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Chapter 60 EVALUATION OF FEVER IN CHILDREN YOUNGER THAN AGE THREE418

7. Which antipyretics work best for children?

Studies show that acetaminophen (15 mg/kg) and ibuprofen (10 mg/kg) have similar efﬁcacy,

and both work well for getting febrile children to defervesce.

Note: Most children’s elixirs contain half the amount of an adult tablet per teaspoon (5 mL).

For example, an adult tablet of ibuprofen contains 200 mg, whereas the children’s elixir

contains 100 mg/5 mL.

8. What is the most common cause of antipyretic failure?

Underdosing, either by dose or by schedule. Parents may not know the child’s weight, fail to

calculate an appropriate dose, or be unfamiliar with units of measure (such as a teaspoon).

It is also common for parents to believe that antipyretics should cure the fever, and they may

complain, “I gave her the medicine and it helped for a while, but the fever just came right

back.” Parental education and provision of an oral syringe frequently help with this issue.

9. What is wrong with baby aspirin; it is for babies, right?

Aspirin administration to children with viral infections has been associated with Reye’s

syndrome (encephalopathy and acute liver failure). This syndrome, although rare, carries a

high mortality rate (20% to 40%). Although some pediatric conditions (such as juvenile

rheumatoid arthritis and Kawasaki disease) may involve treatment with aspirin, its use in

children with fever of unclear etiology should be strictly avoided.

10. Is there any good reason not to treat a fever?

No. Children with fever feel crummy, feed poorly, and worry their caregivers; the quickest way

to make them feel better is to bring the fever down.

11. What are febrile seizures?

Febrile seizures are the most common seizure disorder seen in children (incidence 4%) and

are typically associated with high fevers. There has been a great deal of discussion about

whether these seizures are associated with rate of rise, rather than absolute temperature, but

there is no evidence to support this theory. There is no increased risk of SBI in patients with

simple febrile seizures as compared to children who present with fever alone. A simple febrile

seizure is characterized as a generalized tonic clonic seizure that does not recur in a 24-hour

period, is associated with fever, lasts longer than 15 minutes, and occurs in an otherwise

neurologically normal child between the ages of 3 months and 5 years. There is excellent

long-term data that shows no effect on cognitive development or intelligence. Although

benign, simple febrile seizures are very frightening for parents.

12. Does careful administration of antipyretics prevent recurrence of febrile

seizures?

No. Placebo-controlled trials with antipyretics show no difference in recurrence rates during

subsequent febrile illnesses. About one third of patients will have a second febrile seizure.

Risk factors for recurrence include family history, age (younger age at presentation more likely

to recur), and height of temperature (lower temperature at presentation more likely to recur).

Studies also show no beneﬁt to diazepam prophylaxis to prevent recurrence in patients with

simple febrile seizures during subsequent febrile illnesses.

13. How should tiny babies with fever be evaluated?

Febrile infants (temperature of 38.0°C) younger than 1 month should receive a full sepsis

work-up:

Urinalysis and culture (by catheterization or suprapubic aspiration)

Complete blood count and culture

Lumbar puncture (LP)

Chest radiograph (only with respiratory symptoms)

Stool analysis for white blood cell (WBC) count and culture (if there is a history of diarrhea)

Infants should receive intravenous (IV) antibiotics and be admitted to the hospital.

Chapter 60 EVALUATION OF FEVER IN CHILDREN YOUNGER THAN AGE THREE 419

Note: Age cut-offs for fever evaluation are based on gestational age, not age since birth.

This means that a 32-week premature infant born 6 weeks ago is still considered to be

younger than 1 month.

14. What happens after the magic 1-month mark?

For infants 1 to 3 months of age with a fever without a source, risk stratiﬁcation is

recommended. See algorithm in Figure 60-1.

15. What about older infants and young children?

For children 3 to 36 months with a fever without a source, follow the algorithm in Figure 60-2

(note different temperature cut-off for this older age group).

