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Pediatrics in review 1997
Pediatrics in review 1997
Pediatrics in review 1997
Pediatrics in review 1997
Pediatrics in review 1997
Pediatrics in review 1997
Pediatrics in review 1997
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Pediatrics in review 1997

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  • 1. Febrile Seizures Deborah G. Hirtz Pediatrics in Review 1997;18;5 DOI: 10.1542/pir.18-1-5The online version of this article, along with updated information and services, is located on the World Wide Web at: http://pedsinreview.aappublications.org/content/18/1/5Pediatrics in Review is the official journal of the American Academy of Pediatrics. A monthlypublication, it has been published continuously since 1979. Pediatrics in Review is owned,published, and trademarked by the American Academy of Pediatrics, 141 Northwest PointBoulevard, Elk Grove Village, Illinois, 60007. Copyright © 1997 by the American Academy ofPediatrics. All rights reserved. Print ISSN: 0191-9601. Downloaded from http://pedsinreview.aappublications.org/ at Dahlgren Medical Library on January 9, 2012
  • 2. ARTICLEFebrile SeizuresDeborah G. Hirtz, MD* a similar study in which both febrile IMPORTANT POINTS and afebrile control children were 1. Most children who have febrile seizures do very well, and the risk of examined, a family history of febrile epilepsy is low. seizures, neonatal discharge 28 days 2. The earlier the age at which the first febrile convulsion occurs, the or later, parental report of slow more likely are recurrences. development, and child care atten- 3. Diagnostic laboratory tests never should be routine. Neuroimaging dance were risk factors for febrile rarely is indicated. seizures (Table 1). Another recent 4. Meningitis always should be ruled out, either clinically or by lumbar study found a correlation between puncture if indicated. low serum sodium levels and risk 5. Treatment has not been shown to reduce the risk of later epilepsy and carries a risk of side effects. for developing febrile convulsions. RECURRENCEDefinition are used because it has become clear After the first febrile seizure,Febrile seizures are the most com- through prospective epidemiologic approximately 33% of children willmon convulsive disorder in young studies that there is not nearly as experience one or more recurrences,children. As defined in a 1980 great a risk for development of and about 9% of children who haveNational Institutes of Health consen- epilepsy or recurrent afebrile febrile seizures will have three orsus conference, a febrile seizure is: seizures as had been attributed by more. The younger the child when Livingston to the seizures he called the first febrile seizure occurs, the “An event in infancy or early child- “epilepsy triggered by fever”. greater the likelihood of recurrence. hood, usually occurring between More recently, febrile seizures three months and five years of age, Most recurrences (75%) happen have been divided into two sub- within 1 year. A recent study has associated with fever but without groups: simple febrile seizures, shown an increased risk of recur- evidence of intracranial infection or defined cause. Seizures with fever which last fewer than 15 minutes rence to be associated with a shorter in children who have suffered a and are generalized, and complex duration of fever before the initial previous nonfebrile seizure are febrile seizures, which are pro- febrile seizure and a lower tempera- excluded. Febrile seizures are to longed, multiple within 24 hours, or ture. Family history of febrile be distinguished from epilepsy, focal. Children in either of these sub- seizures is another reported risk fac- which is characterized by recurrent groups may have a pre-existing neu- tor for recurrence. A family history nonfebrile seizures.” rologic abnormality or a family his- of afebrile seizures has beenThis definition excludes seizures tory of febrile or afebrile seizures. reported as a risk factor for recur-that accompany neurologic illnesses, rence in some studies, but not insuch as meningitis, encephalitis, or Epidemiology others. “Complex” febrile convul-toxic encephalopathy. Seizures in Febrile seizures occur in approxi- sions are not more likely to be fol-these instances do not carry the mately 2% to 4% of young children lowed by recurrences. Young age ofsame prognosis as febrile seizures in the United States, South America, onset and a family history of febrilebecause the underlying illness may and Western Europe. They are convulsions are the strongest andaffect the central nervous system. reported to be even more common most consistent predictors of recur- Febrile seizures have been dis- in Asian countries. Several large rence (Table 2).cussed in the medical literature since prospective studies have determinedthe