Complex Febrile Seizures

Epilepsia, 37(2):12&133, 19% Lippmcott-Raven Publishers, Philadelphia 0 International League Against Epilepsy

Complex Febrile Seizures Anne T. Berg and Shlomo Shinnar School of Allied Health Professions, Program in Community Health, Northern Illinois University, DeKalb, Illinois; and *Departments of Neurology and Pediatrics, and The Comprehensive Epilepsy Management Center, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, U.S.A.

Summary: In the context of a prospective cohort study, we examined the associations between individual complex features of both first (n = 428) and recurrent (n = 240) febrile seizures and factors shown to predict outcome in children with febrile seizures. Thirty-fivepercent of first and 33% of recurrent febrile seizures had one or more complex features (focal onset, duration a10 min, or multiple seizures during the illness episode). There were strong correlations between focality and prolonged duration for both first and recurrent febrile seizures. A low fever at the time of the seizure was marginally associated with prolonged duration. Most factors associated with either recurrent febrile seizures or subsequent unprovoked seizures were not associated with either the initial seizure

being complex or the likelihood that a recurrence would be complex. However, in children with recurrent febrile seizures, complex features tended to repeat. This factor was statistically significant and particularly striking for prolonged duration. Genetic or other constitutional factors may explain why the prolonged feature recurs. Eleven (2.5%) children had three or four risk factors for recurrent febrile seizures and a first febrile seizure that was prolonged. Eight (72.7%) of them experienced a recurrent febrile seizure that was prolonged. This very small group of children may be candidates for abortive therapy to be administered at the onset of a recurrent seizure. Key Words: Complex febrile seizures-Febrile seizures-Focality-Duration-Status epilepticus.

Febrile seizures are common, occurring in 2 4 % of all children (14). Although now recognized as benign and self-limited, febrile seizures were once believed to be a form of and even a cause of epilepsy (5,6). Approximately one third of children who have a febrile seizure experience one or more recurrent febrile seizures, and 2-10% can expect to have one or more subsequent unprovoked seizures (7). Children at highest risk of developing unprovoked seizures and epilepsy are those who are neurologically abnormal, have a family history of epilepsy, or have complex febrile seizures (2,5,6,8). The concept of complex febrile seizures is derived from an earlier notion of epilepsy precipitated by fever (5) and as rigorously defined and studied by Nelson and Ellenberg (2). A complex febrile seizure has one or more of the following features: (a) partial onset, (b) prolonged duration (310 or 315 min have both been used) (248-lo), and (c) multiple (i.e.,

> 1) seizures in a single illness episode, generally in a 24-h period. Little is known about which children have complex febrile seizures and how such seizures are related to other predictors of outcome in children with febrile seizures. In addition, little is known about which children have recurrent febrile seizures that are complex and whether complex febrile seizures and individual complex features repeat themselves from one seizure to the next; this is of particular interest for prolonged seizures, which pose the greatest concern (11,12). We analyzed data from a prospective cohort of children followed from the time of a first febrile seizure to identify factors associated with having (a) an initial febrile seizure that is complex, and (b) a recurrent febrile seizure that is complex. METHODS

Children were prospectively identified through the pediatric emergency departments of Bronx Municipal Hospital Center, North Central Bronx Hospital, and Montefiore Medical Center, Bronx, New York, from June 1989 through May 1991 and in

Received August 11, 1995; revision accepted October 19, 1995. Address correspondence and reprint requests to Dr. A. T. Berg at School of Allied Health Professions, Northern Illinois University, DeKalb, IL 60115, U.S.A.

