)
5 (10) 28 (56) 5 (10) 5 (10)
3 (6) 5 (10) 17 (34) 12 (24)
Not epilepsy Single seizure Other
10 (10) 10 (10)
0 (0) 4 (8)
4 (8) 7 (14)
14 (7) 21 (10.5)
7 (7)
3 (6)
2 (4)
12 (6)
100 (100)
50 (100)
50 (100)
200 (100)
Missing information Total
23 55 33 41
(11.5) (27.5) (16.5) (20.5)
In a total sample of 200 patients registered with an epilepsy diagnosis, 100 were sampled from the entire population registered with epilepsy, 50 were sampled from the population with a syndrome diagnosis of epilepsy with focal seizures and 50 were sampled among patients with a syndrome diagnosis of primary generalized epilepsy. a Epilepsy—–ICD-8: 345; ICD-10: G40—G41. b Epilepsy with complex focal seizures—–ICD-8: 345.31; ICD-10: G40.2. c Primary generalized epilepsy—–ICD-8: 345.09, 345.10, 345.11; ICD-10: G40.3.
information on time of first seizure, 64% were registered in the Danish National Hospital Register within a year after the first seizure, and 90% were registered within 5 years.
Seizure diagnosis Among the 35 patients who did not meet the epilepsy criteria, the reason for 14 patients was that only one unprovoked seizure episode was reported. Thus, 167 out of 188 patients registered with epilepsy had a seizure disorder corresponding to a positive predictive value for seizure disorder of 89% (95% CI: 83—93%). Assuming that all patients with missing records (n = 12) did not have an unprovoked seizure episode, we calculated a positive predictive value for seizure disorder. This ‘‘worst case scenario’’ gave a positive predictive value for seizure disorder of 84% (95% CI: 78—88%). Diagnoses in the remaining patients who did not fulfill the epilepsy diagnosis were: observation for epilepsy (but diagnosis not confirmed) (n = 6), syncope (n = 3), headache (cephalagia) (n = 2), myoclonia (n = 2), bradycardia/respiratory problems (n = 2), behavioral problems (n = 2), febrile seizure (n = 1), psychogenic seizures (n = 1), dyskinesias (n = 1), and mental retardation (n = 1). Among the six patients, who were considered ‘‘under observation for epilepsy’’, none had acute symptomatic seizures.
Epilepsy syndrome Among patients diagnosed with complex focal epilepsy in the Danish National Hospital Register, we found that 28 of 47 fulfilled the ILAE criteria for complex focal epilepsy (positive predictive value 60%; 95% CI: 44—74%) (Tables 1 and 2).
Among patients diagnosed with primary generalized epilepsy in the Danish National Hospital Register, we found that 17 of 48 fulfilled the ILAE diagnostic criteria for primary generalized epilepsy (positive predictive value 35%; 95% CI: 22—51%) (Tables 1 and 2).
Discussion Validity of the epilepsy diagnosis We found that 81% of persons registered with epilepsy in the Danish National Hospital Register fulfilled the ILAE criteria for an epilepsy diagnosis. Although care should be taken when extending these finding to other populations, the results are quite similar to what was found in a hospital-based register in Stockholm, Sweden covering the years 1980—1989 (Tomson, 2000). Among 171 patients admitted for inpatient care with a diagnosis of epilepsy, the epilepsy diagnosis was found to be correct in 79% of the cases (Tomson, 2000). A recent paper from North Jutland County, Denmark compared the physician-recorded diagnosis with the hospital discharge diagnosis in 69 children hospitalized with epilepsy between 1998 and 2000 (Ehrenstein et al., 2006). They found a positive predictive value of 75% for epilepsy (Ehrenstein et al., 2006). Data from epilepsy patients enrolled in the Lovelace Health Plan in Albuquerque, New Mexico between 1996 and 1998 showed that corroboration of an epilepsy diagnosis varied according to the number of diagnostic entries: 38.8% (1 entry), 69.2% (2—3 entries) and 100.0% (≥4 entries) (Holden et al., 2005a,b). The authors combined data from various sources to develop an algorithm based on the ICD-9 diagnosis of
Validation of epilepsy diagnoses in the Danish National Hospital Register epilepsy, the use of diagnostic procedures (e.g. neuroimaging and EEG), and use of antiepileptic drugs. The model with the best prediction of epilepsy used ICD-9 diagnoses of epilepsy and antiepileptic drugs as predictors for epilepsy (positive predictive value 84%)(Holden et al., 2005a,b). Our study was based on the first diagnosis of epilepsy, and we could probably have increased the predictive value significantly by restricting the cohort to patients with ≥4 entries. However, most epidemiological studies are likely to use the first diagnosis to avoid survival bias or a restriction to the most severe cases (Christensen et al., 2005b; Vestergaard et al., 2007).
