Indian Pediatrics - Febrile Seizure

8/17/2019 Indian Pediatrics - Febrile Seizure

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Indian Pediatrics 2001; 38: 733-740

Febrile Seizures

Pratibha D. Singhi, M. Srinivas

From the Division of Pediatric Neurology and Neuro Developmental Unit, Department of Pediatrics,PGIMER, Chandigarh 160 012, India.Correspondece to: Dr. Pratibha D. Singhi, Chief, Neurology and Neuro Developmental Unit, Department of Pediatrics, PGIMER, Chandigarh 160 012, India.E-mail: [email protected]

Febrile seizures are the most frequent neurologic disorder in children. There have been a number of controversies regarding their management, recurrence risk and long term outcome. Recently the American

Academy of Pediatrics (AAP) has set guidelines for management of simple febrile seizures in childhood(l).

This article provides an update on the current status and management practices of febrile seizures.

Definitions

Febrile seizures are defined as an event in neurologically healthy infants and children between 6 monthsand 5 years of age, associated with fever >38ºC rectal temperature but without evidence of intracranialinfection as a defined cause and with no history of prior afebrile seizures(2). Febrile seizures are to bedistinguished from epilepsy which is characterized by recurrent nonfebrile seizures. All seizures with fever are not febrile seizures. Convulsions in children with fever due to pyogenic meningitis, hypernatremicdehydra-tion or other metabolic disorders are not included. Generally, febrile seizures occur during earlyphase of rising temperature and are uncommon after 24 hours of onset of fever(3).

Simple febrile seizures are generalized seizures, lasting less than 15 min, not recurring within 24 hours, and

with no postictal neuro-logical abnormalities.

Complex febrile seizures are focal, prolonged or recurrent within 24 hours or associated with postictalneurological abnor-malities including Todd paresis. These seizures constitute around 15% of febrileseizures.

Febrile status is seizure duration of 30 min. or more, either one long lasting or a series of shorter seizureswithout regaining conscious-ness interictally.

Incidence

Febrile seizures occur in 3-4% of children under the age of 5 years(3). Usually, they do not occur beyond

the age of 5 years implying a specific vulnerability of young children to fever as a precipitant. The mediumage of occurrence is 18-22 months(4).

It has been recognized that there is significant genetic component for suscepti-bility to febrile seizures. Twoputative febrile seizure (FS) loci, FEB1 (chromosome 8q13-q2l) and FEB2 (chromosome 19P) have beenmapped. Furthermore, a mutation in the voltage gated sodium (Na+) channel beta subunit gene (SCN1B) atchromosome 19ql3.1 was identified in a family with clinical subset, termed generalized epilepsy with febrileseizures plus syndrome (GE FS(+)). Studies have also linked the susceptibility of febrile seizures to a geneon chromosome 5ql4-ql5 (FEB4)(5). The risk of another child having febrile seizure is one in five with oneaffected sibling and one in three if both parents and a previous child have had febrile seizures(6).

Risk Factors for Recurrence of Febrile Seizures

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The determinants for recurrent febrile seizures and for later epilepsy are different. The average recurrencerate after a first febrile seizure is 30-40% but this is dependent on complex interplay between the geneticand environmental factors. Recurrence risk is related to various risk factors, which may include the type of treatment. One study found a total of five risk factors for recurrent febrile seizures when no prophylaxis wasgiven(7). In order of predictive power it included young age at onset (


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Type of Epilepsy

Different types of seizures (generalized tonic clonic, absence, complex partial) may occur in those childrenwho develop epilepsy after previous febrile seizures. In rare cases multiple febrile recurrences are followedby severe myoclonic epilepsy(16). Contrary to earlier belief, only a small proportion of children with febrileseizures go on to develop temporal lobe epilepsy(17). The relationship between febrile seizures inchildhood, complex partial seizures, temporal lobe epilepsy and mesial temporal sclerosis in particular haslong been assumed based upon associations seen among these and other factors in adults as well aschildren, largely with refractory epilepsy. While one study had shown strong association between prior febrile seizures and temporal but not extra temporal lobe epilepsy(14) another noted that there is noevidence that prior febrile seizures were associated with complex partial seizures, localization-relatedepilepsy, or specifically with temporal lobe epilepsy or with hippocampal atrophy or other potentially relatedfindings in the temporal lobe(18). In selected families, prolonged febrile seizures were found to have astrong association with temporal lobe epilepsy(19). Thus, the relation-ship between febrile seizures andmesial temporal sclerosis is till date inconclusive. Mesial temporal sclerosis has been reported both beforeand after febrile seizures. There is evidence demonstrating that mesial temporal sclerosis is both a resultand a cause of seizures(20).