time of Hippocrates, but it was that in approximately 20% of cases, EPILEPSYnot until the middle of the present the first febrile seizure was complex Although it has been reported thatcentury that they were recognized as (ie, lasted more than 15 minutes, febrile seizures preceded 15% ofa separate syndrome distinct from was focal, or involved at least twoepilepsy. An early classification pro- seizures within 24 hours). The mostposed by Livingston divided them common age of onset is in the sec-into “simple febrile seizures” and ond year of life. Febrile seizures are TABLE 1. Risk Factors“epilepsy triggered by fever.” He slightly more common in males. for a First Febrile Seizureincluded in the latter definitionfebrile seizures that were prolonged RISK FACTORS FOR A FIRST • Family history of febrile seizuresor focal or that occurred in a child FEBRILE SEIZURE • Neonatal discharge ≥28 dayswho has a family history of In studies comparing children who • Delayed developmentepilepsy. These definitions no longer have febrile seizures with febrile • Child care attendance controls, a higher temperature was a • Low serum sodium*Developmental Neurology Branch, National risk factor for the development of a • Very high feverInstitute of Neurological Disorders and febrile seizure, as was a history ofStroke, Bethesda, MD. febrile seizures in a close relative. InPediatrics in Review Vol. 18 No. 1 January 1997 5 Downloaded from http://pedsinreview.aappublications.org/ at Dahlgren Medical Library on January 9, 2012
  • 3. NEUROLOGY Febrile Seizures tis media. Children of preschool age TABLE 2. Risk Factors TABLE 3. Risk Factors are subject to frequent infections for Recurrence of for the Development and accompanying high fevers, Febrile Seizure of Epilepsy Following which in combination with a rela- Febrile Seizures tively low seizure threshold, allows • Young age for the common occurrence of • Suspect or abnormal development febrile seizures. • Family history of febrile before the first seizure Several recent reports have docu- seizures • Family history of afebrile mented the frequent presence of • Short duration of fever before human herpesvirus 6 (HHSV-6) in seizures the initial seizure cases of febrile seizures. HHSV-6 is • Complex first febrile seizure a recently identified etiologic agent • Relatively lower fever at the in roseola (exanthem subitum). In time of the initial seizure one series, the virus was cultured • Possible family history of from 8 (19%) of 42 patients who had GENETICS afebrile seizure a first febrile seizure, and titers rose Febrile seizures tend to occur in in 9 of the 34 (26%) who returned families, although the exact mode of for convalescent titers. The virus was inheritance is not known. Children not detected in 29 cerebrospinal fluidcases of childhood onset epilepsy, who have febrile seizures tend more (CSF) samples taken. In eightbecause febrile seizures are a much often to have a history of febrile patients who had a history of roseolamore common occurrence than convulsions in close relatives. There and multiple febrile convulsions,childhood epilepsy, fewer than 5% also may be a higher incidence of HHV-6 DNA was detected in theof children who have febrile afebrile seizures in the families of CSF sampled after a febrile convul-seizures actually develop epilepsy. children who have febrile seizures, sion; it was not evident in controls, Rates of epilepsy tend to be but the evidence is not as clear. The and it was documented in only onehigher in populations having febrile relative risk for epilepsy is higher in of seven children who had a singleseizures from selected sources such siblings of children who have febrile febrile seizure. It was postulated thatas hospital admissions or referrals to seizures, but not in other relatives. viral invasion of the brain mayspecialists. All types of epilepsy, Parents may ask about the risk of occur sometime during the acute ill-including absence, generalized tonic- febrile seizures in younger siblings of ness, and during subsequent ill-clonic, and complex partial, can be children who have febrile convul- nesses, be reactivated by fever.seen in patients who have a history sions. It is in the range of 10% toof febrile convulsions. 