Short-Term Outcomes of Children with Febrile ... - Wiley Online Library

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Center, Albert Einstein College of Medicine, Bronx, New York; the Departments of **Neurology and .... determined using the ambulance call sheets, emergency.
Epilepsia, 42(1):47–53, 2001 Blackwell Science, Inc. © International League Against Epilepsy

Clinical Research

Short-Term Outcomes of Children with Febrile Status Epilepticus *,†,¶Shlomo Shinnar, **,††John M. Pellock, ‡‡Anne T. Berg, *,§,¶Christine O’Dell, **Susan M. Driscoll, *,†Joseph Maytal, *,†,‡,¶Solomon L. Moshe, and **Robert J. DeLorenzo Departments of *Neurology, †Pediatrics, ‡Neuroscience, §Nursing, and the ¶Epilepsy Management Center, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York; the Departments of **Neurology and ††Pediatrics, Medical College of Virginia, Richmond, Virginia; and the ‡‡Department of Biological Sciences, Northern Illinois University, DeKalb, Illinois, U.S.A.

Summary: Febrile status epilepticus (SE) represents the extreme end of the complex febrile seizure spectrum. If there are significant sequelae to febrile seizures, they should be more common in this group. We have prospectively identified 180 children aged 1 month to 10 years who presented with febrile SE over a 10-year period in Bronx, New York, and Richmond, Virginia. They were compared with 244 children who presented with their first febrile seizure (not SE) in a prospective study done in the Bronx. The mean age of the children with febrile SE was 1.92 years, and of the comparison group, 1.85 years. Duration of SE was 30–59 min in 103 (58%), 60–119 min in 43 (24%), and ⱖ120 min in 34 (18%). Focal features were present in 64 (35%) of cases. There were no deaths and no cases of new cognitive or

motor handicap. Children with febrile SE were more likely to be neurologically abnormal (20% vs. 5%; p < 0.001), to have a history of neonatal seizures (3% vs. 0; p ⳱ 0.006) and a family history of epilepsy (11% vs. 5%; p ⳱ 0.05) and less likely to have a family history of febrile seizures (15% vs. 27%; p ⳱ 0.01) than were children in the comparison group. The shortterm morbidity and mortality of febrile SE are low. There are differences in the types of children who have febrile SE compared with those who experience briefer febrile seizures. Longterm follow-up of this cohort may provide insight into the relationship of prolonged febrile seizures and subsequent mesial temporal sclerosis. Key Words: Seizure—Status epilepticus—Epilepsy—Children—Etiology.

Febrile seizures are the most common seizures that occur in children. Between 2% and 5% of young children in the United States and Western Europe experience at least one febrile seizure (1–8). Although it is generally accepted that most febrile seizures are benign (1,3–5,9– 19), there is still some concern that prolonged febrile seizures may cause brain damage or neurological sequelae (20–31). The issue of whether prolonged febrile seizures are associated with the development of mesial temporal sclerosis (MTS) and intractable mesial temporal lobe epilepsy in later life is one of the most controversial areas in epileptology today. A major obstacle to further research has been the lack of adequate numbers of cases. Recent reports of acute

changes suggesting hippocampal injury have been limited to children with very prolonged febrile seizures (13,15,21–24). In studies of febrile seizures, ∼4–5% last ⱖ30 min (3–5,9–11,32). Thus, few studies of febrile seizures have included a large number of children with very prolonged febrile seizures. Between 1984 and 1996, the authors prospectively identified 180 children with febrile status epilepticus (SE) both as part of prospective studies of febrile seizures (9,10,32) and of SE (17,33–36) and as part of ongoing surveillance for cases of febrile SE at our institutions. This article presents the short-term outcomes of these children and a comparison of their clinical characteristics with a cohort of children with a first febrile seizure recruited during the same period (9,10).

Accepted August 9, 2000. Address correspondence and reprint requests to Dr. S. Shinnar at Epilepsy Management Center, Montefiore Medical Center, 111 E. 210th St., Bronx, NY 10467, U.S.A. This work was presented, in part, at the Child Neurology Society Meeting, Baltimore, Maryland, October 1995.

