The accuracy of the diagnosis of paroxysmal events in children
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Abstract
Objective: To assess the accuracy of the diagnosis of epileptic seizures in children.
Methods: The Dutch Study of Epilepsy in Childhood is a prospective hospital-based study of 881 children referred because of possible seizures. The diagnosis was based on predefined descriptive criteria, as applied by a panel of three pediatric neurologists. Children with a definite other diagnosis were excluded. All children with unclear events were followed up for 1 year and children with seizures were followed up for 2 years to assess the accuracy of the diagnosis.
Results: In 170 of 224 children seen after a single event, the incident was classified initially as epileptic, in 54 as unclear. In none of the 170 children did the diagnosis prove to be wrong. In four of the 54 children, recurrent episodes enabled a definite diagnosis of epilepsy. In 412 of the 536 children seen with multiple events, an initial diagnosis of epilepsy was made. After follow-up, this initial diagnosis was probably incorrect in 19. In contrast, seven of 124 children with multiple unclear episodes at intake later received the diagnosis epilepsy.
Conclusions: A false-positive diagnosis of epilepsy was made in 4.6%, whereas a definite diagnosis of epilepsy or seizure was delayed in 5.6% of children with multiple unclear events and in 7.4% of children with one unclear event.
Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the March 25 issue to find the link for this article.
The diagnosis of a single seizure or epilepsy is based on a description of the episodes and may be subject to error. To prove that a single event was an epileptic seizure is often impossible. Generally accepted and validated diagnostic criteria are lacking. The widely used International Classifications of Seizures1 and Epileptic Syndromes2 provide no guidelines for the diagnosis of epileptic seizures. They only permit classification once the diagnosis has been made.3,4⇓ Surprisingly, most clinical or epidemiologic studies do not mention patients in whom the diagnosis proved to be incorrect.5 The Dutch Study of Epilepsy in Childhood (DSEC) is a prospective hospital-based study of children with newly diagnosed possible single or multiple seizures.6-8⇓⇓ A panel of three pediatric neurologists classified the events as epileptic seizures, unclear episodes, or events of definitely other origin. Children with one or more unclear events were followed up for 1 year and children with a diagnosis of a first seizure or epilepsy for 5 years. In this part of the study, we describe the accuracy of the initial diagnosis after one or more paroxysmal events.
Patients and methods.
The prospective multicenter hospital-based DSEC started in 1988. After informed consent, we enrolled consecutively all children aged 1 month to 16 years who were referred because of a possible single seizure or epilepsy. Most children were referred directly by their general practitioner or by the pediatricians of the participating hospitals (who routinely refer all children with possible seizures to the departments of pediatric neurology). Some were first seen in the emergency department. We excluded children with only neonatal, febrile, or other acute symptomatic seizures as well as children who were referred from other hospitals for a second opinion.
The attending pediatric neurologist completed an extensive questionnaire on the description of the events including postictal signs, possible provoking factors, medical history, and family history. In addition, the descriptions of the episodes according to the letters to the general practitioners were made available to the panel judging the diagnoses (see below). We performed a standard EEG in each child. If this did not show epileptiform discharges, a recording after partial sleep deprivation or, in small children, during a daytime nap was made. Details on the recording and classification of the EEG have been described elsewhere.8 A brain CT scan was performed in all children unless anesthesia was required or the child had idiopathic generalized epilepsy with absences. Seventy-two percent of the children with one seizure and 66% of the children with multiple seizures had a CT scan. In former publications on the DESC, more extensive information concerning the results of imaging can be found.6,7⇓
A panel of three of four pediatric neurologists with at least 10 years of experience in pediatric epilepsy (H.S., A.C.B.P., O.F.B., and W.F.M.A.) judged whether the description of the ictal events fulfilled the predefined descriptive diagnostic criteria for seizures as adapted from an earlier Dutch study in adults9 (table E1 on the Neurology Web site). To prevent bias, none of the pediatric neurologists was allowed to judge his patients, but only those who were treated by one of the other panel members. These pediatric neurologists in 1988 founded the DSEC and have been involved in it since then. They discussed all 881 children referred during monthly sessions. Unanimous decisions were reached in all cases. The 121 children in whom another diagnosis was made were excluded. The study group consisted of 760 children: mean age 5.4 years, median age 4 years (25 to 75% range: 2 to 9 years); 367 were boys. A flow chart of all children in the study and their subgroups is presented in the figure. For a single event, the diagnosis was based exclusively on the description of the event without knowledge of the results of the EEGs or other ancillary studies. We considered a single unclear event in a child with an abnormal EEG not as an epileptic seizure, as epileptiform discharges are present in some children without any clinical seizures. In case of multiple events, however, the results of the EEGs were considered if the panel agreed based on their clinical experience that the events were suspect for seizures, although the criteria were not completely satisfied.