16. How do we decide when to do a LP in older babies and young children?

A LP should be performed in any child who appears toxic or has signs of meningitis. Be aware

that many of the classic signs of meningitis (e.g., Brudzinski’s sign, Kernig’s sign, neck

stiffness, or bulging fontanelle) are frequently absent and unreliable in young children.

17. What if the child has a fever source or one is found during the work-up?

It depends on the source and the age group. A viral source often makes the risk for

bacteremia and meningitis low. However, a bacterial source may predispose to these entities

and should be strongly considered in patients younger than 3 months of age. If an identiﬁed

source completely explains the clinical presentation, stop looking and treat it. If not, complete

the evaluation as previously described. Be aware that urinary tract infections, and occasionally

bacteremia, may coexist with viral infections respiratory infections such as bronchiolitis and

gastroenteritis.

Figure 60-1. Algorithm for infants 1–3 months of age. Abx, antibiotics; Bcx, blood

culture; CXR, chest X-ray; LP, lumbar puncture; UA, urinalysis; Ucx, urine culture;

WBC, white blood cell count.

Toxic?

Yes

Antipyretics,

Home with 24 hour

recheck and return

precautions

WBC/Bcx

UA/Ucx

IV Abx

ADMIT

Rochester Option

UA/Ucx, WBC/Bcx,

CXR if respiratory sx

(no LP, no Abx)

Philadelphia Option

UA/Ucx, WBC/Bcx, CXR if

respiratory sx, LP

Meets low risk criteria and reliable

caregiver?

Admit, consider

observation without

antibiotics in lower risk

patients with normal urine

and CSF

NoYes

Chapter 60 EVALUATION OF FEVER IN CHILDREN YOUNGER THAN AGE THREE420

18. Must we always follow the guidelines, or is there room for clinical judgment in

there somewhere?

A study of more than 3,000 febrile infants seen by almost 600 pediatricians throughout the United

States demonstrated that selective testing by experienced clinicians in ofﬁce-based practice was

as effective in appropriately identifying and treating SBI as rigid adherence to clinical guidelines.

Their ﬁndings suggest that if close follow-up is feasible, experienced clinicians may use clinical

judgment in select cases rather than published recommendations in their management strategy of

febrile infants. Unfortunately the ED physician may not have the luxury of this close follow-up.

19. What if the child looks great; can he or she go home?

Nontoxic-appearing children older than 1 month who meet low-risk criteria may be discharged

home with return precautions and close follow-up. This, of course, presumes they have a

reliable caregiver, a tenable social situation, and reasonable access to transportation.

20. What are low-risk criteria?

The two sets of low-risk criteria used most often are the Rochester and Philadelphia criteria.

Both presume the child is previously healthy and well appearing at the time of evaluation.

Rochester criteria

WBC between 5,000 and 15,000 with absolute band count (ABC) 5 1,500

Urine WBC , 10/high power ﬁeld (hpf)

Stool WBC ,5/hpf (in infants with diarrhea)

Note: No LP performed

Figure 60-2. Algorithm for children 3–36 months of age. Abx, antibiotics; Bcx,

blood culture; CXR, chest X-ray; LP, lumbar puncture; UA, urinalysis; Ucx, urine

culture; WBC, white blood cell count.

Toxic?

Yes

T ≥39°C?

Yes

Antipyretics,

home with 24 hour

recheck and return

precautions

WBC/Bcx

UA/Ucx

IV Abx

ADMIT

1. UA/Ucx for the following:

All females ≤ 2 years

Circumcised males ≤ 6 months

Uncircumcised males ≤ 12 months

2. CXR if respiratory symptoms

Treat +urine screening test

and +CXR

Home with 24 hour recheck

and return precautions

Chapter 60 EVALUATION OF FEVER IN CHILDREN YOUNGER THAN AGE THREE 421

Philadelphia criteria

WBC , 15,000 with band-to-neutrophil ratio ,0.2

Urine WBC , 10/hpf and no bacteria on Gram stain

Cerebrospinal ﬂuid (CSF) WBC , 8/hpf

Negative CSF Gram stain

Stool and chest radiograph negative (if obtained)

21. What is the risk of occult bacteremia (bacteremia without a focal infection)?

Although occult bacteremia usually resolves spontaneously, it may lead to localized infections

such as meningitis, pneumonia, or osteomyelitis. Evidence gathered since the widespread use

of the heptavalent pneumococcal vaccine suggests that the current rate of occult bacteremia is

less than 1% in well-appearing febrile children between the ages of 3 months to 3 years. This

risk is low enough that routine blood cultures are no longer recommended for children older

than 3 months.