Validity of a seizure diagnosis We excluded patients with single seizures according to current guidelines for epidemiologic studies on epilepsy (Commission, ILAE, 1993). We therefore excluded patients who may have been considered epilepsy patients in clinical practice (e.g. patients with specific syndromes defined by certain EEG patterns or epilepsy associated with intracranial tumors). Although not all patients would later fulfill the diagnostic criteria for epilepsy (Annegers, 2004), our findings most likely underestimated the ‘‘true’’ predictive value of the epilepsy diagnosis. Other population-based studies in epilepsy have included patients with single seizure episodes and patients with acute symptomatic seizures (Annegers et al., 1999; Cockerell et al., 1997; Forsgren et al., 1996; Jallon et al., 1999). Broadening the epilepsy definition beyond the ILAE definitions to include seizure disorders in general increased the predictive value of an epilepsy diagnosis to 89% in the present study, identical to findings from an assessment in 69 children reporting a positive predictive value for seizures of up to 89% (Ehrenstein et al., 2006).
Validity of the syndrome diagnosis We found a low predictive value when we focused on the ICD diagnosis of complex focal epilepsy and primary generalized epilepsy. One reason may be that the diagnosis of epilepsy is essentially clinical (Commission, ILAE, 1989), and despite high-quality diagnostic procedures (e.g. video-EEG), diagnostic certainty is not always possible. Another reason for the low predictive value is provided by comparing the terminology and classification of epilepsy syndromes as defined by ILAE with the classification and the terminology used in WHO’s ICD-8/ICD-10, which shows that there are major differences (Table 1). Accordingly, the proportion of patients classified with each of the ICD codes seems to vary a great deal between ICD-8 and ICD10—–not least for codes for primary generalized epilepsy (Table 1). Hopefully, future versions of ICD and ILAE guidelines will be more comparable (Annegers, 2004; Wolf, 2003). The ICD has undergone several changes and has been used to varying degrees over time. The IDC-9, for example, has never been implemented in Denmark. However, we did not identify important difference in the predictive value of an epilepsy diagnosis from ICD-8 to ICD-10.
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Completeness of the epilepsy diagnosis in the Danish National Hospital Register In this study, we did not assess the completeness of the epilepsy diagnosis in the Danish National Hospital Register. Extending the diagnoses to include codes for convulsions would probably increase the completeness, but lower the predictive value (Annegers, 2004; Holden et al., 2005a). We believe severe cases of epilepsy are most likely hospitalized and the Danish National Hospital Register includes also outpatients and therefore less severely affected cases of the epilepsy population compared with other hospitalised based registers (Tomson and Forsgren, 2003). Furthermore, most patients with epilepsy will probably come in contact with the hospital system at some point in time and thereby be included in the register since the register includes all diagnoses, not only the cause for hospitalization (the register allows for up to 20 diagnoses per admission or contact). Furthermore, patients referred for diagnostic procedures (e.g. EEG or MRI) will be included if they have epilepsy when examined. This is supported by the finding that 64% of patients with epilepsy were included in the register 1 year after the first seizure. The register includes patients from both specialized and non-specialized departments, probably adding to a more complete registration of cases similar to other population-based studies (Annegers et al., 1999; Cockerell et al., 1997; Forsgren et al., 1996; Jallon et al., 1999). The Danish National Hospital Register allows tracing persons over several decades owing to the unique identification in the Danish Civil Registration System, thereby ensuring a minimal loss at follow-up and preventing selection bias. In addition, the large population included in the Danish National Hospital Register provides a possibility to study rare events and is therefore a valuable data source for studying causes and consequences of epilepsy. Although ad hoc research studies using primary data will be able to get better diagnostic data and will be able to identify people who qualify for the diagnoses but never reach the hospital, these studies may be subject to sources of bias that do not compensate for better diagnostic data. Most ad hoc studies have low response rates, and long-term follow-up is very difficult to achieve for all. Furthermore, large-scale ad hoc studies are very expensive. Use of registers may offer a cheaper and at times even a methodologically superior alternative.