Figure. Flow chart of the 881 children with one or more possible seizures.
In the DSEC we followed up all children with a diagnosis of epilepsy for 5 years and all children with a single seizure for 2 years to assess the prognosis.6,7⇓ At 2 years, the accuracy of the original diagnosis was assessed. In an attempt to include all children with epilepsy in the DSEC, children with unclear events (including children with presumed pseudo-seizures) were followed for 1 year to assess whether new episodes might yield firm evidence for a definite diagnosis. An unclear event was defined as a paroxysmal event not considered as an epileptic seizure, but without another obvious explanation. After each new event, the patient was reevaluated and the diagnosis reconsidered. Point estimates regarding false-positive or false-negative diagnoses are given with their 95% CIs. The CIs were calculated according to the efficient-score method (corrected for continuity).10
Results.
Paroxysmal events.
Of the 881 children in the study group, 121 received a definite other diagnosis and were excluded from follow-up (see the figure). A total of 224 children were referred because of a single event. In 170 of these 224, the panel diagnosed a single seizure (table 1); 90 of them had at least one more event. During the follow-up period, doubts on the diagnosis seizure arose in none of the children with recurrent events, whereas the diagnosis was maintained in all children without a recurrence (false-positive rate, 0%; 95% CI, 0 to 2.8).
Table 1 Accuracy of the diagnosis of a single epileptic seizure
The panel was uncertain on the diagnosis of a first event in 54 children, of whom 14 had at least one more event. We eventually made a diagnosis of epilepsy after 1-year follow-up in five of these. After 2 years of follow-up, new doubts arose in one of these children. Her first event was associated with teeth brushing. We considered this event as uncertain diagnosis. Within 12 months, she had a second paroxysmal event. Her EEG showed epileptiform abnormalities; a diagnosis of epilepsy was made and an antiepileptic drug was prescribed. After about 20 months, a new event took place while her hair was being combed. Based on the description of this event and the circumstances during two of the three events (teeth brushing, hair combing) this was thought to be a hairdresser’s syncope,11 after which the diagnosis of epilepsy was again rejected. Altogether, the false-negative rate for the diagnosis of epilepsy was, therefore, four of 54 (7.4%; 95% CI, 2.4 to 18.7). The other nine children with a recurrence had syncope with myoclonic jerks (two) and benign paroxysmal vertigo, breath-holding spells, pseudo-seizures, and pavor nocturnus (one each), whereas in three children the diagnosis remained unclear. In the 40 patients without recurrence, the diagnosis remained unclear. Altogether, the sensitivity of the diagnosis “epileptic seizure” after a single paroxysmal event proved to be 97.7% and the specificity 100%.
At intake, the panel made a diagnosis of epilepsy in 412 children. This diagnosis was based on the description of the events in 367 children, and on the description combined with the EEG results in 45 children. During a 2-year follow-up period, doubts on the original diagnosis arose in 19 of 412 children (table 2; false-positive rate for the diagnosis of epilepsy, 4.6%; 95% CI, 2.9 to 7.2). Three of them were initially included based on the description of the events combined with the results of the EEG, which means a false-positive rate for the diagnosis of epilepsy in this group of 45 children of 6.7%; 95% CI, 2.3 to 17.9. The false-positive rate for the diagnosis of epilepsy in the 367 children diagnosed exclusively based on the description was 4.4%; 95% CI, 2.7 to 7.0%. The final diagnoses for all children are given in table 3. The diagnosis at entry was unclear in 124 children seen with multiple events. Of these, 75 had at least one new episode during follow-up. After 1 year, a diagnosis of epilepsy was made in seven children (see table 2; false-negative rate, 5.6%; 95% CI, 2.5 to 11.7), and in 36 another diagnosis was made. Table 3 presents the final diagnoses. In the group of 536 children with multiple events before intake, the sensitivity of the diagnosis “epilepsy” was 98.3%, the specificity 86.0%.