MATERIALS AND METHODS Population Included in this study are 180 children, aged 1 month to 10 years, who presented with febrile SE. 47

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Bronx cohort The 91 children in the Bronx cohort of febrile SE were prospectively recruited from 1984 to 1996. Some (n ⳱ 32) were recruited as part of the prospective portion of a study of SE (17,33) from January 1985 to June 1987, and some as part of a study of first febrile seizures (n ⳱ 10) from June 1989 to May 1991 (9,10,32). Children were seen at the affiliated hospitals of the Albert Einstein College of Medicine, Bronx, New York, including Montefiore Medical Center, Bronx Municipal Hospital Center, and North Central Bronx Hospital. Details of those studies, which included other children as well, have been previously published (9,10,17,32,33). The remainder (n ⳱ 49) were recruited by one of the authors (S.S.) as part of ongoing prospective surveillance of febrile SE at Montefiore Medical Center and have not been previously reported. One child who was initially recruited to the study was subsequently excluded. The child had a 5-min generalized tonic–clonic seizure and fever. There was a history of diarrhea and vomiting the previous day, evaluated in the emergency department and sent home. The child remained lethargic with persistent vomiting. Nineteen hours after initial seizure, another 5- to 10-min seizure occurred, which resolved without treatment. When seen again in the emergency department, the child was crying. However, ∼20 min later, the child had a 45-min seizure, which was treated with intravenous lorazepam (LZP) followed by phenytoin (PHT). The child never woke up and was clinically brain dead a short time thereafter. Computed tomography (CT) scan showed diffuse cerebral edema. Laboratory values of significance included a WBC of 3,200 with 10% bands, 49% polys, 35% lymphocytes, and 3% monocytes. Autopsy findings included diffuse cerebral edema and colitis. The child’s sibling was later diagnosed with shigellosis. Therefore, in retrospect, the most likely diagnosis was shigella encephalopathy. Richmond cohort The 89 children with febrile SE in this cohort were prospectively recruited from 1984 to 1994. They include 62 children recruited between July 1989 and 1994 as part of a large ongoing population-based study of SE cases in the Richmond area that started in July 1989 (34–36). Also included are 27 children prospectively identified by another of the authors (J.M.P.) from 1984 to 1989 as part of ongoing surveillance of childhood SE at the Medical College of Virginia and who were not included in prior reports. Details of the recruitment criteria and overall data for the population-based study in the Richmond area were previously published (34–36). Comparison group The comparison group was selected from a group of children with a first febrile seizure prospectively reEpilepsia, Vol. 42, No. 1, 2001

cruited from June 1989 through May 1991 at Jacobi Medical Center, North Central Bronx Hospital and Montefiore Medical Center in the Bronx and from June 1989 through January 1992 at Yale New Haven Hospital, New Haven, Connecticut. Details of the inclusion and exclusion criteria and outcomes for this cohort have been previously published (9,10). To provide a comparison group from the same geographic source of care, the comparison group used for this analysis was limited to those children recruited in the Bronx. We further excluded the 10 children in this cohort with febrile SE, as they are included in the Bronx cohort of children with febrile SE. The comparison group therefore includes 244 children including 168 with a first simple febrile seizure and 76 with a first complex febrile seizure (excluding febrile SE) (10). This is a hospital-based cohort, as is the febrile status epilepticus cohort. Definitions Status epilepticus was defined as any seizure lasting ⱖ30 min or recurrent seizures lasting a total of 30 min without fully regaining consciousness (33,34,37–39). In accordance with the International League Against Epilepsy (ILAE) guidelines for epidemiologic research (38), a febrile seizure was defined as a provoked seizure in which the sole acute provocation was fever (temperature 38.4oC) in a child older than 1 month without history of afebrile seizures. Children with previously abnormal neurologic function were included. Children with prior episodes of febrile seizures or febrile SE were included. However, if a child had two or more episodes of febrile status during the study period, only the first episode was counted. In accordance with the ILAE guidelines for epidemiologic research (38), children with prior neonatal seizures were included. Children with evidence of an acute central nervous system infection or electrolyte imbalance were excluded, as were infants younger than 1 month (16,38). This group with febrile SE is included in the category of a prolonged febrile seizure as defined by NIH Consensus Conference (4,11,16) and by the ILAE guidelines for epidemiologic research in epilepsy (38), as well as all previous epidemiologic studies of febrile seizures (3–12). It represents the extreme end of febrile seizures and has also been included in studies of childhood SE (33–41). For the comparison group, a simple febrile seizure was defined as an isolated, generalized tonic–clonic febrile seizure lasting