Introduction

A Consensus Development Conference on Febrile Seizures was held at the National Institutes of Health on May 19-21, 1980. The purpose of the Conference was to bring together practicing physicians, research scientists, consumers, and others in an effort to reach general agreement on the risks of sequelae in children with febrile seizures and to compare them with the potential risks and benefits of prophylaxis with anticonvulsants.

On the first two days of the meeting, a consensus development panel and members of the audience reacted to evidence presented on the following questions:

• What is a febrile seizure?
• What are the risks facing the child who has a febrile seizure?
• What can chronic or intermittent prophylaxis accomplish in reducing those risks?
• What are the potential risks of prophylaxis, using the available forms of therapy?
• What is a rational approach to management of children with febrile seizures? Which children should be considered for prophylaxis?
• Are further clinical, experimental, or epidemiologic studies necessary?

The members of the consensus development panel represent the disciplines involved with treating and evaluating management of children with febrile seizures. The physicians were nominated for their role on the panel by four specialty medical associations: the American Academy of Pediatrics, the American Academy of Neurology, the American Academy of Family Physicians, and the Child Neurology Society. The panel met following the formal presentations and discussions to examine and debate the issues, based on the evidence presented. This summary is the result of these deliberations.

What Is a Febrile Seizure?

A febrile seizure^* is an event in infancy or childhood, usually occurring between three months and five years of age, associated with fever but without evidence of intracranial infection or defined cause. Seizures with fever in children who have suffered a previous nonfebrile seizure are excluded. Febrile seizures are to be distinguished from epilepsy, which is characterized by recurrent nonfebrile seizures.

What Are the Risks Facing the Child Who Has a Febrile Seizure?

Children who suffer a febrile seizure generally enjoy normal health after the episode. They are, however, at some risk in several respects. Thirty to 40 percent of children who have a febrile seizure and who do not receive prophylactic therapy will experience a second. The seizure itself is frightening and frequently may be emotionally disturbing to the family. During a seizure, there is additionally, a minimal chance of physical injury. The occurrence of a second or subsequent febrile seizure does not, in itself, greatly change the risk of epilepsy.

A small percentage of children who have had a febrile seizure may have nonfebrile seizures, that is, epilepsy. Significant risk factors separate children at high risk of developing nonfebrile seizures from those at low risk. The high risk group, for which one study showed a 13 percent incidence of epilepsy, is characterized by the presence of at least two of the following risk factors:

• a family history of nonfebrile seizures.
• abnormal neurological or developmental status prior to febrile seizure.
• an atypical febrile seizure, such as a prolonged or focal seizure.

Only 2 to 3 percent of children who have none or one of the above risk factors subsequently develop nonfebrile seizures.

The child with febrile seizures may have a neurological deficit, such as mental retardation, motor deficit, and sensory and perceptual abnormalities. It is generally believed that when present, these central nervous system (CNS) deficits have usually antedated the febrile seizures. There is no convincing experimental or epidemiological evidence that these deficits reflect neurological injury occurring at the time of the febrile seizure.

What Can Chronic or Intermittent Prophylaxis Accomplish in Reducing Those Risks?

The only risk demonstrated to be affected by therapy is that of recurrence of a febrile seizure. Numerous studies show that the risk of recurrence of febrile seizures can be reduced by the continuous daily administration of phenobarbital at appropriate dosage to achieve minimum therapeutic blood levels (about 15 mcg/ml). Preliminary evidence suggests that the frequency of febrile seizures may also be reduced by the prompt administration of diazepam by rectum, or possibly other agents, at the onset of acute febrile illness. There is no evidence to suggest that phenytoin is effective in prophylaxis of febrile seizures.

What Are the Potential Risks of Prophylaxis, Using the Available Forms of Therapy?

The potential risks of continuous prophylaxis are those predictable side effects, toxic manifestations, or idiosyncratic reactions that may be peculiar to the anticonvulsant drug selected for therapy.

Drugs currently administered on a long-term basis to prevent febrile seizures are phenobarbital, diazepam, and valproic acid and, to a lesser extent, phenytoin and carbamazepine. Phenobarbital is by far the most commonly used agent.