Table 2 Accuracy of the diagnosis of epilepsy
Table 3 Final diagnoses in 760 children referred with possible seizures
Based on the whole group of 760 children with single or multiple events, this means a sensitivity of (170+393)/(174+400) = 98.1% (95% CI, 96.5 to 99.0) and a specificity of (50+117)/(50+136) = 89.8% (95% CI, 84.3 to 93.6).
EEG results.
The EEG might be used to increase the diagnostic accuracy of single paroxysmal events. Because the diagnosis of the single events rested entirely on its clinical description, it was possible to calculate the sensitivity and specificity of epileptiform EEG abnormalities in children with a single paroxysmal event after follow-up. In the group of 174 patients with an epileptic seizure or epilepsy as the final diagnosis (170 from the group with a single seizure and four from the group with one unclear event, excluding the patient in whom new doubt arose), 97 patients had an EEG with epileptic abnormalities (sensitivity 55.7%). In the group of patients with another diagnosis, or in whom doubt remained, 11 of 50 patients had an epileptiform EEG (specificity 78.0%; table 4). The presence of epileptiform EEG abnormalities was in accordance with the diagnosis of an epileptic seizure in 89.8% of the children.
Table 4 Diagnostic value of the EEG after a single paroxysmal event
The EEGs showed epileptiform abnormalities in 285 of the 412 children with multiple epileptic seizures. In 45 of those, the diagnosis of epilepsy was based on the combination of the description of the event and the EEG, because the events themselves were not sufficiently clear. However, after follow-up, the diagnosis was doubted in three of them. In addition, in the group of 240 children with an initial clinical diagnosis of epilepsy and epileptiform EEG abnormalities, two children appeared not to have epilepsy after follow-up. In 27 of 124 children with multiple uncertain events, either the first or the second EEG showed epileptiform abnormalities. Of these 27, definite epilepsy was eventually diagnosed in only one. Therefore, epileptiform abnormalities confirm the diagnosis of epilepsy after multiple events in 90.1%, and their absence refutes this diagnosis correctly in 46.9% (sensitivity, 70.3%; specificity, 77.2%; table 5).
Table 5 Diagnostic value of the EEG after multiple events
Discussion.
In this study rigid diagnostic standards were applied for the diagnosis of a single seizure or epilepsy in childhood. The diagnosis was based on consensus between the members of a panel of experienced pediatric neurologists, using predefined diagnostic criteria. Unfortunately, a gold standard to confirm or refute the diagnosis of a seizure or of epilepsy is lacking. Instead, we tried to disprove the original diagnosis by assessing whether new episodes during follow-up might lead to another diagnosis. Using this approach, we found a false-positive rate for the initial diagnosis “single seizure” of 0% and for “epilepsy” of almost 5%. It should be noted that this method probably underestimates the number of incorrect diagnoses, because the diagnosis will not change if the child does not have a recurrence of the events during follow-up. Moreover, the low false-positive rate may be explained by the fact that the panel tended to prefer the diagnosis unclear and not seizure or epilepsy in case of any doubt or disagreement between the panel members.
In addition, we studied the fate of the children with an unclear diagnosis at enrollment. The false-negative rate was 7.4% for children recruited after a single unclear event and 5.6% for children enrolled after more unclear events. In other words, irrespective of the fact that a child was enrolled after one or more unclear events, one of every 15 children was not recognized to have epileptic seizures. However, none of the children experienced any harm due to this delay.
Most of the children in whom the diagnosis seizures was changed during follow-up, as well as the children with unclear events in whom a diagnosis became obvious during follow-up, turned out to have a harmless paroxysmal disorder (see table 3). The majority was not harmed by unnecessary delay of medical treatment. The only exception was the child with TIAs based on moyamoya disease diagnosed initially as epilepsy.
In view of the rigid standards we used in the diagnostic process (diagnosis by a unanimous decision of a panel of three experienced pediatric neurologists with use of predefined criteria), the figures found in our study may be a minimum estimate for the errors in everyday clinical and research situations. This should be kept in mind when judging studies on the prognosis of single seizures and epilepsy in children. We recommend that in this type of research, the initial diagnosis should be reconsidered after sufficient follow-up. From a clinical point of view, however, a false-negative diagnosis of epilepsy is probably less harmful for the patient than a false positive. A conservative approach in children with paroxysmal events of uncertain nature seems, as before, warranted.
Acknowledgments
Supported by the Dutch National Epilepsy Fund (Grants A72 and A85).
- Received February 19, 2002.
- Accepted November 16, 2002.
References
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