20%, but will be higher if the parents Clinical Aspects In the National Institute of Neu- have a history of febrile convulsions.rologic Disorders and Stroke Febrile seizures usually occur early(NINDS) Perinatal Collaborative in the course of a febrile illness, COMPLEX PARTIAL SEIZURESProject (NCPP), an increased risk often as the first sign. It commonly Although some authors believe that has been thought that the rate offor developing one or more afebrile febrile seizures may predispose theseizures was found among children increase of the fever is an important child to developing complex partial trigger, but there are no data to sup-in whom development was suspect seizures (CPS), the evidence is con-or abnormal prior to the first febrile port the importance of this factor troversial. Studies of patients who over the height of the fever. Theseizure, whose parent(s) or sibling(s) have CPS and a history of prolongedhad a history of afebrile seizures, seizure may be of any type, but the febrile convulsions in early child- most common is tonic-clonic. Ini-and who had a complex first febrile hood show an increase in mesialseizure (Table 3). Of the 60% of tially there may be a cry, followed by temporal sclerosis. Although there loss of consciousness and muscularchildren who had febrile seizures in may be an association betweenthe NCPP and none of these risk rigidity. During this tonic phase, febrile convulsions that are pro- there may be apnea and incontinence.factors, 2% developed at least one longed or focal and later CPS, a This is followed by the clonic phaseafebrile seizure by age 7 years. Of causal relationship has not been of repetitive, rhythmic jerking move-the 34% who had one risk factor, proven. Only a very small percent- ments and then by post- ictal lethargy3% developed one or more afebrile age of children who have febrile or sleep.seizures, and if two or more risk seizures develop CPS, and it may be Other seizure types may occur,factors were present, the afebrile that the child who is neurologically such as staring with stiffness or limp-seizure rate increased to 13%. A at risk is more likely to have both ness, jerking movements withoutprior neurologic abnormality identi- febrile and complex partial seizures. prior stiffening, or only focal stiffnessfied by examination also was associ- or jerking. Most seizures last fewerated with an increased risk for later Pathophysiology: Etiology than 6 minutes; fewer than 8% lastafebrile seizures, but there was no Most febrile illnesses associated longer than 15 minutes. Thus, theincreased risk from having had mul- with febrile seizures are due to com- child who has a febrile seizure usu-tiple episodes of febrile seizures. mon infections such as tonsillitis, ally is not brought to medical atten- upper respiratory infections, and oti- tion until after the seizure has ended.6 Pediatrics in Review Vol. 18. No. 1 January 1997 Downloaded from http://pedsinreview.aappublications.org/ at Dahlgren Medical Library on January 9, 2012
  • 4. NEUROLOGY Febrile Seizures When a child is seen following a nance imaging (MRI) are seldom A written handout is usually help-febrile convulsion, it is important to helpful and should not be performed ful. The following points should beidentify whether there is an underly- routinely. The electroencephalogram stressed:ing illness requiring treatment. A (EEG) has not been shown to be 1. Although febrile seizures arehistory should include inquiries as to helpful in the evaluation of febrile frightening, they do not causesymptoms of infectious illness, med- seizures. An EEG obtained up to brain damage, and the likelihoodication exposure, trauma, develop- 1 week after a febrile seizure may of developing epilepsy or recur-mental level, and family history of show an abnormality, usually con- rent nonfebrile seizures is veryfebrile or afebrile seizures. A com- sisting of occipital slowing. small.plete description of the seizure Although there is a higher incidence 2. There is, however, a risk of fur-should be obtained from an eyewit- of EEG abnormalities in children ther febrile seizures during theness. In the physical examination, who have febrile seizures, which current or subsequent febrilethe level of consciousness, the increases with age, the EEG does illnesses.presence of meningismus or a tense not help predict recurrences or risk 3. If another seizure occurs, stayor bulging fontanelle or of Kernig for later epilepsy. calm, place the child on his oror Brudzinski sign, and any abnor- her side or abdomen with themalities or focal differences in face downward; do not force any- HOSPITALIZATIONmuscle strength or tone should be thing between the teeth andnoted carefully and reassessed The decision to admit the child who observe the child carefully. If theperiodically. has experienced a febrile seizure for seizure does not stop after Other causes of seizures associ- overnight observation in the hospital 10 minutes, the child should beated with fever must be ruled out, depends on the specific clinical situ- brought to the nearest medicalespecially encephalitis or meningitis. ation and the family circumstances. facility by car or ambulance.A lumbar puncture (LP) is indicated The child should be kept in theif there is any clinical suspicion ofmeningitis. The presence of a source Routine laboratory studies are not indicated (for patientsof infection such as otitis media who have febrile seizures) and should be performed