Epilepsy in Childhood

Dr. Jesus Gomez-Placencia, MD, PhD

Epilepsy is defined by the World Health Organization as a "chronic affection of diverse etiology, characterized by repeating crisis, due to an excessive overload of brain neurons, eventually associated with many clinical and paraclinical manifestations" (1). Expressing it in other words, certain pathological changes in brain cells cause an abnormal activity that manifestes itself in several ways, such as repeated spasmodic muscle contractions of different parts of the body (convulsions), psychological and sensory anomalies, etc.

In all countries, epilepsy represents an important public health problem, not only for its high incidence,

estimated to be of 18 cases per 1,000 inhabitants, but also for the repercussion of the disease, including the recurrence of its crises, the incapacities and sequellae provoked by some of its consequences, and the suffering due to social restricitions, which most of the times are not justified (2).

The incidence in the pediatric population is relatively high, since we must remember that 75% of all epileptic patients have the onset of disease before the age of 18 (3). That's why is so important to the diagnosis make as early as possible and to establish a proper treatment, with the application of the fundamental principles of child anti-epileptic therapy. It is also important to establish a proper management of the relevant psycho-socially aspects and to offer a complete reintegration to the family, and to the educational and social environments.

One of the medical fields where the differences between adults and children are most important is precisely Neurology, especially regarding epilepsy. The main reason for this is that the child's central nervous system (CNS) is in a dynamic state of constant change. Its formation occurs in the first weeks after conception, but its maturation continues well until the adult age. As a result of these active changes, the child can develop epileptic crises in ways that are not present in the adult (2-4).

Furthermore, certain epileptic syndromes appear only in a specific range of ages, and the crisis' clinical manifestations modify with age. For example, there is a incapacity of the recently born child to develop certain severe crises, called tonic-clonic convulsions. The febrile episode (convulsions that appear after a high fever) appear only between six months and five years of age, etc. The sensibility to different drugs also modifies with time, not only in function of changes in the type of crisis, but also due to changes in drug metabolism, which are directly dependent on age (5-7).

The Rational Treatment of Epilepsy

The institution of a more rational treatment for epilepsy in childhood, entailing better control and outcomes, depende on several factors:

  1. The adequate identification of different epileptic syndromes;
  2. The therapeutic specificity of these syndromes (for example, febrile crises are controlled mainly by phenobarbital or valproate);
  3. The knowledge about the changes in drug metabolism in relation to age;
  4. The possibility of carrying out tests in order to determine the plasma levels of anti-epileptic drugs;
  5. The application of other criteria, which we will review later.

Among the consequences of a rational approach to treatment we have a lower incidence of possible secondary effects, a better cost-benefit ratio (both at particular and institutional levels) and a more adequate family, educational, cultural and social integration of the epileptic child.

To begin a rational management of the patient, once diagnosis for epilepsy has been confirmed, one must always take in account that observed disease could be the initial manifestation of specific pathologies which are decreasing the threshold for brain discharges. Thus, the neurologist should discard first the existence of a potentially treatable lesion which could be approached by other means or which is putting the patient's life in danger.

The Diagnosis

The physician must proceed, first, to taking a detailed patient history, followed by careful physical and

neurological exploration. EEG (eletroencephalogram) and neuroimage studies are required in most of the cases. In some cases, it is also necessary to determinate whether there is a progressive neurological pathology which will require specific therapy (for example, an intracranial tumor, a degenerative nervous disease, brain cisticercosis, etc).

After this, the physician should categorize the patient's disease according to a crisis model, as specified by the International Classification of Epileptic Crises (Table 1) (8), which distinguishes basically two types of crisis:

Partial or focal crisis (because they are restricted to some parts of the brain, beginning usually as a "focus" of abnormal activity in a specific point, but not spreading through all other parts of the brain);

General crisis, because they spread through most of the brain.

The classification describes the different models, with their relevant eletroencephalographic manifestations, either ictal and interictal (that is, during or after the crisis). This classification is necessary because one should clearly recognize the different clinical and eletroencephalographic manifestations for the different types of epileptic crises, not only from the clinic-therapeutical point of view, but also from the prognostic and physiopatologic points of view (9) .

The Treatment

Once the diagnosis has been established , treatment must be initiated. In order to choose the best route of treatment, four basic questions, related to its continuation, must be answered:


When to treat ?

