Approach to a child with a first afebrile seizure

Afebrile seizures have many causes. Physicians attempting to determine the cause of an afebrile seizure should obtain more information with the help of a detailed clinical history, electroencephalography, and neuroimaging. Antiepileptic medi­cations are rarely indicated after a first afebrile seizure. In all cases of afebrile seizure, physicians should provide support to the family.


The clinical history is key when determining the likelihood of recurrence after a child experiences a first afebrile seizure.


Epilepsy is a common neurological disorder in childhood. Although most children who have an epileptic seizure do well, the diagnosis of such a seizure in a child can cause considerable anxiety for the parents. A physician managing a child following a first afebrile seizure should try to answer five questions:

1. Was the episode an epileptic sei­zure?

2. What is the cause of the seizure?

3. What investigations should I do?

4. Does the child require treatment? 

5. What else should I think about?

1. Was the episode an epileptic seizure?
When a child presents following a transient neurological event, making the correct diagnosis is paramount. A misdiagnosis of epilepsy is made in a significant proportion of children who have never had an epileptic sei­zure.[1,2

Up to 30% of children re­ferred to a first seizure clinic have not had an epileptic seizure.[3,4] Some of the more common nonepileptic paroxysmal episodes include:

• Day dreaming.

• Stereotypies and tics.

• Panic/anxiety attacks.

• Psychogenic nonepileptic seizures (formerly called pseudoseizures).

• Sleep disorders.

• Migraine (complex).

• Transient ischemic attack/stroke.

• Paroxysmal movement disorder.

Causes of syncope and reflex anox­ic seizure include:

• Vasovagal syncope.

• Breath-holding spells.

• Orthostatic hypotension.

• Cardiac abnormalities (prolonged QT, other arrhythmia).

• Gastroesophageal reflux (Sandifer syndrome).

• Hyperventilation syncope.

Taking a good history is key to distinguishing an epileptic seizure from a nonepileptic event. It is important to speak to both the child and the person who witnessed the event. This should be done by telephone if necessary. The key factors to elicit in the history include: 

• The setting in which the event oc­curred. Breath-holding spells are often triggered by pain, anger, or frustration. 

• The observations of the witness at the start of the event. Pallor is typically observed during a vasovagal or syncopal event.

• How the patient felt just before and at the start of the event. Patients who experience a syncopal event commonly describe lightheadedness, nausea, and a fading out of vision, hearing, or both prior to loss of consciousness.

Syncope can result in generalized clonic jerking, loss of consciousness, and incontinence, and may be misdiagnosed as an epileptic seizure. These clinical features occur as a result of a sudden decrease in oxygen to the brain, either because of a reduction in cerebral blood flow or a reduction of the oxygen content in the blood,[3,5] and are not epileptic in nature. 

An electrocardiogram (ECG) should be obtained in children with possible syncope or anoxic seizure to exclude prolonged QT interval and other cardiac causes. A helpful website for families of children with syncope or anoxic events is www.stars.org.uk.

Although electroencephalography (EEG) is useful in characterizing the type of epilepsy and in the selection of an antiepileptic medication, it can be very misleading in determining wheth­er the child has had an epileptic seizure. 

Normal EEG results are found in up to 50% of children who have had an epileptic seizure.[6] In addition, 3% to 4% of children who have not had an epileptic seizure have genetic epileptiform abnormalities on their EEG findings, such as generalized spike-wave discharges or rolandic spikes.[7] Thus, normal EEG results do not ex­clude a diagnosis of epileptic seizure, and the finding of epileptiform discharges on an EEG is not diagnostic of an epileptic seizure. 

As mentioned above, the clinical history is the key to the diagnosis of paroxysmal events and should guide the selection of further investigations.

2. What is the cause of the seizure?
Epileptic seizures are symptoms associated with a variety of clinical factors (see Table 1). Determining the underlying cause of the epileptic seizure has implications for both treatment and prognosis. 