22. What antibiotic should be used for empiric coverage of bacteremia?

Younger than 28 days

Cefotaxime, 50 mg/kg IV (may consider substituting with Gentamicin 2.5 mg/kg

intravenously [IV] in ﬁrst week of life to treat Group B Strep)

plus

Ampicillin, 50 mg/kg IV (to cover for Listeria)

28 days to 3 months

Cefotaxime, 50 mg/kg IV

3 to 36 months

Ceftriaxone 50 mg/kg IV or intramuscularly ([IM] 24-hour dosing) or Cefotaxime, 50 mg/kg IV

23. Which infants should receive acyclovir?

Risk factors for neonatal Herpes simplex virus (HSV) infection include:

Maternal HSV infection at delivery (although two thirds are asymptomatic)

Maternal history of HSV or other sexually transmitted diseases

Vesicular rash

Seizures

CSF pleocytosis (20–100 WBCs is typical)

Patients are usually less than 22 days of age. Patients with risk factors should be started on

acyclovir pending a HSV polymerase chain reaction (PCR) test from the CSF. Clinical judgment

should be used in the decision to discontinue acyclovir given that the initial PCR may be a

false-negative. The dose is 20 mg/kg IV every 8 hours (dose and schedule adjusted for

gestational age and renal impairment).

24. What about children with fever and rapidly progressive petechial rash?

This is disseminated meningococcemia until proved otherwise. Patients with this type of

infection may progress very rapidly. The LP may be deferred until the patient is stable and

should not delay antibiotic administration. Dosages below ensure coverage for invasive,

resistant pneumococcal meningitis which also may cause purpura fulminans.

Cefotaxime, 75 mg/kg IV immediately

Vancomycin, 15 mg/kg IV immediately

WEBSITE

Pediatric febrile seizures. www.emedicine.com/EMERG/ topic376.htm

Chapter 60 EVALUATION OF FEVER IN CHILDREN YOUNGER THAN AGE THREE422

BIBLIOGRAPHY

1. Bachur RG, Harper MB: Predictive model for serious bacterial infections among infants younger than 3 months

of age. Pediatr 108:311–316, 2001.

2. Baraff LJ: Clinical policy for children younger than three years presenting at the emergency department with

fever. Ann Emerg Med 42:546–549, 2003.

3. CDC: Direct and indirect effects of routine vaccination for children with 7-valent pneumococcal conjugate

vaccine on incidence of invasive pneumococcal disease—United States, 1998–2003. MMWR 54(36):893–897,

2005.

4. Gorelick MH, Hoberman A, Kearney D, et al: Validation of a decision rule identifying febrile young girls at high

risk for urinary tract infection. Pediatr Emerg Care 19:162–164, 2003.

5. Kupperman N, Fleisher GR, Jaffe DM: Predictors of occult pneumococcal bacteremia in young febrile children.

Ann Emerg Med 31:679–687, 1998.

6. Pantell RH, Newman TB, Bernzweig J, et al: Management and outcomes of care of fever in early infancy. JAMA

291:1203–1212, 2004.

7. Stoll ML, Rubin LG: Incidence of occult bacteremia among highly febrile young children in the era of the

pneumococcal conjugate vaccine. Arch Pediatr Adolesc Med 158:671–675, 2004.

8. Wilkinson M, Bulloch B, Smith M: Prevalence of bacteremia in children aged 3–36 months presenting to

the emergency department with fever in the post pneumococcal conjugate vaccine era. Acad Emerg Med

16:220–225, 2009.