Acknowledgements We are indebted to Birgitte Jensen Hanner for enduring the hard work of collecting and systematizing information from the medical records. The study could not have been performed without help from the hospital secretarial staff at the involved departments. We would like to thank Carsten Bødker Pedersen and Marianne Gørtz Pedersen for help with the retrieval of epilepsy cases from the Danish National Hospital Register and with the calculation of proportion patients registered with the individual epilepsy codes. The study was supported by the Danish Research Agency (grant no.: 22-02-0207), P.A. Messerschmidt and Wife’s Foundation, Managing Director Kurt Bønnelycke and Mrs. Grethe Bønnelyckes Foundation, Research Initiative of Aarhus Uni-
170 versity Hospital, and Aase and Ejnar Danielsen’s Foundation. The Danish National Research Foundation funds the activities of the Danish Epidemiology Science Center.
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journal homepage: www.elsevier.com/locate/epilepsyres
Validation of epilepsy diagnoses in the Danish National Hospital Register Jakob Christensen a,b,∗, Mogens Vestergaard c,d, Jørn Olsen c,e, Per Sidenius b a
Department of Neurology, Aarhus University Hospital, Aarhus, Denmark Department of Clinical Pharmacology, University of Aarhus, Denmark c Department of Epidemiology, Institute of Public Health, University of Aarhus, Denmark d Department of General Medicine, Institute of Public Health, University of Aarhus, Denmark e Department of Epidemiology, School of Public Health, UCLA, Los Angeles, CA, USA b
Received 30 August 2006; received in revised form 20 March 2007; accepted 18 May 2007
KEYWORDS Epilepsy; Health registries; Classification; Validation; ICD-8; ICD-10
Summary Purpose: To validate the diagnosis of epilepsy in the Danish National Hospital Register. Methods: We randomly selected 200 patients registered with epilepsy in the Danish National Hospital Register between 1977 and 2002 and validated the diagnosis according to the guidelines developed by the International League Against Epilepsy. Results: We reviewed the medical records of 188 (94%) persons from 57 departments at 41 hospitals. The epilepsy diagnoses were confirmed in 153 patients, providing a positive predictive value for epilepsy of 81% (95% confidence interval (95% CI): 75—87%). Among the 35 patients who did not fulfill the criteria for epilepsy, 14 were admitted after a single, unprovoked seizure. Among patients registered with epilepsy the positive predictive value of seizure disorder was 89% (95% CI: 83—93%). Among patients classified with epilepsy syndromes, the positive predictive value for syndrome classification was 60% (95% CI: 44—74%) for epilepsy with complex focal seizures and 35% (95% CI: 22—51%) for primary generalized epilepsy. Conclusion: The validity of the epilepsy diagnoses in the Danish National Hospital Register has a moderate to high positive predictive value for epilepsy, but a relatively low predictive value for epilepsy syndromes. © 2007 Elsevier B.V. All rights reserved.
Introduction Population-based registries ∗
Corresponding author at: Department of Neurology, Aarhus University Hospital, Norrebrogade 44, DK-8000 Aarhus C, Denmark. Tel.: +45 8949 3333; fax: +45 8949 3300. E-mail address: [email protected] (J. Christensen).
Population-based health registries have provided valuable insight into the epidemiology of epilepsy (Hauser et al., 1993; Jallon et al., 1999; Annegers et al., 1984), although
0920-1211/$ — see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.eplepsyres.2007.05.009
Validation of epilepsy diagnoses in the Danish National Hospital Register population-based registries are rarely developed or designed for research purposes (Christensen et al., 2005a; Kwan and Brodie, 2000). The use of these registries in research often requires information about the clinical criteria used for registering people with epilepsy (Sorensen et al., 1996).
Epidemiological studies of seizures In 1993, the International League Against Epilepsy (ILAE) proposed epidemiologic guidelines in which an epileptic seizure was defined as ‘‘a clinical manifestation presumed to result from an abnormal and excessive discharge of a set of neurons in the brain. The clinical manifestation consists of sudden and transitory abnormal phenomena, which may include alteration of consciousness, motor, sensory, autonomic or psychic events, perceived by the patient or an observer’’ (Commission, ILAE, 1993). For epidemiological purposes it was recommended that an effort should be made to classify seizure type based predominantly on clinical criteria (Commission, ILAE, 1993).
Epidemiological studies of epilepsy An epilepsy diagnosis was defined as ‘‘A condition characterized by recurrent (two or more) epileptic seizures, unprovoked by any immediate identified cause. Multiple seizures occurring in a 24-h period are considered a single event. An episode of status epilepticus is considered a single event. Individuals who have had only febrile seizures or only neonatal seizures as herein defined are excluded from this category’’ (Commission, ILAE, 1993). The use of the ILAE Classification of epilepsy syndrome was encouraged, however, it was acknowledged that in many settings a proper classification of epileptic syndromes could not always be obtained (Commission, ILAE, 1993).