Approximately 50% or more of children with epilepsy do not have a brain lesion, and genetic factors predispose them to recurrent seizures.[8] The term idiopathic has been used to describe this genetic predisposition to epileptic seizures, while the term symptomatic is used when an underlying brain abnormality is involved (see Table 2).[9

Three common idiopathic epilepsies are absence epilepsy, benign rolandic epilepsy, and juvenile myoclonic epilepsy. Children who have idiopathic epileptic seizures have normal neurological development and normal findings upon neurological examination. There is no history of a serious neurological insult such as meningitis or head injury, and there is often, but not always, a family history of epilepsy. 

Children who have idiopathic epileptic seizures nearly always have characteristic epileptiform discharges on an EEG. Thus, EEG can be used to confirm the clinical suspicion of an idiopathic epileptic seizure.

Approximately 50% of children with epilepsy will have an underlying brain abnormality that is the cause of the seizures.[8] The epilepsy is called symptomatic when the underlying cause can be shown and is called probably symptomatic (or cryptogenic) when an underlying brain lesion is suspected but cannot be demonstrated. 

Abnormalities of brain development are the commonest cause of symptomatic epilepsy. When seizures occur as a result of previous trauma, infection, hypoxia, or stroke, there is usually a significant past medical history. 

Vascular brain abnormalities, brain tumors, and inborn errors of meta­bolism are rare causes that re­quire specific treatment. The possibility of a symptomatic epileptic seizure is suggested by a history of delayed neurological development, abnormal results from a neurological examination, a history of previous neurological insult, or the presence of dysmorphic features or other congenital abnormalities.

3. What investigations should I do?
A child presenting immediately after a first epileptic seizure should have a blood glucose test. Further laboratory investigations should be guided by the clinical features at that time—for example, a history of vomiting, fever, or illness. 

Toxicology testing should be considered if accidental ingestion of a toxic substance is possible. If the clinical history suggests a possible syncopal or reflex anoxic seizure, an ECG with QT corrected interval calculation should be performed. These investigations are relatively easy to obtain and may help to exclude a number of nonneurological causes of seizures.

Electroencephalography
Electroencephalography is the most useful investigation following an afeb­rile epileptic seizure. Although EEG results can be misleading in the diagnosis of an unusual event, they are particularly helpful in children who have had a definite epileptic seizure. 

An electroencephalogram can be used to assess the risk of seizure recurrence, determine whether the child has an idiopathic or a symptomatic epilepsy, and guide the selection of an appropriate antiepileptic drug.[10-12

For example, a child with a first generalized tonic-clonic seizure who has generalized polyspike and wave on EEG has a high risk of seizure recurrence, is highly like to have an idiopathic epil­epsy, and is more likely to respond to certain antiepileptic medications (e.g., valproic acid, lamotrigine, topiramate or levetiracetam). 

It is important to perform a sleep-deprived EEG, since the likelihood of detecting epileptiform discharges increases during sleep.

Neuroimaging
Patients with a clinical history and EEG findings consistent with an idiopathic epilepsy, such as childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy, and benign childhood epilepsy with centrotemporal spikes (benign rolandic epilepsy), do not require brain imaging. 

Brain imaging should, however, be performed in children who have had two or more afebrile epileptic seizures and who do not have the clinical or EEG features of an idiopathic epilepsy.[11

Although MRI is superior to CT in demonstrating subtle brain developmental abnormalities,[11] the choice of imaging modality will be influenced by the availability of MRI and the need to administer a general anesthetic to young children during the MRI.

Although neuroimaging abnormalities occur in up to one-third of children with a first afebrile seizure, only 2% demonstrate clinically significant abnormalities that influence management.[11] Seizures are an uncommon presenting symptom of a brain tumor in children. 

Thus, brain imaging (CT or MRI) in the emergency department following the first afebrile seizure is usually not warranted. Emergency neuro­imaging should therefore be considered only in a child who:

• Presents with afebrile status epilepticus. 

• Has focal neurological signs that persist for several hours.