423

SEIZURES IN INFANCY AND CHILDHOOD

CHAPTER 61

Andrew M. White, MD, PhD

1. How does one determine if an event in a child is actually a seizure?

Many events that appear to be seizures are actually non-epileptic. These events can be

classiﬁed by the age in which the event occurred and are given in Figure 61-1.

Questions helpful in deciding whether an event was or was not a seizure include:

Is the movement suppressible? Seizure movements will continue despite someone holding

a limb. Tics or stereotypies (a repetitive or ritualistic movement, posture, or utterance) are

suppressible.

Is the event distractible? Seizures will continue if you call a person’s name; daydreaming

will not.

Were the movements jerking or thrashing? Typically seizures involve rhythmic jerking and

not thrashing movements or pelvic thrusting. It is always good to have a witness

demonstrate the movements.

Are the events always provoked? Seizures are generally not provoked; breath holding

spells are.

Is there tongue biting during the event and, if so, where? During a true seizure the tongue is

usually bitten on the side. During a nonepileptic spell, the tongue may be bitten on the tip.

Was there urination or loss of stool? This can happen during nonepileptic spells, but this

favors a diagnosis of true seizure.

Does it only happen during exercise? Cardiac events are more likely to occur during exercise.

What do the eyes do during the seizure? During most seizures, the eyes remain open.

Does it happen only during certain times of day? Usually seizures will happen at all times

of day, but there are certain types that are much more frequent in sleep (benign rolandic)

and other that are more frequent during waking hours (benign infantile partial seizures)

Does it only happen upon standing? Likely to be orthostatic syncope.

What is the child like following the event? Except for absence-type seizures, children are

post-ictal following seizures.

Does the child retain consciousness during the event? If it is a generalized tonic-clonic

seizure, this is impossible as both halves of the brain are involved. It is possible for simple

seizures.

Does the child remember the event? Typically the child will not remember the entire

complex partial seizure or any part of a generalized tonic-clonic seizure.

2. What can be explained about the child’s history?

Get a step-by-step description of the events before, during, and following the seizure.

What the child was doing prior to the seizure can help differentiate between seizure and

breath holding.

A good description of the seizure itself, including the manner in which it started and

evolved, how long it lasted (this is usually signiﬁcantly overestimated by the parents), and

what the patient was like after the event are all useful pieces of information.

Additional questions should be asked to try to establish the cause of the seizure. These

include questions with regard to illnesses, trauma, and development. The patients’ past

medical history should be obtained, as well as a family medical history of seizures.

In an epilepsy patient, inquiries about medication compliance are necessary.

Chapter 61 SEIZURES IN INFANCY AND CHILDHOOD424

Figure 61-1. Evaluation of child with simple febrile seizure. CT, computed tomography; EEG, electroen-

cephalogram; MRI, magnetic resonance imaging. (Adapted from Committee on Quality Improvement,

Subcommittee on Febrile Seizures, American Academy of Pediatrics: Practice parameter: the neurodiag-

nostic evaluation of the child with a ﬁrst simple febrile seizure. Pediatrics 97:769–775, 1996. Available

at www.aap.org/policy/neuro.htm.)

Chapter 61 SEIZURES IN INFANCY AND CHILDHOOD 425

If the patient is febrile, the source of the fever should be sought. A careful search for any

evidence of NAT (retinal hemorrhages, bruising, fractures) should be performed.

4. How can I classify a pediatric seizure?

There are several ways in which a seizure can be classiﬁed. The ﬁrst is by its appearance

(focal versus generalized). It is important to identify whether or not the seizure started focally

and then secondarily generalized or whether it started as a generalized seizure. If the seizure is

focal, it is important to obtain an exact description of where it started and if possible, what the

child experienced prior to the seizure. This can help signiﬁcantly in the localization of the

epileptic focus. Seizures can also be classiﬁed by syndrome, prognosis, and cause.