onlydoes not rule out meningitis, and ifthe infant has been taking antibi- as part of the evaluation for a source of fever.otics, partially treated meningitisshould be suspected and an LP per- emergency department holding area Vigorous control of fever byformed. or doctor’s office for at least several antipyretics and sponging often is Typical clinical signs of meningi- hours and re-evaluated. Most chil- advocated but has not been proventis may be absent in those younger dren will have improved and be to lower the risk of febrile seizuresthan 12 to 18 months of age. In gen- alert, and if the cause of the fever recurring. Often, seizures occur aseral, the threshold for performing an has been diagnosed and treated the first sign of a febrile illness.LP should be low, and it should not appropriately, they may be sent Lowering fevers by appropriate usebe omitted on the sole basis of age, home. However, follow-up care of antipyretics such as aceta-family history, or previous number must be assured. If the child’s clini- minophen usually will make theof febrile seizures. If increased cal situation remains unstable, if child more comfortable. However,intracranial pressure is suspected, there is any question of possible some authors have suggested thatthe decision to perform an LP must meningitis, or if parents seem unreli- antipyretics may prolong viral shed-be made by an experienced physi- able or unable to cope, hospitaliza- ding and impair the body’s ability tocian who will weigh the risk of tion is advisable. About 16% of chil- respond to viral infection.delaying a diagnosis of meningitis dren may experience another seizure Questions often arise regardingagainst the risk of an LP. within 24 hours, but it is not known continuation of routine childhood Other causes of seizures associ- how to predict in which cases immunizations. Studies have indi-ated with fever other than meningitis seizures may recur immediately. cated that seizures following child-or encephalitis include infections hood immunizations are no differentsuch as roseola infantum and PARENTAL COUNSELING from other febrile seizures. SeizuresShigella gastroenteritis; certain tox- Febrile seizures are very frightening may occur most commonly follow-ins or drug exposures, including events, and it is not uncommon for ing a pertussis or DPT immunizationdiphenhydramine, tricyclic antide- parents to state that they believed because the pertussis componentpressants, amphetamines, and that their child was dying during the commonly provokes a fever. In eachcocaine; and dehydration causing seizure. They first must be reassured child, the advantages conferred byelectrolyte imbalances. and then given instructions on the vaccines must be weighed against Routine laboratory studies are not management of possible recurrences. the risk, and if immunization isindicated and should be performed Information and counseling should postponed, the situation must be re-only as part of the evaluation for a be provided after the acute event evaluated at each subsequent visit.source of fever. Skull radiographs and at a later time, when parents The period of greatest risk forand neuroimaging such as computed have had a chance to formulate febrile seizure recurrences is up totomography (CT) or magnetic reso- questions. 48 hours following a DPT immu-Pediatrics in Review Vol. 18 No. 1 January 1997 7 Downloaded from http://pedsinreview.aappublications.org/ at Dahlgren Medical Library on January 9, 2012
  • 5. NEUROLOGY Febrile Seizuresnization and 7 to 10 days after a 1 mg/kg per day when the child is been shown to be both completelymeasles immunization. ill or feverish. If side effects of safe and effective. Fortunately, the lethargy or ataxia occur, the dosage majority of children who haveLONG-TERM MANAGEMENT should be halved, and the physician febrile seizures will require no treat-The approach to long-term manage- must evaluate whether the lethargy ment other than parental reassurancement should focus on decreasing could be masking an underlying ill- and will have a good outcome.parental anxiety. Whether prophy- ness such as meningitis. Diazepamlaxis with medication is effective is in both oral and rectal forms has SUGGESTED READINGcontroversial. Side effects occur, and been used successfully in countries Berg AT, Shinnar S, Hauser WA, et al. Aantipyretics alone have not been outside of the United States. prospective study of recurrent febrileshown to be effective in preventing seizures. N Engl J Med. 1992;327: 1122–1127febrile seizure recurrences. There is Conclusion and Prognosis Farwell JR, Lee YJ, Hirtz DG, et al. Pheno-no evidence that the treatment to barbital for febrile seizures: effects on intel- Febrile seizures now are recognized ligence and seizure recurrence. N Engl Jprevent recurrences can prevent thesubsequent development of epilepsy. as a benign syndrome determined Med. 1990;322:364–369 largely by genetic factors, manifested McKinlay I, Newton R. Intention to treat Diazepam and phenobarbital have febrile convulsions with rectal diazepam,been used to prevent recurrences of by an age-related susceptibility to valproate, or phenobarbitone. Dev Medfebrile seizures, although not all seizures that eventually is outgrown. Child Neurol. 