• Has had recent head trauma, persistent headache, or history of cancer or anticoagulation.[11,13

• Is not returning to baseline within several hours of the seizure.

4. Does the child require treatment?
Antiepileptic drug treatment is not usually started after the first unprovoked focal or generalized tonic-clonic seizure because most children only have one or two seizures. 

Fifty percent of children who have an epi­leptic seizure will never have another seizure and 20% of children who have two epileptic seizures will never have another seizure.[12

In addition, seizures lasting less than 30 minutes do not result in brain damage and failure to prevent the first several seizures does not alter the overall prognosis.[14-17

Although only 50% of children who have an epileptic seizure will have a recurrence, certain factors are known to increase the risk of a second seizure:

• Focal (partial) seizure.

• Abnormal neurological examination.

• Developmental delay.

• Seizure begins while asleep.

• Family history of epilepsy.

• Epileptiform discharges shown on EEG.

The physician can individualize the seizure recurrence risk based on a careful history and EEG results. The decision to initiate antiepileptic therapy should be made by the parents, the physician, and child if he or she is old enough. Factors that might influence the decision include: 

• The risk of seizure recurrence. 

• The degree of patient or parental anxiety about a further seizure.

• Whether the family lives in an area remote from medical help. 

Early treatment might also be considered in the child who has status epi­lep­ticus as the initial seizure. Although the recurrence risk for a second sei­zure (50%) is not increased following status epilepticus, if a second seizure oc­curs, it is more likely to be prolong­ed. For that reason, it may help to provide the family of such a child with res­cue anticonvulsant medication to abort a seizure. 

The parents can be shown how to use rectal diazepam (0.5 mg/kg; max­imum dose 10 mg) or buccal midazolam (0.3 mg/kg; maximum dose 10 mg) for sei­zures lasting 5 minutes or longer.

5. What else should I think about?
A child who has a first afebrile seizure should be evaluated by a physician with experience in the management of children with epilepsy. 

Children with infantile spasms, multiple sei­zure types, and those who have not achieved seizure control after two antiepileptic medications should be referred to a pediatric neurologist. Re­ferral to a pediatric neurologist should also be considered if a focal lesion is demonstrated on neuroimaging, there is uncertainty as to seizure type or epilepsy syndrome, and when the sei­zure is associated with developmental delay or regression. 

It is important to consider the needs of the family as well. Seizures are frightening and many parents who witness a first seizure fear initially that their child is dying. A diagnosis of epileptic seizure in a child can consume a parent with worry about issues such as the possible cause, the possibility of brain damage, and the prognosis for intellectual outcome. 

The possibility of side effects of anti­epileptic drugs is also a major concern for many parents. These concerns may explain why approximately one-third of mothers of children with newly diagnosed epilepsy exhibit symptoms of posttraumatic stress disorder or major depressive disorder.[18

Education of the child and parents about seizures, epilepsy, and medication plays an important part in reducing the emotional stress on the family. Providing the child and family with written material on epilepsy and anti­epileptic medications can be very helpful. 

It is important to review ap­propriate seizure precautions with the family, including proper positioning of a child during a seizure and issues regarding water safety and driving. 

The British Columbia Epilepsy Society website has detailed information sheets in several languages (www.bcepilepsy.com). Another reliable re­source for families is www.epilepsy.com. Children or parents who continue to have a difficult time coping may benefit from referral for psychological counseling.

Summary
Afebrile seizures are a common childhood problem presenting to primary care physicians. A detailed clinical history of the episode is the most important step in making a diagnosis. The clinical history and EEG findings will help physicians determine the underlying cause of the seizure and calculate the probability of seizure recurrence. 

Brain imaging should be carried out in patients who do not have the characteristic features of an idiopathic seizure. Antiepileptic drug treatment is not usually started after a first unprovoked seizure unless the clinical or EEG features suggest a high risk of recurrence.

Competing interests
None declared.

This article has been peer reviewed.


