Demographic and Clinical Characteristics
A total of 308 children were screened at the time of their first seizure. Of these children, 148 were deemed ineligible after their initial screening for reasons that included: non–English-speaking guardian (n = 48), no guardian available for consent or sample collection (n = 28), chronic medical condition that increased the risk of seizure (n = 18), acute medical condition that increased the risk of seizure (n = 11), and preexisting developmental delay (n = 8). Guardians declined enrollment for 43 children. A total of 117 children were enrolled and evaluated. Of the 117 children enrolled, 78 (67%) had febrile first seizures, 34 (29%) had nonfebrile-illness first seizures, and 5 (4%) had unprovoked first seizures (). Among the 32 children for whom the Child Development Inventory was completed, no differences in development were found for any domain.
Demographics of Study Population According to Enrollment Group
Children in the nonfebrile-illness group were more likely to experience additional seizures during the 24 hours after their index seizure (59% compared with 28% in the febrile group; P = .002) but were not more likely to experience additional seizures during the following week (6% in both groups) (). Initial febrile seizures and nonfebrile-illness seizures were similar in duration (median: 2 minutes in both groups) and proportion with focal presentation (9% and 6%, respectively; P = .72). Children with first nonfebrile-illness seizures were less likely than children with first febrile seizures or first unprovoked seizures to have abnormal blood glucose results (14% and 71%, respectively; P = .002) according to normal laboratory ranges (); however, no child had a glucose level below 41 mg/dL.
Characteristics of Primary Seizure Event According to Primary-Seizure Enrollment Group and Gastrointestinal Illness Group
Illness Symptoms Concurrent With Index Seizure
Acute gastrointestinal illness (onset within 7 days before or after the index seizure) was present in a larger proportion of the nonfebrile-illness-seizure group compared with the febrile-illness-seizure group (47% and 28%, respectively; P = .05) (). Overall, 36 of 38 children with acute gastrointestinal illness developed diarrhea within the 5 days that led up to the index seizure, and 2 children developed diarrhea at days 2 and 3 after the index seizure. Both of these children presented with fever and rhinorrhea at the time of seizure, and 1 had a 2-day history of vomiting.
Acute Illnesses and Viral Pathogens That Accompanied First Seizure, According to Study Group
Children with acute gastrointestinal illness experienced multiple seizures within the first 24 hours significantly more often than children with febrile seizures (58% and 27%, respectively; P = .001) (). This association persisted after we controlled for fever in a logistic regression model (adjusted odds ratio: 3.3; 95% confidence interval [CI]: 1.4–7.7). None of the 38 primary seizures in the presence of acute gastrointestinal illness had focal presentation, compared with 9 (12%) of the 74 seizures in the nongastrointestinal illness group (P = .02) ().
Stool samples were available for rotavirus and norovirus testing from 64 children with a febrile seizure, 23 children with a nonfebrile-illness seizure, and 4 children with a first unprovoked seizure (). Rotavirus tests were performed for 3 additional children at the clinical laboratory of Seattle Children’s Hospital, and 2 were positive for rotavirus. Children with a first nonfebrile-illness seizure were more likely than those with a first febrile seizure to have a stool sample test positive for rotavirus (P = .02) and for norovirus (P = .05). No viruses were detected in 4 available stool samples from children with unprovoked seizures.
A total of 19 children (including 18 with acute illness) had serum samples and 5 children had CSF samples available for testing for rotavirus and norovirus (). Five children with rotavirus-positive stool samples had available serum samples, 1 of which tested positive for rotavirus RNA. This sample was from a child with a first febrile seizure and acute gastrointestinal illness. Only 1 CSF sample was available from the group of children with rotavirus-positive stool. This sample was positive for rotavirus RNA and was from a child with a first nonfebrile-illness seizure and acute gastrointestinal illness.
Fifty-nine stool samples had sufficient material for additional virus testing (). Enterovirus and parechovirus were detected only in the febrile group, whereas adenovirus and bocavirus were detected in both the febrile and nonfebrile-illness groups. At least 1 virus was detected in 46 children, and multiple viruses were detected in 7 children (5 in the febrile group and 2 in the afebrile group). No coinfections involving both rotavirus and norovirus were observed ().
EEGs were performed at the discretion of the consulting neurologist or primary care physician in 32 of 117 children. The EEG was performed an average of 26 days (interquartile range: 3–40) after the index seizure. The proportion of children with EEGs recorded within 3 days of the index seizure was not significantly different between children with normal and children with abnormal EEG findings (22% and 36%, respectively; P = .45, Fisher’s exact test). Abnormalities were identified on 14 of 32 EEGs (). Slowing or epileptiform discharges were identified in 3 children with first febrile seizure, 3 children with first nonfebrile-illness seizure, and 3 children with first unprovoked seizure. Of the 9 children with acute gastrointestinal illness who underwent EEG, 3 had EEG results that revealed abnormalities, but none showed focal slowing or epileptiform discharges ().
Children were followed for a total of 101 324 days (range: 1–1684 days; mean: 866 days). Mean follow-up time was similar among all study groups ().
The Kaplan-Meier failure estimates for any second seizure after the first week was 60% (95% CI: 25%–95%) for children with a first unprovoked seizure, 24% (95% CI: 12%–44%) for children with a first nonfebrile-illness seizure and 31% (95% CI: 21%–43%) for children with a first febrile-illness seizure. With the use of a Cox proportional hazards model to compare the risk of a second seizure, the prognosis for nonfebrile-illness seizures was not significantly different from that of febrile-illness seizures after we controlled for use of antiepileptic medication (). However, children who experienced acute gastrointestinal illness, regardless of fever, at the time of the index seizure had a significantly reduced risk of recurrent seizures, even after we controlled for the presence of fever at the time of the index seizure (). When we examined data for children with illness-associated seizures and controlled for antiepileptic drug use, we found that rotavirus and norovirus infection each conferred a reduced risk of seizure recurrence that was not statistically significant (hazard ratio: 0.30 [95% CI: 0.04–2.23] [rotavirus] and 0.49 [95% CI: 0.11–2.10] [norovirus]). Overall, the Kaplan-Meier failure estimates for a second seizure of any type were 11% (95% CI: 4%–28%) for children with gastrointestinal illness and 40% (95% CI: 29%–53%) for children with nongastrointestinal illness ().
Cox Regression Models for Risk of Future Seizure Recurrence of Any Type
Kaplan-Meier failure for seizure recurrence, according to study group and acute illness. GI indicates gastrointestinal.
Of the recurrent seizures that occurred, only 6 were nonfebrile, 2 in children with a first unprovoked seizure and 4 in children with a first nonfebrile-illness seizure without acute gastrointestinal illness (). The Kaplan-Meier failure estimates for a future nonfebrile seizure were 40% (95% CI: 12%–87%) for children with a first unprovoked seizure and 14% (95% CI: 5%–32%) for children with a first nonfebrile-illness seizure; no recurrent nonfebrile seizures were observed in children with a first febrile-illness seizure (). For children with nongastrointestinal illness, the Kaplan-Meier failure estimate for a nonfebrile recurrence was 9% (95% CI: 4%–19%). No nonfebrile recurrent seizures occurred in children with acute gastrointestinal illness at the time of their index seizure.
FIGURE 2 Kaplan-Meier failure for first nonfebrile seizure recurrence, according to study group and acute illness. No subsequent nonfebrile seizures were observed in children with first febrile seizures or in children with acute gastrointestinal illness. GI indicates (more ...)