Intellectual and Motor Functions

There is no evidence that simple febrile seizures cause any structural damage to the brain or that children

with simple febrile seizures are at risk for cognitive decline. Population based studies have shown thatfebrile seizures in early childhood do not have adverse effects on behavior, scholastic performance andneurocognitive attention(21).

Management of a Child With Febrile Seizure

(a) During the Seizure

Any child with a febrile seizure needs to be managed as for any other seizure, with airwaymanagement, a semi prone position to decrease the risk of aspiration, monitoring of vitalsigns and other supportive care. Seizure should be terminated with IV diazepam or lorazepam. Rectal diazepam (0.5 mg/kg) has also been found to be safe and effective. It iscompletely absorbed and anticonvulsant plasma concen-trations are obtained within 2-4 min.,

almost as rapidly as an intravenous dose. Where ready rectal preparations are not available,the undiluted intravenous preparation is sucked in a small syringe and given through aPolythene tube which is gently inserted 4 to 5 cm into the anus after lubricating withlignocaine jelly. This method has been found to be effective in acute seizure control in febrileand afebrile seizures at home and in a hospital setting(22).

Rectal, oral or IV lorazepam(23), rectal clonazepam(24), nasal midazolam(25) and other drugshave also been used in acute seizure control but to a lesser extent. Lora-zepam appears tobe as effective as diazepam in seizure control and has a more protracted duration of action.In a preliminary study, midazolam by nasal route demonstrated effective seizure control inchildren with epilepsy(25). Recent studies have shown that midazolam (0.2 mg/kg) givenintranasally is as safe and as effective as diazepam given intravenously in the management

of febrile seizures in children(26).

(b) Hospitalization

The decision to admit should be individualized but admission is usually not necessary. Mostchildren should be observed until they are awake and alert. Children, especially those with afirst febrile seizure, should be hospitalized if any of the following are present: (i ) Lethargybeyond postictal state; (ii ) Unstable clinical status; (iii ) Age


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The investigations are oriented towards finding the cause of fever and to rule out meningitis.Fever is most often due to viral infections of upper respiratory tract, acute otitis media,infections of urinary tract, gastrointestinal tract and febrile reactions after vaccinations(27). Agood clinical examination is necessary to determine the focus of fever, and investigationswould be indicated accordingly. Serum electrolytes, blood glucose, calcium, magnesium andblood counts are not routinely needed.

(d) Lumbar Puncture (LP)

LP is not routinely performed in children with fever and first seizure. It is however, indicatedwhenever a doubt of meningitis exists. Risk factors for meningitis in patients presenting withfever and seizure are(28): (i ) Abnormal neurological examination, especially meningeal signs;(ii ) Focal seizure, suspicious physical findings (rash or petechiae, cyanosis, hypotension,grunt, etc.; (iii) A physician seen within 48 hours of fever; and ( iv ) Ongoing seizure activity atthe time of arrival in the hospital. Used in combination, these risk factors are very helpful inidentifying children with meningitis and their negative predictive value was 100%(28).

The AAP strongly recommends LP in patients under 12 months of age presenting with fever and seizure because meningeal signs may be minimal or absent in this age group. LP is to beconsidered in patients 12 to 18 months of age(29) as symptoms and signs of meningitis maybe subtle. Symptoms and signs of meninigitis may also be masked in children with febrileseizures who have received antibiotics, hence LP is warranted in such cases also(29). The

spinal fluid findings may be normal in early meningitis thus a negative spinal tap does noteliminate the need for careful follow up.

(e)EEG

An EEG is not necessary in the routine evaluation of a child with a first simple febrile seizure.The reported incidence of paroxysmal EEG abnormalities in children with FS vary widely from2 to 86%. The first reason for this variability is related to differences used for subjectselection by different authors. Second the criteria used in different studies to defineparoxysmal discharges are different. Some authors don’t confine their definition of paroxysmal activity to spikes or spike waves and include phantom spike waves, high voltageslow waves burst and so on. Third the timing of EEG has to be taken into consideration asgenerally detection of epileptic discharges is unusual within the first postictal week and is

also difficult in early childhood before the age of 3 years(30).

Abnormal EEGs do not reliably predict the development of epilepsy or recurrence of febrileseizures. Considering the wide variability and the poor prediction, EEG has no role in themanagement of a patient with simple febrile seizure. The yield of postictal EEG in childrenwith complex febrile seizures is low, and similar to that in children with simple febrileseizures. Routine EEG in neurologically normal children with complex febrile seizures is notindicated(31).

(f) Neuroimaging

Neither CT nor MRI head has any role in the management of a child with simple febrile

seizure.