Side effects and toxic reactions are reported in up to forty percent of infants or children receiving phenobarbitol. These reactions are usually of the following types:

1. Behavioral changes--hyperactivity to extreme irritability, and, rarely, somnolence.
2. Sleep pattern disturbances--prolonged nocturnal awakenings.
3. Interference with higher cortical or cognitive functions, e.g.,

   1. defect in short-term memory formation
   2. inattentiveness or decreased attention span
   3. defects in general comprehension.

Disturbances in behavior and patterns of sleep are not predictable. They are the cause of discontinuation of therapy in up to 25 percent of patients.

Animal and tissue culture studies, which are not at this time conclusive in regard to humans, raise questions as to more serious effects of phenobarbital and certain other anticonvulsant agents on the developing nervous system.

Phenobarbital is capable of enzyme induction and, therefore, may interact with other drugs. The induction of more rapid metabolism of acetaminophen (a major antipyretic) may increase the risks of hepatotoxicity.

Phenobarbital has been used intermittently during febrile episodes to prevent recurrence of febrile seizures. In less than loading doses, this method is ineffective. When given in loading doses (10-15 mg/kg), phenobarbital produces somnolence, lethargy, and other behavioral manifestations.

Valproic acid has been shown to be an effective prophylactic agent in preventing recurrent febrile seizures. Few serious side effects and toxic reactions occur, however, gastrointestinal upset, toxic hepatitis, pancreatitis, and other side effects have been reported. Behavioral side effects are rare and disturbances in higher cortical function have not been reported. Liver function studies should be monitored periodically in patients on prolonged valproic acid therapy.

Diazepam, given by rectum, has been reported to be effective in the prophylaxis of seizures during febrile episodes. Side effects and toxic reactions have been rare, though sedation has been observed.

A report, however, did find that antipyretic therapy was not effective in preventing febrile seizures. Acetaminophen and aspirin both produce relatively prompt lowering of temperature and both are relatively free of side effects and toxic reactions.

What Is a Rational Approach to Management of Children With Febrile Seizures? Which Children Should Be Considered for Prophylaxis?

A rational approach to the management of febrile seizures should take into account that the long-term prognosis is excellent, that prophylaxis reduces the risk of subsequent febrile seizures, and that there is no evidence that prophylaxis reduces the risk of subsequent nonfebrile seizures.

An initial workup of febrile seizures should include a complete history and complete pediatric and neurological examination, including characterization of the febrile illness, degree of temperature elevation and complete description of the febrile seizure. If a CNS infection is suspected, a lumbar puncture is indicated.

The role of the electroencephalogram (EEG) in the workup of febrile seizures remains controversial. Abnormal EEG's do not reliably predict the development of epilepsy in patients with febrile convulsions.

Other studies, such as a complete blood count, measurement of levels of serum electrolytes, calcium, and glucose in the blood, and skull x-ray or computerized (CT) scanning of the brain are rarely useful in the uncomplicated febrile seizure.

Febrile convulsions rarely presage complex partial seizures or other forms of epilepsy and are generally benign and self-limited.

Anticonvulsant prophylaxis in therapeutic levels may be considered under any the following conditions:

1. In the presence of abnormal neurological development (e.g., cerebral palsy syndromes, mental retardation, microcephaly).
2. When a febrile seizure is:

   1. longer than 15 minutes, or
   2. focal, or
   3. followed by transient or persistent neurological abnormalities
3. History of nonfebrile seizures of genetic origin in a parent or sibling.

The physician occasionally may elect, in certain selected cases, to provide anticonvulsant treatment when a patient has multiple febrile seizures or when seizures occur in an infant under the age of 12 months.

When anticonvulsant prophylaxis is instituted, it is usually continued for at least two years or one year after the last seizure, whichever is the longer period of time. Discontinuation of therapy should be done slowly over a one- to two-month period.

Parents and others who are responsible in the care of young children play a key role in the prevention and management of febrile seizures. Family education and counseling should address:

• the relatively benign nature of febrile seizures;
• the recognition of and management of fever;
• the use of antipyretic agents;
• medication and compliance;
• side effects of medication;
• first aid for a seizure; and
• when and how to seek emergency assistance, if needed.