References

1. Desai P, Talwar D. Nonepileptic events in normal and neurologically handicapped children: A video-EEG study. Pediatr Neurol 1992;8:127-129.
2. Uldall P, Alving J, Hansen LK, et al. The misdiagnosis of epilepsy in children admitted to a tertiary epilepsy centre with paroxysmal events. Arch Dis Child 2006;91:219-221.
3. Stephenson JBP. Fits and faints. Clinics in developmental medicine No. 109. London: Mac Keith Press; 1990.
4. Hamiwka LD, Singh N, Niosi J, et al. Diagnostic inaccuracy in children referred with “first seizure”: Role for a first sei­zure clinic. Epilepsia 2007;48:1062-1066. 
5. Stephenson JBP. Anoxic seizures: Self-terminating syncopes. Epileptic Disord 2001;3:3-6.
6. Smith SJ. EEG in the diagnosis, classification, and management of patients with epilepsy. J Neurol Neurosurg Psychiatry 2005;76:ii2-ii7.
7. Cavazzuti GB, Cappella L, Nalin A. Longitudinal study of epileptiform EEG pattern in normal children. Epilepsia 1980;21:43-55.
8. Hauser WA, Hesdorffer DC. Epilepsy: Frequency, causes and consequences. New York: Demos; 1990. p. 28-37.
9. Engel J Jr; International League Against Epilepsy. A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: Report of the ILAE Task Force on Classification and Terminology. Epilepsia 2001;42:796-803.
10. King MA, Newton MR, Jackson GD, et al. Epileptology of the first-seizure presentation: A clinical, electroencephalographic, and magnetic resonance imaging study of 300 consecutive patients. Lancet 1998;352(9133):1007-1011.
11. Hirtz D, Ashwal S, Berg A, et al. Practice parameter: Evaluating a first nonfebrile seizure in children: Report of the Quality Standards Subcommittee of the American Academy of Neurology, the Child Neurology Society and the American Epilepsy Society. Neurology 2000;55:616-623.
12. Shinnar S, Berg AT, Moshe SL, et al. The risk of seizure recurrence after a first unprovoked afebrile seizure in childhood: An extended follow-up. Pediatrics 1996;98(2 Pt 1):216-225.
13. Matyal J, Krauss JM, Novak G, et al. The role of brain computer tomography in evaluating children with new onset seizures in the emergency department. Epilepsia 2000;41:950-954.
14. Shinnar S, Hauser WA. Do occasional brief seizures cause detectable clinical consequences? Prog Brain Res 2002;135:221-235. 
15. Marson A, Jacoby A, Johnson A, et al. Immediate versus deferred antiepileptic drug treatment for early epilepsy and single seizures: A randomised controlled trial. Lancet 2005;365(9476):2007-2013.
16. Musicco M, Beghi E, Solari A, et al. Treatment of first tonic-clonic seizure does not improve the prognosis of epilepsy. First Seizure Trial Group. Neurology 1997;49:991-998.
17. Camfield PR, Camfield CS, Smith S, et al. Long-term outcome is unchanged by antiepileptic drug treatment after a first seizure: A 15-year follow-up from a randomized trial in childhood. Epilepsia 2002;43:662-663.
18. Iseri PK, Ozten E, Aker AT. Posttraumatic stress disorder and major depressive disorder is common in parents of children with epilepsy. Epilepsy Behav 2006;8:250-255.

 


Dr Michoulas is a pediatric neurology resident at BC Children’s Hospital. Dr Farrell is a neurologist at BC Children’s Hospital (BCCH) and a professor in the Department of Pediatrics at UBC. Dr Connolly is a pediatric neurologist at BCCH and a clinical professor in the Department of Pediatrics at UBC.

Aspasia Michoulas, BSc Pharm, MD,, Kevin Farrell, MBChB,, Mary Connolly, MBBCh, FRCPC,. Approach to a child with a first afebrile seizure. BCMJ, Vol. 53, No. 53, July, August, 2011, Page(s) 274-277 - Clinical Articles.



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