This first question is related to when the physician should start an anti-epileptic treatment, which, once established, will be mantained for a long period of time. This question is particulary critical in the cases of children who already have had their first convulsion, remembering that ca. 5% of all healthy children will present a crisis before 10 years of age, and that there are some types of epileptic crises which are essentially non-recurring (10) and which must be diagnosed differentially.

The therapeutical decision is important, since after the first crisis there is a 25 to 75% risk of recurrence that gets higher to 65 to 95% after two or more crises (11, 12). Although these numbers represent a statistical probability, there are many risk factors that allow the neurologist to determine with higher precision the probability of recurrence (11).

More precisely, children who already had a crisis should get a closer evaluation by the pediatric neurologist. This professional has a specific scientific and technical background for this, so that he/she is able to order additional workup studies in a rational way (13), and to interpret them adequately, thus proposing the right course of patient management, before referring the patient back to the physician who will be responsible for follow-up and control. It is recommended, also, that this patient returns to the pediatric neurologist for a periodical re-evaluation.

Once determined the necessity of a pharmacological treatment, we pass to the second question.


CNS history lesion

EEG with epileptogenic discharges

Neurological exams with lateralization data

Positive family history in first degree relatives

Which Treatments to Use ?

Since this is a practical guide to patients and non-specialist physicians, we'll mention only those anti-epileptic drugs of choice for the three main types of epileptic crises. Additional information about other pharmacological and non-pharmacological treatments for specific epileptic syndromes should be sought by the reader in textbooks and reviews on epilepsy or pediatric neurology (14).

For the general tonico-clonic crises (convulsions which take all members, with rigid extension followed by movements of agitation in the limbs), the following drugs are considered to have the same clinical effectivity (2):

For partial crises of any kind (simple or complex, or with secondary generalization) diphenilhydantoin, carbamezepin and phenobarbital have demonstrated similar usefulness (2). For practical clinical purposes, primidone is considered similar to phenobarbital in relation to its range of action and secondary effects that it may present.

On the other hand, for the typical absence crisis, the drugs of choice are nowadays:

The choice of any of these drugs depends on the circumstances of a given patient, especially the availability of drugs in the region, the patient's age, the cost of treatment (which should be considered in the context of the health care institution) and secondary effects, which can be systemic (gastrointestinal, hepatic or hematologic) or central. A careful use should be made of valproate, due to its potential hepatotoxicity, which can be fatal, specially if associated to other drugs before 2 years of age. Careful consideration should also be given to the effects of some of these drugs over the child's cognitive and behaviour functions. The behaviour changes are more frequent with phenobarbital and clonacepam, while cognitive functions are more affected by diphenilhydantoin and much less with valproate. Carbamazepin has minimal effects in releation to this (15). The gradual increment of the dose until reaching therapeutical levels is a good method to decrease secondary central effects. It is always important to inform parents that they should not suspend medication by their own initiative in case secondary effects appear.

How to Treat Epilepsy ?

Once the most convenient drug is selected for the patient, according to his or her type of crisis, age, etc., it must be determined what is the better way to deliver it. For this, one should consider two important aspects for the pediatric patient in general:

1) The dose,

2) The time.

Both of them vary with age (5-7); for example let's consider diphenilhydantoin. This drug must be ministered orally in doses recommended by the neurologist, that vary with age. In lactants, it may be necessary to minister the drug in a fractionated way, every 4 or 6 hours, and increase the interval between doses for higher ages. In adolescents and adults it is possible to minister the drug in a unique daily dose (7).

The optimized therapy which takes in account these factors should be able to mantain drug levels in the body in a stable manner, with minimal fluctuation between consecutive doses (16).

Most of the patientes can be controlled effectively with one drug only, and the authors' experience has shown that monotherapy is the more rational and useful way of controlling the epileptic patient.

In our experience, the three most frequent causes of inadequate control are:

1) A failure in taking the medication regularly,

2) A prescribed periodicity of dosage which doesn't take into account the drug's mean life;

3) Prescription of drug which are not indicated for the type of crisis (for example, diphenilhydantoine for febrile crisis, drugs that allow the onset of other crises, or the incorrect identification the epileptic syndrome).

If the last possibility is excluded, one must take into consideration that there is a higher individual variability of drug metabolism in children. Therefore, the quantitative determination of plasma drug levels is recommended, so that deviations from the average are detected and optimized.