1989;31:617–625 Although febrile seizures are Nelson KB, Ellenberg JH. Prognosis in chil-studies have confirmed their effi- dren with febrile seizures. Pediatrics.cacy. Prescription of prophylaxis extremely frightening to parents, 1978;61:720–727should be reserved only for the rare children almost always do quite well. Nelson KB, Ellenberg JH, eds. Consensus Only a small minority will develop Statement on Febrile Seizures: Febrilecases in which multiple seizures Seizures. New York, NY: Raven Press;have occurred in a child who still is epilepsy or recurrent nonfebrile 1981:301very young, there has been focal seizures later. Unless seizures are Offringa M, Patrick M, Bossuyt M, et al. exceedingly long, there is no evi- Risk factors for seizure recurrence in chil-paralysis following a seizure, or the dren with febrile seizures: a pooled analysisparents’ anxiety level remains very dence of risk of brain damage, and of individual patient data from five studies.high even after reassurance. large studies have documented the J Pediatr. 1994;124:574–584 lack of later intellectual and motor Rantala H, Uhari M. Risk factors for recur- Diazepam has been administered rences of febrile convulsions. Acta Neurolorally and rectally to prevent recur- handicap as a result of febrile Scand. 1994;90:207–210rences only during a febrile illness. seizures. Rosman NP, Colton T, Labazzo J, et al. A Long-term management of febrile controlled trial of diazepam administeredPhenobarbital 5 mg/kg per day has during febrile illnesses to prevent recur-been given continuously in a daily seizures should focus on decreasing rence of febrile seizures. N Engl J Med.or twice-daily dosage. There are parental anxiety. Treatment to pre- 1993;326:79–84 vent recurrences has not been shown Stenklyft PH, Carmona M. Febrile seizures.significant drawbacks to both treat- Emerg Med Clin North Am. 1994;12:989ments; diazepam may cause ataxia to prevent the later development of Verity CM, Butler NR, Golding J. Febrileand lethargy, and phenobarbital epilepsy. Treatment to prevent recur- convulsions in a national cohort followed-may cause behavior problems and rences should be recommended in up from birth. I. Prevalence and recurrence in the first five years of life. Br Med J.affect intellectual performance only a small minority of children 1985;290:1307–1310adversely. who have febrile seizures. Potential Verity CM, Butler NR, Golding J. Febrile If treatment is prescribed, oral risks of anticonvulsant therapy convulsions in a national cohort followed- up from birth. II. Medical history and intel-diazepam is preferable and may be should be weighed against benefits. lectual ability at 5 years of age. Br Med J.given in three divided doses to total No currently available treatment has 1985;290:1311–13158 Pediatrics in Review Vol. 18. No. 1 January 1997 Downloaded from http://pedsinreview.aappublications.org/ at Dahlgren Medical Library on January 9, 2012
  • 6. NEUROLOGY Febrile Seizures PIR QUIZ 1. Which one of the following state- A. A complex first febrile seizure. of the brain. ments about recurrence of febrile B. A history of febrile seizures in E. Serum electrolyte levels. seizures is true? the family. A. A complex first febrile seizure C. Female gender. 4. Which one of the following state- is more likely to recur than a D. Multiple episodes of febrile ments about the management of a simple febrile seizure. seizures. child who has had a febrile seizure B. A first febrile seizure occurring E. Younger age of onset of first is true? at 6 months of age is more febrile seizure. A. Continuous phenobarbital pro- likely to recur than one occur- phylaxis will prevent develop- 3. A 6-month-old child who has a ment of epilepsy in subsequent ring at 3 years of age. history of fever of 2 days’ duration years. C. A first febrile seizure with presents with generalized tonic- B. Immunization with diphtheria- fever of 104˚F (40˚C) is more clonic seizures lasting approxi- pertussis-tetanus (DPT) should likely to recur than one with mately 10 minutes. Physical be carried out using half the fever of 101˚F (38.3˚C). examination reveals a rectal standard dose. D. Girls are more likely than boys temperature of 103˚F (39.4˚C), C. Management should be guided to have recurrence of febrile slightly bulging fontanelle, bilat- by serial electroencephalo- seizures. eral otitis media, and lethargy. graphic studies. E. Longer duration of fever The infant is arousable but irrita- D. Parents should be reassured before the initial febrile seizure ble. Which one of the following of the benign nature of febrile is a risk factor for recurrence is the most appropriate initial seizures and given instructions compared with shorter duration diagnostic test? for handling a possible of fever. A. Computed tomographic scan recurrence. 