126

127

COMPLEX FEBRILE SEIZURES Yale-New Haven Hospital in New Haven, Connecticut, from June 1989 through January 1992. Details of the eligibility criteria and recruitment procedures for this cohort were reported previously (13). Interviewers trained by the investigators contacted the parents of patients, obtained informed consent, and administered a standardized interview in either English or Spanish. Each interviewer was trained to elicit information necessary for classifying complex features for each seizure. If the parent did not witness the seizure, the interviewer contacted the adult who had been with the child at the time of the seizure (e.g., daycare teacher) and obtained the information from that individual. We reviewed all emergency department records relevant to the seizure and illness and compiled a full description of the event based on the interview and the medical records. The presence of each of three complex features was recorded by 1 of the authors (S.S.). Any seizure of partial onset that secondarily generalized was classified as a focal onset seizure. A Todd’s paresis was considered to be evidence of a focal seizure. A seizure was prolonged if it lasted 2 10 min. In addition, we classified seizures as 2 15 min and as status epilepticus (230 min) (14). If a child had a flurry of seizures without fully regaining consciousness between seizures, the seizures were counted as one continuous seizure. If the total duration of such an episode was 330 min, the episode was counted as status epilepticus. A febrile seizure could have more than one complex feature. Interviewers obtained information about the family history of febrile seizures, single unprovoked seizures, and epilepsy. A history of developmental delay or other neurological abnormalities was based on parental report. Parents were also asked about the illness during which the initial febrile seizure occurred, especially the duration of recognized fever before that seizure ( < l , 1-24, >24 h). Emergency department records were reviewed for additional information about the illness, including the child’s temperature as it was measured by emergency department personnel when the child arrived at the hospital. Follow-up Parents were interviewed by telephone every 3 months to ascertain the occurrence of further febrile seizures. Whenever possible, medical documentation of the recurrence was obtained. Information about complex features of each recurrent febrile seizure was classified in the same way as the initial febrile seizures and without reference to the characteristics of the initial febrile seizure or sub-

sequent recurrent febrile seizures. We attempted to follow all children for at least 2 years from the date of their initial febrile seizure. Children (n = 26) with a subsequent unprovoked seizure were censored from further analysis of recurrent febrile seizures as of the first unprovoked seizure. Febrile seizures that had occurred before that time were included. A seizure was considered unprovoked if there were no acute precipitating circumstances to which the seizure might reasonably be attributed, such as a fever or head trauma (15).

Analysis Data were analyzed primarily by the chi-square test and chi-square test for trend for univariate associations. Fisher’s exact test was used when appropriate. Logistic regression was used for multivariable analyses (16). We performed three sets of analyses. In the first analysis, we examined factors associated with characteristics of the initial febrile seizure. In the second, we examined factors associated with having a recurrent febrile seizure that was complex; this focused only on children who had at least one recurrent febrile seizure and addressed the question: “In a child who has a recurrence, what is associated with at least one of the recurrences being complex?” To analyze characteristics of the initial febrile seizure as predictors of complex features during a recurrent seizure, all comparisons were made with children whose initial febrile seizure was simple. Finally, in the third analysis, we examined factors specific to the individual recurrent seizure such as the temperature during the particular illness. In this analysis, the individual recurrent seizure, not the child, was the unit of analysis. We examined the overall category of complex as well as its three specific components: focal onset, multiple seizures, and prolonged duration. Because duration has been classified in different ways by different investigators, we examined three definitions: 310, 2 1 5 , and 2 3 0 min. For ease of presentation, a “risk ratio” was used to summarize these associations. This represents the proportion of children with a particular complex feature (the outcome) in those with a characteristic of interest (the risk factor) relative to (divided by) the proportion in those without that characteristic. RESULTS

A total of 428 children were followed for a median of 29 months. Ninety-three percent were followed for at least 1 year, 87% for at least 18 months, and 83% for 2 2 years. In all, 136 (31.8%) had recurrent febrile seizures. Seventy-three (17.1%) had only Epilepsia, Vol. 37, NO. 2, 19%

128

A . T . BERG AND S . SHINNAR

one recurrence, 38 (8.9%) had two recurrences, and 25 (5.8%) had three or more recurrences: a total of 240 recurrent febrile seizures. Which children have a first febrile seizure that is complex? The initial febrile seizure was complex in 150 (35.0%) children. Sixty-nine (16.1%) had focalonset seizures, 59 (13.8%) had multiple seizures during the illness episode, and 56 (13.1%) had seizures of a10 min duration. Forty children (9.3%) had seizures of 215-min duration, and 22 (5.1%) met the criteria for status epilepticus: 330-min duration (14). There were 28 (6.5%) seizures that had two complex features and three (0.7%) seizures with all three features. The characteristics of the initial seizure were compared with factors that have been associated with either recurrent febrile seizures or subsequent unprovoked seizures (Table 1). These factors included a history of febrile seizures or of epilepsy in a first-degree relative, neurological abnormality by parent's report, age at first febrile seizure, temperature recorded in the emergency department, and duration of fever at the time of the seizure. In addition, we also examined the associations among the three complex features. There was a very strong association between the features of focal onset and long duration, but not one between having multiple seizures during the illness episode and either long duration or focality. There was also a trend for complex seizures, particularly prolonged ones, to occur in children who

were aged