Educational materials may be an effective means to complement the physician's efforts toward family education.

Since nurses and allied health professionals, health educators, and social workers, are important in family education and counseling, they should receive adequate information in the management of febrile seizures.

Efforts should also be directed to disseminating this knowledge to the public, including day care centers, through mass media and other means.

Are Further Clinical, Experimental, or Epidemiologic Studies Necessary To Help in Answering These Questions?

Certain important questions remain unanswered. Studies are needed to address these issues.

1. Determination of risk factors predicting an initial febrile seizure.
2. Continuation of the present efforts to follow into adulthood children who have had a history of febrile seizures. This followup should include exploration of any association between febrile seizures and learning disorders, epilepsy, behavior aberrations, intellectual development, and changes in EEG.
3. Continued efforts to clarify the role of anticonvulsant treatment in febrile convulsions. Can evidence be obtained as to whether anticonvulsant treatment is able to:

   1. alter the probability of developing epilepsy at some later date?
   2. alter the probability of development of other neurological sequelae, e.g., lowered IQ?
   3. alter psychological and behavioral characteristics?
4. Pharmacological Studies

   1. What anticonvulsants are safe and effective in the chronic prophylaxis of febrile convulsions? What is the proper dosage and the therapeutic blood level?
   2. What anticonvulsants are safe and effective for short-term prophylaxis of febrile convulsions? What is the proper dosage and the therapeutic blood level?
   3. What are the long-term risks of the use of the above anticonvulsants?
   4. Does phenobarbital enhance the possible carcinogenic effects of other drugs or chemical agents in humans?
5. Controlled study of antipyretic measures with the onset of febrile illness as a means of decreasing the risk of recurrence of febrile seizures.
6. Continuation of experiments of the effects of drugs on brain growth and development, utilizing animal and tissue culture techniques.
7. Continuation of animal experiments to clarify the effects of single recurrent seizures on brain maturation and development, utilizing both experimental animal models and kindling techniques.

Consensus Development Panel

• Edwin L. Kendig, Jr., M.D. (Chairperson),
• Professor of Pediatrics
• Virginia Commonwealth University
• Medical College of Virginia
• Richmond, Virginia

• Paul R. Dyken, M.D., Professor and Chief
• Pediatric Neurology
• Medical College of Georgia
• Augusta, Georgia

• Nyrma Hernandez,
• Deputy Executive Director for Program Services,
• Epilepsy Foundation of America,
• Washington, D.C.;

• Marion C. McKee, M.D., F.A.A.P.,
• Clinical Professor of Pediatrics,
• University of Vermont,
• Director of Child Development Clinic,
• Vermont State Health Department,
• Burlington, Vermont;

• Hart deC. Peterson, M.D.,
• Associate Attending Neurologist and Pediatrician,
• New York Hospital-Cornell Medical Center,
• New York, New York;

• Nelson G. Richards, M.D., Private Practice,
• Clinical Associate Professor of Neurology,
• Medical College of Virginia,
• Richmond, Virginia;

• Robert H. Shackelford, M.D.,
• Clinical Professor of Family Practice,
• Duke University, Bowman Gray, University of North Carolina and East Carolina University Medical Schools
• Mount Olive, North Carolina;

• Elbert E. Smith, M.D., Pediatrician,
• Kansas City, Missouri;

• B. J. Wilder, M.D.,
• Professor of Neurology and Neuroscience
• University of Florida College of Medicine
• Chief, Neurology Service,
• Veterans Administration Medical Center
• Gainesville, Florida;

• Janet Wittes, Ph.D., Associate Professor,
• Department of Mathematical Sciences,
• Hunter College of the City University of New York,

Speakers

• Dr. Robert J. Baumann
• Department of Neurology
• University of Kentucky Medical Center
• Lexington, Kentucky

• Dr. Robert Brodell
• Cumberland, Maryland

• Dr. Carol Camfield
• Department of Pediatrics
• I. W. Killam Hospital for Children
• Halifax, Nova Scotia
• CANADA