However, knowledge about circulating levels of the drug is useful for some drugs, such as diphenilhydantoin, carbamazepin and phenobarbital (but less so for valproic acid), but not for other drugs, such as the benzodiazepines (16b). In the first group, there is a good correlation between therapeutic levels in the blood and crisis control. Determination of plasma levels of the substance has greater utility in the case of diphenilhydantoin, since small modifications in dosage may lead to significant fluctuations in its blood levels (5); while for valproic acid this knowledge has no great importance in terms of its clinical effects. (16c). It must not be forgotten that the concept of therapeutic range is relative, representing a statistical compromise and that even when there is large variations, especially with children, one should know how to exploit well the behavior of the drug to be used. (17).

When follow up shows that the drug has been used incorrectly, it may be substituted by another drug of choice, but we recommend to avoid adding another drug to the first one, because there are many important interactions which may lead to alterations in the plasma concentrations, by decreasing them to levels which are unable to provide therapeutic effect or by increasing them to toxic effects. In other cases, a combination of drugs may be dangerous, because there is a sum of their effects, leading to cognitive impairment. For example the combination of clonazepan and valproic acid may cause absence effects.

Usually, the experience in the management of epileptic patients of any age agrees with the affirmation that "...the multiplication of the number of anti-epileptic drugs ministered simultaneously more probably will multiply the number of secondary effects than increase crisis control" (17). In our Epilepsy Clinic many of the patients referred to us with a diagnosis of "difficult crisis" had been receiving treatment with multiple drugs, in some occasions even four to five combined drugs. We were able to restore control by eliminating all drugs except the drug of first choice, according to the principles we have discussed.

What happens if the patient does not respond to the second drug of choice ? Then it is recommended that na in-depth evaluation should be carried out by the pediatric neurologist, who can resource to more specialized diagnostic studies and patient management procedures, especially for those patients who could not be controlled from the very beginning, although they were receiving the indicated dosage. Another possibility is that the epileptic syndrome was misidentified clinically or electroencephalographycally due to inadequate or incomplete information.

Recently there has been an increase in the availability of new anti-epileptic drugs, which have been developed as a result of a better knowledge of some of the physiopathological mechanisms in epilepsy. In our experience with some of these drugs, such as lamotrigine, vigabatrine and gabapentine, we have found that their most useful indication is as second drugs to the first line anti-epileptic agents such as carbamazepine, oxcarbamazepine or diphenilhydantoíne (rational politherapy).

On the other hand, we have found that vigabatrine may be considered as a drug of choice for spasms of any etiology in children, alone or combined with valproic acid. Lamotrigine has demonstrated special

utility in the treatment of Lennox-Gastaut syndrome.

I consider that at least for the moment the utilization of these drugs should be kept in the neurologist's hands..

How Long to Treat ?

In relation to the duration of treatment, we feel that the information which is usually given to the child's parents, i.e., that epilepsy is incurable and that therapy will take the entire life of patient is not only obsolete, but also dangerous, because it will have important consequences for the patient and his family.

There is all evidence in the medical literature, with basis on prospective studies with a very long duration, that 75 to 88% of patients who have been free of epileptic crises for a period of 3 to 4 years will not show recurrence if treatment is suspended (18-20b). In we list the main factors associated with a favorable prognosis (20b,21).

These data have statistical validity for a general population only. Evidently, final prognosis for any given patient will depend on the primary pathology which causes the crisis and in many cases, on the specific type of epileptic syndrome. When the neurologist is considering the suspension the pharmacological treatment, we advise that a rigorous evaluation should be carried out, including the review of EEG tracings by the pediatric neurologist.


Normal psychomotor development

Normal intelligence

Absence of neurological signs

Started after 2 years of age

Low frequence of crisis

Only one type of crisis

Good response to treatment

Fast EEG improvement wiht treatment.


Jesus Gomez-Placencia, MD, PhD Full Professor, Dept. of Neurosciences, University of Guadalajara, Medical School University of Guadalajara Training in Neurology and EEG at the Hospital Civil de Guadalajara and the GREM Postgraduate Studies: Cell Biology -Neurobiology- Past President Mexican Chapter of the International League Against Epilepsy President, Mexican Pediatric Neurology Society. Email: jgomezp@udgserv.cencar.udg.mx

Translated to English by: Marcelo Sabbatini and Renato M.E. Sabbatini

Center for Biomedical Informatics
State University of Campinas, Brazil

Copyright 1997 State University of Campinas