5. What are common reasons for a seizure in the neonate?

The most frequent cause for neonatal seizures is hypoxic-ischemic encephalopathy. Additional

causes include:

Intracranial hemorrhage (subarachnoid in term, germinal matrix in preterm)

Metabolic disturbances (hypoglycemia, hypocalcemia, drug withdrawal, amino acidemias,

organic acidurias, urea cycle defects)

Infection: TORCH infections (TOxoplasmosis, Rubella, Cytomegalovirus, Herpes simplex

virus), Escherichia coli, Streptococcus pneumoniae

Malformations of cortical development

Benign neonatal or infantile familial convulsions

6. What tests should be done for a neonate experiencing seizures?

Initially, send serum electrolytes, including glucose, calcium, and urine toxicology. Request an

ammonia level (free ﬂowing collection), looking for a urea cycle defect. Unless another cause

is found, a lumbar puncture (LP), looking for infections, should be performed. Studies on the

cerebrospinal ﬂuid (CSF) should include cell count, protein, glucose, amino acids, lactate,

pyruvate, Herpes polymerase chain reaction (PCR), and evaluation for xanthochromia (prior

bleed). TORCH studies can also be performed. Serum amino acids and urine organic acids

can be tested for other inborn errors of metabolism.

Cerebral imaging studies include ultrasound, computed tomography (CT) scan, or

magnetic resonance imaging (MRI). MRI is the gold standard. Although expensive and often

requiring sedation, MRI will identify malformations of cortical development. Though easier to

obtain, CT has less resolution than MRI and exposes the newborn to radiation. Ultrasound is

portable and convenient but does not allow the cortical convexities to be well viewed and may

have limited availability. An electroencephalogram (EEG) may be ordered on an inpatient basis.

7. What medications are used to treat neonatal seizures?

There is a dramatic lack of evidence that any drug is useful in the treatment of neonatal

seizures. For a long time, phenytoin, phenobarbital, and lorazepam have been used. Currently

some of the newer medications including Topamax and Keppra are being used for neonatal

treatment.

8. What are common reasons for a child to have a seizure?

Common reasons include:

Fever

Lack of compliance to antiepileptic medication

Infection

3. What things should be sought on physical examination?

Perform a complete neurological examination on any child with a ﬁrst time seizure.

Components of the examination include:

Mental status

Cranial nerves

Motor skills

Coordination

Reﬂexes

Sensation

Gait

Chapter 61 SEIZURES IN INFANCY AND CHILDHOOD426

Trauma

Metabolic abnormalities

Toxins

Tumor

Genetics (channelopathies, chromosomal abnormalities)

9. What is the deﬁnition of a febrile seizure?

According to the National Institutes of Health (NIH), a febrile seizure is an event in infancy

or childhood usually occurring between 3 months and 5 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. A similar deﬁnition,

extending the age range to 1 month, was published by the International League Against

Epilepsy.

10. Are genetics involved with febrile seizures?

Genetic factors are deﬁnitely involved with febrile seizures. Two syndromes that include

febrile seizures are generalized epilepsy with febrile seizures plus (GEFS1) and severe

myoclonic epilepsy. There is a family history of febrile seizures in about one third of

patients. Presence of febrile seizures in an older sibing confers a 20% chance of febrile

seizures in the younger child.

11. What are the types of febrile seizures?

There are two types of febrile seizures: simple and complex. Complex febrile seizures are

those that are focal (4%), those that are prolonged (8%), and those that occur multiple times

during a single day or illness (15%). Approximately one third of all febrile seizures are

complex. If a child has a complex febrile seizure, his or her next febrile seizure is also likely to

be complex.

12. What factors make the recurrence of febrile seizures more likely?

The overall risk of recurrence for febrile seizures is about one third. This is true regardless if it

was a simple or complex febrile seizure. Risk factors for recurrence include:

Early occurrence of ﬁrst seizure

History of febrile seizures in ﬁrst-degree relative

Family history of epilepsy

Abnormal neurological examination

Lower temperature at onset of seizure

Brief period of recognized fever

More frequent illnesses (daycare)

13. What tests should be done following a febrile seizure?

a. Laboratory

Consider completed blood count (CBC), glucose, electrolytes, calcium, magnesium,

urinanalysis (UA), and stool culture, particularly for complex febrile seizures. (See Chapter 60

for further discussion on pediatric fever.) Strongly consider LP if younger than 18 months

with no fever focus.