• Dr. Peter Camfield
• Department of Neurology
• I. W. Killam Hospital for Children
• Halifax, Nova Scotia
• CANADA

• Dr. Sidney Carter
• Blythedale
• Valhalla, New York

• Dr. Sanford Cohen
• Department of Pediatrics
• Pediatrics/Pharmaceutical Section
• Wayne State University School of Medicine
• Detroit, Michigan

• Dr. Fritz E. Dreifuss
• University of Virginia Medical Center
• Department of Neurology
• Charlottesville, Virginia

• Dr. Marvin A. Fishman
• Head, Section on Child Neurology
• Baylor College of Medicine
• Houston, Texas

• Dr. Alan B. Forsythe
• Supervising Statistician
• Department of Biomathematics
• University of California
• Los Angeles, California

• Dr. John Freeman
• Associate Professor of Neurology
• Johns Hopkins Hospital
• Baltimore, Maryland

• Dr. Allen Hauser
• Servievsky Center
• Columbia University
• New York, New York

• Dr. Alan Leviton
• Boston Children's Hospital
• Boston, Massachusetts

• Dr. Samuel Livingston
• Associate Professor of Pediatrics, Emeritus
• Executive Director, Epilepsy Clinic
• Johns Hopkins University
• Baltimore, Maryland

• Dr. J. Gordon Millichap
• Professor of Neurology and Pediatrics
• Northwestern University
• Chicago, Illinois

• Dr. Solomon L. Moshe
• Albert Einstein College of Medicine
• Department of Neurology
• Bronx, New York

• Dr. James G. T. Nealis
• Neurology Clinic
• Jacksonville, Florida

• Dr. Lester Frank Soyka
• Department of Pharmacology
• University of Vermont College of Medicine
• Burlington, Vermont

• Dr. Gregory Stores
• Consultant in Neuropsychiatry of EEG
• Park Hospital for Children
• Headington, Oxford
• ENGLAND

• Dr. Kenneth F. Swaiman
• Head, Division of Pediatric Neurology
• University of Minnesota Hospital
• Minneapolis, Minnesota

• Dr. Ingrid Thorn
• University Clinics of Pediatrics
• Copenhagen County Hospital and Gentofte
• Copenhagen
• DENMARK

• Dr. Bea J. van den Berg
• Child Health and Development Studies
• Division of Biostatistics
• School of Public Health
• University of California
• Oakland, California

• Dr. Robert C. Vannucci
• Department of Pediatrics
• Milton S. Hershey Medical Center
• Hershey, Pennsylvania

• Dr. Sheila J. Wallace
• Welsh National School of Medicine
• Department of Child Health
• Cardiff
• WALES

• Dr. John T. Wilson
• Department of Pharmacology
• LSU Medical Center
• Shreveport, Louisiana

• Dr. Sheldon Wolf
• Neurologist
• Department of Neurology
• Southern California Permanente Medical Group
• Los Angeles, California

Conference Sponsors

• National Institute of Neurological and Communicative Disorders and Stroke
• National Institute of Child Health and Human Development
• Office of Medical Applications of Research

Footnotes

*A cerebral seizure is an abnormal, sudden, excessive electrical discharge of neurons (gray matter) which propagates down the neuronal processes (white matter), to affect an end organ in a clinically measurable fashion.

**Not yet available in the United States.

This statement was originally published as: Febrile Seizures. NIH Consens Statement 1980 May 19-21;3(2):1-10.

For making bibliographic reference to the statement in the electronic form displayed here, it is recommended that the following format be used: Febrile Seizures. NIH Consens Statement Online 1980 May 19-21 [cited year month day];3(2):1-10.

NIH Consensus Statements are prepared by a nonadvocate, non-Federal panel of experts, based on (1) presentations by investigators working in areas relevant to the consensus questions during a 2-day public session; (2) questions and statements from conference attendees during open discussion periods that are part of the public session; and (3) closed deliberations by the panel during the remainder of the second day and morning of the third. This statement is an independent report of the consensus panel and is not a policy statement of the NIH or the Federal Government.