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Methods Danish Civil Registration System We used data from the Danish Civil Registration System (Pedersen et al., 2006) to identify all persons born in Denmark and alive and resident in Denmark from 1 January 1977 to 31 December 2002 (N = 6,543,341 persons). All live-born children with a permanent address in Denmark are assigned a unique personal identification number (CPR number), which is stored in the Danish Civil Registration System together with information on vital status, emigration, and place of living. The CPR number is used as the key to link information from all national registers at the individual level.
The Danish National Hospital Register The Danish National Hospital Register (Andersen et al., 1999) contains information on all discharges from Danish hospitals since 1977 and on all outpatients since 1995. Diagnostic information in the Danish National Hospital Register is based on the Danish version of the International Classification of Diseases 8th revision (ICD-8) from 1977 to 1993 (Sundhedsstyrelsen, 1976; World Health Organization, 1967), and the International Classification of Diseases 10th revision (ICD-10) from 1994 and onward (World Health Organization, 1994). In Denmark, all hospital and outpatient treatment is tax paid and free of charge for patients, including those at the only private epilepsy center (Dianalund Epilepsy Center). This center is included in the hospital register we use. Patients are registered at each admission or outpatient contact, and some patients may therefore have more than one diagnosis, but only information relating to the first admission/contact was evaluated. Outpatient visits to private practice and general practitioners are not included in the register.
The epilepsy diagnosis in the Danish National Hospital Register
The ILAE criteria for seizures (Commission, ILAE, 1981), and epilepsies and epileptic syndromes (Commission, ILAE, 1989) have been used in epidemiological studies on epilepsy (Christensen et al., 2005a). However, the ILAE terminology and classification have not been unequivocally used in population-based registries, such as the ones based on the WHO’s ICD. Limited evidence indicates that epilepsy classification based on ICD varies greatly compared with ILAE criteria, and that correspondence between the two classifications depends on factors such as number of hospital admissions and use of antiepileptic drugs (Ehrenstein et al., 2006; Holden et al., 2005a, b; Tomson and Forsgren, 2003).
We included all people registered with at least one epilepsy diagnosis (ICD-8: 345; ICD-10: G40—G41). About 40—50% of incident cases with status epilepticus have a previous diagnosis of epilepsy (Vignatelli et al., 2003; Knake et al., 2001; Coeytaux et al., 2000), and we therefore included status epilepticus (345.29) from the ICD8 period, and status epilepticus (G41) from the ICD-10 period in our dataset. Epilepsy diagnoses in ICD in general and ICD-10 in particular are based on a mixture of seizures and syndromes, and there is no exact correspondence between them and the epilepsy syndrome and seizure classification defined by ILAE (Commission, ILAE, 1981, 1989) (Table 1). However, we specifically looked at epilepsy with complex focal seizures (ICD-8: 345.31; ICD-10: G40.2) and primary generalized epilepsy (ICD-8: 345.09, 345.10, 345.11; ICD-10: G40.3) (Table 1) because the correspondence between the classifications in ILAE and in ICD-8 and ICD-10 are most clear-cut for these diagnoses. If a patient was given both an unspecified epilepsy code and a syndrome code at their first registration in the Danish National Hospital Register, we used the syndrome code for validation. Patients given two different syndrome codes were considered to have undetermined epilepsy.
Aim of the study
Assessment of the epilepsy diagnosis and syndrome
Our aim was to validate epilepsy diagnoses according to ILAE criteria from hospital admissions and outpatient contacts in the Danish National Hospital Register based on WHO’s ICD, taking epilepsy syndrome into account.
Patients were stratified into those born before and those born after 1977, i.e. after the Danish National Hospital Register was established. From each of these two groups we randomly selected 50 patients to evaluate whether the validity of the epilepsy diagnosis changed over time. In addition, we randomly selected 50 patients
ILAE classification versus the WHO International Classification of Disease (ICD)
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Table 1 International classification of epilepsies and epileptic syndromes as defined by ILAE vs. the two versions of WHO’s International Classification of Disease (ICD8/ICD-10) used in the Danish National Hospital Register Focal epilepsies and syndromes ICD-8
International classification of epilepsies and epileptic syndromes Idiopathic with age-related onset
Benign childhood epilepsy with centro temporal spike
345.30 (4.8%)
Epilepsia focalis
G40.0 (3.1%)
Focal idiopathic epilepsy and epileptic syndromes with seizures of focal onset
Childhood epilepsy with occipital paroxysms Primary reading epilepsy
345.31 (7.1%)
Epilepsia psychomotorica Convulsiones focales aliae definitae Convulsiones focales
Chronic progressive epilepsia partialis continua of childhood
G40.1 (4.2%)
Syndromes characterized by seizures with specific modes of precipitation
G40.2 (10.2%)
Focal symptomatic epilepsy and epileptic syndromes with simple focal seizures Focal symptomatic epilepsy and epileptic syndromes with complex focal seizures
345.38 (0.3%)
345.39 (0.9%) Symptomatic
ICD-10
Temporal lobe epilepsies Frontal lobe epilepsies Parietal lobe epilepsies Occipital lobe epilepsies Cryptogenic