(g) Treatment of Fever

Antipyretics are not effective in preventing recurrent febrile seizures, but are useful in makingthe child more comfortable(32).

Long Term Management

The primary goal of long-term manage-ment of febrile seizure is to prevent recurrences. Treatment optionsinclude: (a) prolonged daily prophylaxis with phenobarbi-tone or valproate; and (b) intermittent prophylaxiswith diazepam or other benzo-diazepines.


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Continuous Prophylaxis

Phenobarbital is effective in preventing the recurrence of simple febrile seizures(33). In a controlled doubleblind study, daily therapy with Phenobarbital reduced the rate of subsequent febrile seizure from 25 per 100subjects/years to 5 per 100 subjects/year(34). The adverse effects include behavioral problems such ashyperactivity and hyper-sensitivity reactions. Long-term phenobarbital treatment appears to influencecognition and behavior, a large price for prevention of benign condition.

Valproate is as effective as phenobarbitone in preventing recurrent, simple febrile seizures. In randomized,controlled studies, only 4% of children taking valproate as opposed to 35% of control subjects had asubsequent febrile seizure(35). Drawbacks to therapy with valproate include its rare association with fatalhepatotoxicity, thrombocytopenia, weight loss and gain, gastrointestinal disturbances and pancreatitis.

Neither Phenobarbital or Valproate is effective in reducing the risk of epilepsy in children with febrileseizure.

Intermittent Diazepam Prophylaxis

Diazepam administered intermittently either rectally as suppositories, or solution or orally at the onset of fever has been shown to be effective in preventing recurrence of febrile seizures(36). By either route,generally a dose of 0.3 to 0.5 mg/kg (max 10 mg) is used and repeated every 8-12 hours if temperature is38ºC or more. A maximum of 4-5 doses are given per illness. Intermittent clobazam (1mg/kg/day) given

orally has also been found to be useful in preventing febrile seizure recur-rences(37). A potential drawbackto inter-mittent medication is that seizure could occur before fever is noticed. Adverse effects of oraldiazepam include lethargy, drowsiness and ataxia(36). The sedation associated with this therapy couldmask evolving signs of meningitis. It must however be remembered that this therapy does not decrease theincidence of later epilepsy in children with febrile seizures(38).

Patient Education

This perhaps is the most important (and often neglected) aspect of management of febrile seizures. Asseizures in their child can be very frightening for the parents they should be counselled properly withparticular emphasis on: (i ) The benign nature of the febrile seizures; ( ii ) That febrile seizures do not lead toneurological problems or develop-mental delay; (iii ) What they should do immediately if their child hasanother seizure; (iv ) A doctor should be consulted if the seizure lasts for more than 15 min. or if the post

ictal drowsiness persists for more than 30 min.

Conclusions

Febrile seizures in children are benign events that do not have any long term neurological sequalae, andneither long term daily phenobarbitone nor intermittent diazepam have any role in the management of thesechildren with simple febrile seizures(39). Appropriate education and emotional support should be provided toparents. In situations where severe parental anxiety is associated with febrile seizures, intermittent therapymay be advised; continuous antiepileptic therapy is rarely used. Recent epidemiologic studies have alsoconfirmed that the vast majority of children with febrile seizures have a benign prognosis and a normal longterm outcome(40,41).

Contributors: PD conceptualized and drafted the manuscript, she will act as the guarantor. SM helped inliterature review and drafting.

Funding: None.Competing interests: None stated.

Key Messages

Febrile Seizures are generally benign events and do not cause lasting intellectual or

neurologic damage.

EEG and neuroimaging are not indicated in the usual evaluation of febrile seizure.


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Anti-epileptic therapy (Phenobarbitone/Valproate), either intermittent or continuous, can

prevent recurrences of febrile seizure but does not prevent subsequent epilepsy.

Most children with febrile seizures do not require anti-epileptic therapy; in cases of severe

parental anxiety and/or multiple recurrences, intermittent therapy may be advised.

References

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2. Consensus Development Panels. Febrile seizures: Long-term management of children withfever associated seizures. Pediatrics 1980; 66: 1009-1012.

3. Aicardi J. Febrile convulsions. In: Epilepsy in Children: International Review of ChildNeurology Series. New York, Raven Press, 1994; pp 253-275.

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5. Nakayan J, Hassano K, Iwasaki N. Significant evidence for the linkage of febrile seizuresto chromosome 5 ql4-ql5. Hum Mol Gene 2000; 9: 87-91.

6. Baraitser M. Relevance of a family history of seizures. Arch Dis Child 1983; 58: 404-405.

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9. El Radhi AS, Banejeh S. Effect of fever on recurrence rate of febrile convulsions. Arch DisChild 1989; 64: 869-870.