LP should also be done if there are meningeal signs.

b. Imaging

Nonemergent MRI if focal features

Emergent CT if neurological deﬁcits do not resolve and child does not return to baseline

c. EEG (as outpatient if patient returns to baseline neurologic status)

If complex features or strong family history of epilepsy

14. Under what conditions should a child having febrile seizures be treated and

what treatments should be used?

The two medications that have been shown effective at preventing febrile seizures are

phenobarbital and valproate. There is some question as to whether or not phenobarbital

Chapter 61 SEIZURES IN INFANCY AND CHILDHOOD 427

can impact cognitive ability in children. Depakote is not a good drug for children younger

than 2 years because it can result in fatal hepatotoxicity. Some of the newer drugs are

being tried by practitioners for febrile seizures. Medication should only be started in

consultation with a pediatric neurologist and if having the following features: very frequent

seizures, prolonged seizures, or a family that is far from medical care. Education for the

family is imperative.

Attempts at controlling the fever with agents such as acetaminophen or ibuprofen usually

fail; the seizure is typically the ﬁrst sign of the illness. For patients who have prolonged febrile

seizures, the use of Diastat (rectal diazepam) is a reasonable choice.

15. What is the likelihood that a child suffering febrile seizures will eventually

develop epilepsy?

The risk of a child with simple febrile seizures developing epilepsy is approximately 1%. This

is only slightly above the risk for the general public. The risk of a child with complex febrile

seizures developing epilepsy is about 6%.

16. What are infantile spasms and what are some common causes?

Infantile spasms occur in about 1/3,000 of infants. They typically develop between the

ages of 3 and 8 months. Causes include TORCH infections, malformations of cortical

development, hypoxic-ischemic injury, genetic disorders (tuberous sclerosis, Down

syndrome, neuroﬁbromatosis, Incontentia pigmenti), metabolic disorders (phenylketonuria

[PKU], maple syrup urine disease [MSUD], pyridoxine-dependent seizures), and trauma.

Infantile spasms ﬁrst present as a jerking movement in which the body may ﬂex or extend

suddenly. It is usually a single jerk initially, but after a while, multiple jerks may occur. There is

often a cry during the jerking. The jerk can be unilateral or bilateral. Developmental regression

is a poor prognostic sign.

17. What is the standard treatment for infantile spasms?

The standard treatment for infantile spasm is adrenocorticotropic hormone (ACTH).

ACTH has side effects including hypertension, osteoporosis, and decreased resistance to

infection. Recently this has become exceedingly expensive ($100,000 per course) and

people are now using steroids and other newer drugs such as Levetiracetam or

Topamax. Vigabatrin is a drug that will soon be available in this country and is the

preferred drug in the case of tuberous sclerosis. A side effect of this drug is decreased

peripheral vision.

18. What is the prognosis for infantile spasms?

The prognosis for infantile spasms is quite poor. Mortality has been reported as high as 33%

but is now signiﬁcantly less because of better care. Only 12% of children have normal

intelligence. Data are not sufﬁcient to demonstrate that any drug is effective or that starting

drugs earlier makes any difference.

19. What is the deﬁnition of epilepsy?

Epilepsy is deﬁned as the tendency to have unprovoked recurring seizures. Operationally, it is

deﬁned as an individual who has had two or more unprovoked seizures.

20. What are some common forms of childhood epilepsy?

Childhood absence: Begins from 4 to 8 years old. Involves hundreds of seizures per day.

Typically associated with normal intelligence and normal imaging. Episodes last 5 to

10 seconds with no postictal period. It can be safely reproduced with hyperventilation.

Treatment is with Ethosuximide, or if accompanied by generalized tonic-clonic seizures,

Depakote.

Benign rolandic epilepsy: Begins from 6 to 10 years old. Involves facial and arm twitching,

slurred speech, and drooling. It will occasionally generalize. No treatment is necessary

unless seizures generalize during the daytime.