Same as above
J. Christensen et al.
Generalized epilepsies and syndromes ICD-8
International classification of epilepsies and epileptic syndromes Idiopathic, with age-related onset
Cryptogenic or symptomatic
ICD-10
Benign neonatal familial convulsions
345.09 (3.2%)
Epilepsia petit mal
Benign neonatal convulsions
345.10 (27.0%)
Epilepsia grand mal
Benign myoclonic epilepsy in infancy Childhood absence epilepsy Juvenile absence epilepsy Juvenile myoclonic epilepsy Epilepsy with grand mal seizures on awakening Other generalized idiopathic epilepsies not defined above Epilepsies with seizures precipitated by specific modes of activation West syndrome
345.11 (1.6%)
Lennox-Gastaut syndrome
345.18 (1.6%)
Epilepsia myoclonica infantilis Convulsiones universales aliae definitae
G40.3 (4.9%)
Generalized idiopathic epilepsy and epileptic syndromes
G40.4 (1.9%)
Other generalized epilepsy and epileptic syndromes
Validation of epilepsy diagnoses in the Danish National Hospital Register
Table 1 (Continued )
Epilepsy with myoclonic-astatic seizures Epilepsy with myoclonic absences Symptomatic
Nonspecific etiology Early myoclonic encephalopathy Early infantile epileptic encephalopathy with suppression burst Other symptomatic generalized epilepsies not defined above Specific syndromes Diseases in which seizures are a presenting or prominent feature
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Table 1 (Continued ) Epilepsies and syndromes undetermined as to whether they are focal or generalized International classification of epilepsies and epileptic syndromes With both generalized and focal seizures
ICD-8
ICD-10
90.9a
Neonatal seizures
G40.5 (1.8%)
Special epileptic syndromes
Epilepsy with continuous spike-waves during slow wave sleep
G40.6 (8.5%)
Acquired epileptic aphasia (Landau-Kleffner syndrome)
G40.7 (1.4%)
Grand mal seizures, unspecified (with or without petit mal) Petit mal, unspecified (without grand mal seizures)
Neonatal seizures
345.99 (45.4%)
Severe myoclonic epilepsy in infancy
345.19 (6.9%)
Epilepsia alia et non specificata Convulsiones universales
Other undetermined epilepsies not defined above Without unequivocal generalized or focal features. All Without unequivocal generalized cases with generalized or focal features. All cases with or focal features generalized tonic clonic seizures where clinical and EEG findings do not permit classification as clearly generalized of localization-related Special syndromes, and provoked and single seizures
40.9 (56.0%)
ICD-8
International classification of epilepsies and epileptic syndromes Situation-related seizures
G40.8 (6.4%)
780.20a
Isolated seizures or isolated status epilepticus Seizures occurring only when there is an acute metabolic or toxic event due to factors such as alcohol, drugs, eclampsia, nonketotic hyperglycemia
780.21a 780.29a
ICD-10
Convulsiones e furore Convulsiones febriles Convulsiones
R56.0a
Convulsiones febriles
R56.8a
Convulsions, others and unspecified
J. Christensen et al.
Febrile convulsions
Other epilepsy not specified whether partial or generalized type Epilepsy, unspecified
G41.8 (0.1%) G41.9 (0.7%)
G41.2 (0.1%)
We identified 90,994 epilepsy diagnoses among 88,781 persons; 2171 (2.5%) persons had two or more epilepsy diagnoses on the first admission with epilepsy. There were 49,521 epilepsy diagnoses among 48,667 persons based on ICD-8, and 41,473 epilepsy diagnoses among 40,167 persons based on ICD-10. There were 53 persons registered with both an ICD-8 and an ICD-10 diagnosis. For each of the diagnoses we calculated the proportion of diagnoses used (in %) for ICD-8 and ICD-10 separately. a These ICD-8/ICD-10 codes were not included as epilepsy.