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factors for seizure recurrence in children with febrile seizures: A pooled analysis of individualpatient data from five studies. J Pediatr 1994; 124: 574-584.

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15. Berg AT, Shinnar S. The contributors of epilepsy to the understanding of childhoodseizures and epilepsy. J Child Neurol 1994; 9 (suppl): 2Sl9-2S26.

16. O’Donohoe NV. Febrile convulsions. In: Driefuss FE, Paret E, Wolf P. EpilepticSyndromes in Infancy. Childhood and Adolescence. Eds. Roger J, Bureau M, Dravet C,London, John Libbey, 1992; pp 45-52.

17. Knudson FU. Febrile seizures: Treatment and prognosis. Epilepsia 2000; 41: 2-9.

18. Berg AT, Shinner S, Levy SR, Testa FM. Childhood onset epilepsy with and without febrileseizures. Neurology 1991; 53: 1742-1748.

19. Maher J, McLachlan RS. Febrile convulsions: Is seizure duration the most importantpredictor of temporal lobe epilepsy? Brain 1995; 118: 1521-1528.

20. Liv Z, Mikate M, Holmes GL. Mesial temporal sclerosis: Pathogenesis and significance.Pediatr Neurol 1995; 12: 5-16.

21. Verity CM, Greenwood R, Golding J. Long term intellectual and behavioral outcomes of children with febrile convulsions. N Engl J Med 1998; 338: 1723-1725.

22. Knudsen FU. Rectal administration of diazepam in solution in the acute treatment of convulsions in infants and children. Arch Dis Child 1979; 54: 855-857.

23. Giang DW, Mc Bride MC. Lorazepam versus diazepam for the treatment of statusepilepticus. Pediatr Neurol 1988; 4: 358-361.

24. Rylance GW, Poulten J, Cheery RC. Willen RE. Plasma concentrations of clonazepamafter single rectal administration. Arch Dis Child 1986; 61: 186-188.

25. O’Regan ME, Brown JK, Clark M. Nasal rather than rectal benzodiazepines in themanagement of acute childhood seizures. Dev Med Child Neuro 1996; 38: 1037-1045.

26. Lahat E, Goldman M, Burr J, Bistritzer T, Berkovitch M. Comparison of intranasalmidazolam with intravenous diazepam for treating febrile seizures in children: A prospectiverandomized study. BMJ 2000; 321: 83-86.

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30. Yamatogi Y, Ohtahara S. EEG in febrile convulsions. Am J EEG Technol 1990; 30: 267-280.

31. Maytal J, Steele R, Eviate L, Novak G. The value of postictal EEG in children withcomplex febrile seizures. Epilepsia 2000; 41: 219-228.

32. Uhari M, Rantala H, Vainionpaa L, Kurttila R. Effect of acetaminophen and of low inter-mittent doses of diazepam in prevention of febrile seizures. J Pediatr 1995; 126: 991-995.

33. Kohrman MH, Hayes MS, Kerr SL, Langas TJ, Cohen ME. Phenobarbital for febrileseizures. N Engl J Med 1990; 323: 484.

34. Camfield RR, Camfield CS, Shapiro SH, Cumming C. The first febrile seizure anti-pyreticinstruction plus either Phenobarbital or placebo to prevent recurrence. J Pediatr 1980; 97: 16-21.

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36. Rosman NP, Colten T, Labazz P, Gilbert PL, Gasdella NB, Kaye FM et al. A controlledtrial of diazepam administered during febrile illnesses to prevent recurrence of febrileseizures. N Engl J Med 1993; 329: 79-84.

37. Manreza ML , Gherpelli JL, Machado Hairtel LR, Pedreira CC, Heise CO, Diament A.Treatment of febrile seizures with intermittent clobazam. Arq Neuropsiquiatr 1997; 55: 757-761.

38. Knudson FU, Paerregaard A, Anderson R, Anderson J. Long term outcome of prophy-laxisfor febrile convulsions. Arch Dis Child 1996; 74: 13-18.

39. Baumamm RJ, Dufner PK. Treatment of children with simple febrile seizures. The AAPpractice parameter. Pediatr Neurol 2000; 23: 11-17.

40. Verity CM, Golding J. Risk of epilepsy after febrile convulsions: A National Cohort Study.BMJ 1991; 303: 1373-1376.

41. Annegers JF, Hauser WA, Sherts SB, Kurland LT. Factors prognostic of unprovokedseizures after febrile convulsions. N Engl J Med 1987; 316: 493-498 .

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Indian Pediatrics - Febrile Seizure

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