2. Which one of the following is the of the head. E. Use of antipyretics at the first most important risk factor for B. Electroencephalography. sign of fever has been shown developing epilepsy following C. Lumbar puncture. to decrease the recurrence of febrile seizures? D. Magnetic resonance imaging febrile seizures. Earning CME Credit-Completing the PIR Quiz The American Academy of Pediatrics 1997 PIR will be awarded for up to activities, including AAP Spring (AAP) is accredited by the Accredita- 2 years. Credits will be posted to the Session or Annual Meeting, tion Council for Continuing Medical year in which they are submitted. AAP CME courses, ACQIP, Pedi- Education (ACCME) to sponsor con- Verification of Credit will be atric UPDATE Audiocassette Tape tinuing medical education for physi- mailed by: April 30, 1998. You will Program, or other AAP-approved cians. Pediatrics in Review (PIR) was receive a complimentary transcript by courses. planned and produced in accordance April 30, 1998, containing a sum- Other Organizations Granting with the ACCME Essentials. mary of CME credits earned in 1997 Credit: PIR has been approved for The AAP designates this activity through AAP programs. If you credit as follows: for up to 38 hours in Category 1 of require a transcript at any other time • American Academy of Pediatrics the Physician’s Recognition Award of of the year, there will be a fee of $25 (AAP): up to 38 hours of credit the American Medical Association for processing. toward the AAP PREP Education (3 hours per completed print issue of Mail form to: American Academy Award PIR and 2 hours per completed com- of Pediatrics - PREP Office, 141 • American Osteopathic Association pact disc issue of PIR). Northwest Point Boulevard, PO Box (AOA): up to 12 hours, Category PIR Quiz: A short quiz can be 927, Elk Grove Village, IL 60009- 2-B found at the end of each article in 0927 • National Association of Pediatric PIR. Use the PIR Quiz Card (bound PREP Education Award: The Nurse Associates and Practitioners into the January issue) to record your AAP PREP Education Award recog- (NAPNAP): up to 38 contact answers. Each question has a single nizes Academy Fellows and Candi- hours. best answer. The answers to the ques- date Fellows who earn a minimum of • Canadian Paediatric Society has tions appear on the inside front cover 150 AAP-approved CME credits over approved PREP as one method for of each issue. 3 consecutive years. The Award will pediatricians to demonstrate main- 1997 Credit Deadline: February be mailed July 1998 to all individuals tenance of competence 28, 1998. If you want to receive who qualify. To qualify for the PREP (MOCOMP) CME credit in 1997, the PIR Quiz Education Award, an Academy Fel- • PREP has been reviewed and Card must be received in the PREP low or Candidate Fellow must: accepted by the American Acad- Office by February 28, 1998. Credit • Earn a minimum of 75 credit emy of Family Physicians (AAFP) reply material received after February hours through participation in for up to 38 Prescribed hours. 28, 1998, will be applied to the fol- PREP or PREP: The Course, and Term of approval begins January lowing year. • Earn the remaining credit hours 1997. Enduring materials are Expiration of Credit: December (75 hours) through other Acade- approved for 1 year with the 31, 1999. Credit for completing the my-sponsored or -approved CME option to request renewal.Pediatrics in Review Vol. 18 No. 1 January 1997 9 Downloaded from http://pedsinreview.aappublications.org/ at Dahlgren Medical Library on January 9, 2012
  • 7. Febrile Seizures Deborah G. Hirtz Pediatrics in Review 1997;18;5 DOI: 10.1542/pir.18-1-5Updated Information & including high resolution figures, can be found at:Services http://pedsinreview.aappublications.org/content/18/1/5References This article cites 8 articles, 1 of which you can access for free at: http://pedsinreview.aappublications.org/content/18/1/5#BIBLSubspecialty Collections This article, along with others on similar topics, appears in the following collection(s): Neurologic Disorders http://pedsinreview.aappublications.org/cgi/collection/neurolo gic_disordersPermissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: /site/misc/Permissions.xhtmlReprints Information about ordering reprints can be found online: /site/misc/reprints.xhtml Downloaded from http://pedsinreview.aappublications.org/ at Dahlgren Medical Library on January 9, 2012

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