345.29 (1.2%) Status epilepticus
G41.1 (0.1%)
G41.0 (0.8%)
ICD-8 International classification of epilepsies and epileptic syndromes
Status epilepticus
Table 1 (Continued )
Status epilepticus
ICD-10
Generalized tonic/clonic status epilepticus (grand mal) Non-convulsive status epilepticus absence type (petit mal) Non-convulsive status epilepticus complex—partial type Status epilepticus, other type Status epilepticus, unspecified
Validation of epilepsy diagnoses in the Danish National Hospital Register
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from each group of patients with a first diagnosis of epilepsy with complex focal seizures and patients with a first diagnosis of primary generalized epilepsy. Thus, we obtained a total sample of 200 patients with an epilepsy diagnosis in the Danish National Hospital Register. The number of cases evaluated (200) was set by time and financial constrains. This study was approved by the Danish Data Protection Agency, the Danish National Board of Health, and the head of the clinical departments. The medical records were retrieved from hospitals all over Denmark. The following information was extracted from the medical records: age, gender, date of first seizure, date of first registration in the Danish National Hospital Register, seizure type, EEG findings, and CT/MRI findings. One of the authors (P.S.), who is a consultant in adult neurology and trained in diagnosing and treating patients with epilepsy, classified the patients according to ILAE criteria (Commission, ILAE, 1981, 1989, 1993) into: (1) epilepsy or (2) not epilepsy. Epilepsy diagnoses were categorized into: (a) definite epilepsy or (b) probable epilepsy, and patients were given the latter label if the information from medical records on history of epilepsy and use of antiepileptic drugs made it likely that the patient had epilepsy, but information was missing needed to make a definite diagnosis (e.g. seizure presentation or EEG findings). Subsequently, the epilepsies were classified into the following syndrome categories: (a) focal epilepsy with simple focal seizures, with and without secondarily generalized seizures; (b) focal epilepsy with complex focal seizures, with and without secondarily generalized seizures; (c) primary generalized epilepsy; (d) unclassifiable epilepsy. The physician (P.S.) was blinded with regard to the specific epilepsy syndrome registered in the Danish National Hospital Register.
Results Validation process Medical records were collected from 57 departments at 41 hospitals. Medical records were missing for 12 (6%) patients. In the remaining 188 medical records, we found information on neuroimaging in 90 (48%) patients (MRI in 25 (28%) of patients and CT in 65 (72%) of patients) and EEG in 150 (80%) patients.
Epilepsy diagnosis Overall, the epilepsy diagnosis was confirmed in 153 patients (definite epilepsy, n = 131, probable epilepsy, n = 22), corresponding to a positive predictive value of 81% (95% CI: 75—87%) (the probability of a patient having epilepsy given this patient is registered with a diagnosis of epilepsy). We calculated a positive predictive value for epilepsy assuming that all 12 patients with missing information did not have epilepsy. This ‘‘worst case scenario’’ gave a positive predictive value for epilepsy of 77% (95% CI: 70—82%). The positive predictive value of an epilepsy diagnosis was 84% (95% CI: 75—91%) among the 83 patients diagnosed according to ICD-8 (1977—1993), and 79% (95% CI: 70—86%) among the 105 patients diagnosed according to ICD10 (1994—2002). Among 150 persons diagnosed with epilepsy at a specialized department (pediatrics, neurosurgery, and neurology), 125 had a diagnosis of definite or probable epilepsy, corresponding to a positive predictive value of 83% (95% CI: 76—89%). Among 180 medical records with valid
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J. Christensen et al.
Table 2 Agreement between a validated epilepsy diagnosis based upon ILAE criteria and a register diagnosis in the Danish National Hospital Registry using WHO’s International Classification of Disease (ICD-8/ICD-10) Validated diagnosis according to ILAE criteria (epilepsy syndrome)
Register diagnosis in the Danish National Hospital Register (based on WHO’s ICD-8/ICD-10) All epilepsy diagnoses (N (%))a
Epilepsy syndrome diagnoses (N (%)) Epilepsy with complex focal seizuresb
Primary generalized epilepsyc
Total (N (%))
Focal epilepsy (simple partial) Focal epilepsy (complex partial) Primary generalized epilepsy Not classifiable epilepsy
15 (15) 23 (23) 11 (11) 24 (24)
5 (10) 28 (56) 5 (10) 5 (10)
3 (6) 5 (10) 17 (34) 12 (24)
Not epilepsy Single seizure Other
10 (10) 10 (10)
0 (0) 4 (8)
4 (8) 7 (14)
14 (7) 21 (10.5)
7 (7)
3 (6)
2 (4)
12 (6)
100 (100)
50 (100)
50 (100)
200 (100)
Missing information Total
23 55 33 41
(11.5) (27.5) (16.5) (20.5)
In a total sample of 200 patients registered with an epilepsy diagnosis, 100 were sampled from the entire population registered with epilepsy, 50 were sampled from the population with a syndrome diagnosis of epilepsy with focal seizures and 50 were sampled among patients with a syndrome diagnosis of primary generalized epilepsy. a Epilepsy—–ICD-8: 345; ICD-10: G40—G41. b Epilepsy with complex focal seizures—–ICD-8: 345.31; ICD-10: G40.2. c Primary generalized epilepsy—–ICD-8: 345.09, 345.10, 345.11; ICD-10: G40.3.
information on time of first seizure, 64% were registered in the Danish National Hospital Register within a year after the first seizure, and 90% were registered within 5 years.
Seizure diagnosis Among the 35 patients who did not meet the epilepsy criteria, the reason for 14 patients was that only one unprovoked seizure episode was reported. Thus, 167 out of 188 patients registered with epilepsy had a seizure disorder corresponding to a positive predictive value for seizure disorder of 89% (95% CI: 83—93%). Assuming that all patients with missing records (n = 12) did not have an unprovoked seizure episode, we calculated a positive predictive value for seizure disorder. This ‘‘worst case scenario’’ gave a positive predictive value for seizure disorder of 84% (95% CI: 78—88%). Diagnoses in the remaining patients who did not fulfill the epilepsy diagnosis were: observation for epilepsy (but diagnosis not confirmed) (n = 6), syncope (n = 3), headache (cephalagia) (n = 2), myoclonia (n = 2), bradycardia/respiratory problems (n = 2), behavioral problems (n = 2), febrile seizure (n = 1), psychogenic seizures (n = 1), dyskinesias (n = 1), and mental retardation (n = 1). Among the six patients, who were considered ‘‘under observation for epilepsy’’, none had acute symptomatic seizures.
Epilepsy syndrome Among patients diagnosed with complex focal epilepsy in the Danish National Hospital Register, we found that 28 of 47 fulfilled the ILAE criteria for complex focal epilepsy (positive predictive value 60%; 95% CI: 44—74%) (Tables 1 and 2).
Among patients diagnosed with primary generalized epilepsy in the Danish National Hospital Register, we found that 17 of 48 fulfilled the ILAE diagnostic criteria for primary generalized epilepsy (positive predictive value 35%; 95% CI: 22—51%) (Tables 1 and 2).
Discussion Validity of the epilepsy diagnosis We found that 81% of persons registered with epilepsy in the Danish National Hospital Register fulfilled the ILAE criteria for an epilepsy diagnosis. Although care should be taken when extending these finding to other populations, the results are quite similar to what was found in a hospital-based register in Stockholm, Sweden covering the years 1980—1989 (Tomson, 2000). Among 171 patients admitted for inpatient care with a diagnosis of epilepsy, the epilepsy diagnosis was found to be correct in 79% of the cases (Tomson, 2000). A recent paper from North Jutland County, Denmark compared the physician-recorded diagnosis with the hospital discharge diagnosis in 69 children hospitalized with epilepsy between 1998 and 2000 (Ehrenstein et al., 2006). They found a positive predictive value of 75% for epilepsy (Ehrenstein et al., 2006). Data from epilepsy patients enrolled in the Lovelace Health Plan in Albuquerque, New Mexico between 1996 and 1998 showed that corroboration of an epilepsy diagnosis varied according to the number of diagnostic entries: 38.8% (1 entry), 69.2% (2—3 entries) and 100.0% (≥4 entries) (Holden et al., 2005a,b). The authors combined data from various sources to develop an algorithm based on the ICD-9 diagnosis of
Validation of epilepsy diagnoses in the Danish National Hospital Register epilepsy, the use of diagnostic procedures (e.g. neuroimaging and EEG), and use of antiepileptic drugs. The model with the best prediction of epilepsy used ICD-9 diagnoses of epilepsy and antiepileptic drugs as predictors for epilepsy (positive predictive value 84%)(Holden et al., 2005a,b). Our study was based on the first diagnosis of epilepsy, and we could probably have increased the predictive value significantly by restricting the cohort to patients with ≥4 entries. However, most epidemiological studies are likely to use the first diagnosis to avoid survival bias or a restriction to the most severe cases (Christensen et al., 2005b; Vestergaard et al., 2007).
Validity of a seizure diagnosis We excluded patients with single seizures according to current guidelines for epidemiologic studies on epilepsy (Commission, ILAE, 1993). We therefore excluded patients who may have been considered epilepsy patients in clinical practice (e.g. patients with specific syndromes defined by certain EEG patterns or epilepsy associated with intracranial tumors). Although not all patients would later fulfill the diagnostic criteria for epilepsy (Annegers, 2004), our findings most likely underestimated the ‘‘true’’ predictive value of the epilepsy diagnosis. Other population-based studies in epilepsy have included patients with single seizure episodes and patients with acute symptomatic seizures (Annegers et al., 1999; Cockerell et al., 1997; Forsgren et al., 1996; Jallon et al., 1999). Broadening the epilepsy definition beyond the ILAE definitions to include seizure disorders in general increased the predictive value of an epilepsy diagnosis to 89% in the present study, identical to findings from an assessment in 69 children reporting a positive predictive value for seizures of up to 89% (Ehrenstein et al., 2006).
Validity of the syndrome diagnosis We found a low predictive value when we focused on the ICD diagnosis of complex focal epilepsy and primary generalized epilepsy. One reason may be that the diagnosis of epilepsy is essentially clinical (Commission, ILAE, 1989), and despite high-quality diagnostic procedures (e.g. video-EEG), diagnostic certainty is not always possible. Another reason for the low predictive value is provided by comparing the terminology and classification of epilepsy syndromes as defined by ILAE with the classification and the terminology used in WHO’s ICD-8/ICD-10, which shows that there are major differences (Table 1). Accordingly, the proportion of patients classified with each of the ICD codes seems to vary a great deal between ICD-8 and ICD10—–not least for codes for primary generalized epilepsy (Table 1). Hopefully, future versions of ICD and ILAE guidelines will be more comparable (Annegers, 2004; Wolf, 2003). The ICD has undergone several changes and has been used to varying degrees over time. The IDC-9, for example, has never been implemented in Denmark. However, we did not identify important difference in the predictive value of an epilepsy diagnosis from ICD-8 to ICD-10.
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Completeness of the epilepsy diagnosis in the Danish National Hospital Register In this study, we did not assess the completeness of the epilepsy diagnosis in the Danish National Hospital Register. Extending the diagnoses to include codes for convulsions would probably increase the completeness, but lower the predictive value (Annegers, 2004; Holden et al., 2005a). We believe severe cases of epilepsy are most likely hospitalized and the Danish National Hospital Register includes also outpatients and therefore less severely affected cases of the epilepsy population compared with other hospitalised based registers (Tomson and Forsgren, 2003). Furthermore, most patients with epilepsy will probably come in contact with the hospital system at some point in time and thereby be included in the register since the register includes all diagnoses, not only the cause for hospitalization (the register allows for up to 20 diagnoses per admission or contact). Furthermore, patients referred for diagnostic procedures (e.g. EEG or MRI) will be included if they have epilepsy when examined. This is supported by the finding that 64% of patients with epilepsy were included in the register 1 year after the first seizure. The register includes patients from both specialized and non-specialized departments, probably adding to a more complete registration of cases similar to other population-based studies (Annegers et al., 1999; Cockerell et al., 1997; Forsgren et al., 1996; Jallon et al., 1999). The Danish National Hospital Register allows tracing persons over several decades owing to the unique identification in the Danish Civil Registration System, thereby ensuring a minimal loss at follow-up and preventing selection bias. In addition, the large population included in the Danish National Hospital Register provides a possibility to study rare events and is therefore a valuable data source for studying causes and consequences of epilepsy. Although ad hoc research studies using primary data will be able to get better diagnostic data and will be able to identify people who qualify for the diagnoses but never reach the hospital, these studies may be subject to sources of bias that do not compensate for better diagnostic data. Most ad hoc studies have low response rates, and long-term follow-up is very difficult to achieve for all. Furthermore, large-scale ad hoc studies are very expensive. Use of registers may offer a cheaper and at times even a methodologically superior alternative.
Acknowledgements We are indebted to Birgitte Jensen Hanner for enduring the hard work of collecting and systematizing information from the medical records. The study could not have been performed without help from the hospital secretarial staff at the involved departments. We would like to thank Carsten Bødker Pedersen and Marianne Gørtz Pedersen for help with the retrieval of epilepsy cases from the Danish National Hospital Register and with the calculation of proportion patients registered with the individual epilepsy codes. The study was supported by the Danish Research Agency (grant no.: 22-02-0207), P.A. Messerschmidt and Wife’s Foundation, Managing Director Kurt Bønnelycke and Mrs. Grethe Bønnelyckes Foundation, Research Initiative of Aarhus Uni-
170 versity Hospital, and Aase and Ejnar Danielsen’s Foundation. The Danish National Research Foundation funds the activities of the Danish Epidemiology Science Center.
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