Epilepsy Treatment in the 21st Century.
The basic approach to medical therapy has not changed, though specific choices of medications have. The choice of antiepileptic medications (AEDs) is based on the seizure type, the epilepsy syndrome, and individual factors such as age, gender, other medical conditions, and which potential side effects are more acceptable to the family. Treatment is initiated with a single AED, which is then gradually increased until seizure control is achieved or toxicity (unacceptable levels of side effects) occurs. If one drug is inadequate, a second drug is introduced. There is some controversy in the medical community over whether the second drug should be added or the first drug should be withdrawn. This is really a risk/benefit issue that needs to be approached on an individual basis. If the second AED is effective, then withdrawal of the first drug should be considered. If two or three AEDS have failed to achieve seizure control, then the child should be considered medically refractory and referred for further evaluation and treatment.
The newer AEDS are being used more and more in children, and it is anticipated that, over the next five to ten years, some may become first-line drugs (i.e., the medication used in the initial attempt to control seizures). They are particularly welcome additions in the treatment of the refractory generalized childhood epilepsies such as the Lennox-Gastaut syndrome. Until recently, only valproate was available as a first-line drug for these syndromes, whereas several of the new drugs are proving effective. However, at present there is insufficient experience with them in children to consider them first-line drugs for children. In particular, more information is needed about possible adverse effects, including behavioral and cognitive, associated with the use of these drugs in children. This is a major focus for future research.
Monitoring the child for adverse effects is a joint venture between the family and clinician. Routine laboratory evaluations of asymptomatic children, though frequently performed, are of little value. Evaluations are necessary when the child develops symptoms. Understanding adverse effects means monitoring children as they use an AED. Each person's physical make-up--height, weight, metabolism rate--determines how he or she responds to medication. For some people the "therapeutic"--or average dose rate--level will actually be "toxic." "Therapeutic" levels are merely useful statistical ranges that help guide treatment and indicate whether there are unusual problems with absorption, metabolism, or compliance for the person taking the medication. Some children are fully controlled with "subtherapeutic" doses. Other children require and tolerate "toxic" doses for control of their seizures. Parents need to be aware that, particularly with the newer drugs, the therapeutic range has not been well defined, and there is no precise correlation between serum levels and biological activity.
For many years, the goal of medical care has been the suppression of seizures without producing unacceptable side effects. This has and will remain unchanged. What has changed is our appreciation of both sides of this effort: seizures and side effects.
We have learned that the majority of children with seizures do well and eventually outgrow their seizures. Isolated seizures, even if prolonged, are only rarely associated with any detectable damage. In the child with occasional seizures, delaying treatment does not affect the long-term prognosis, which is mostly determined by the specific epilepsy syndrome. As for side effects, we have learned that all AEDs are associated with them in some degree. Increasingly, the focus is on the cognitive and behavioral adverse effects of these drugs. While barbiturates are the worst offenders, all AEDs are associated with potential adverse effects on cognition and behavior. This is of particular concern in children with seizure disorders because they have a high incidence of learning disabilities and may be more sensitive to the adverse effects of the drugs.
In children who have been on AEDs since infancy, it is often difficult to know whether the child's problems are due to the underlying disorder or are due, at least in part, to the treatment, since there is no baseline for comparison. While some of the newer AEDs have fewer of these adverse effects, none is free of them. Indeed, it is unlikely that one can suppress abnormal brain activity without interfering with normal brain activity.
The decision to initiate AED therapy, therefore, is increasingly framed in terms of assessing risks and benefits. Many neurologists now recommend no treatment for the child who has rare and brief seizures. On the other hand, we have also learned that there is a small group of children with severe seizure disorders that are unresponsive to medications. In these children, the same risk/benefit analysis leads to the opposite conclusion: Treatment needs to be much more aggressive than in the past. Once a child has "failed" two or three AEDs, the seizures should be considered refractory to treatment. There are now a sufficient number of AEDs that there is a temptation to try them all before going on to other medical or surgical therapeutic modalities. This should be resisted. While the new drugs are welcome additions and are highly effective for some children, none has proven to be a magic bullet that works for all children.
Medically refractory seizures
While the majority of children with seizures will respond to conventional medical therapy with one or two medications, there is a significant minority that are refractory to these drugs. When this happens, the first step is to repeat and expand the diagnostic evaluation.
Proper diagnosis is key to further therapy in difficult cases. Sometimes children do not respond because they have been misdiagnosed. One of the most complicated things to do is to make a diagnosis of neurological problems for a child. Misdiagnosis can occur when the seizure type or epilepsy syndrome is not recognized, leading to an inappropriate choice of medications. It can also occur when a variety of nonepileptic events, which would not be expected to respond to these medications, is misdiagnosed as seizures. Sometimes it is a case of not one diagnosis, but a continually evolving diagnostic situation. The original diagnosis may not be wrong, just incomplete. It can also occur when a variety of nonepileptic events--which cannot be expected to respond to these medications--are misdiagnosed as seizures.
Increasingly, early surgical intervention is considered in children with refractory seizures who may benefit from this approach. Other medical options for young children, particularly those with myoclonic seizures, include the use of high-dose steroids, especially adrenocorticotrophic hormone (ACTH). For some children with medically refractory seizures, the ketogenic diet may also be an option. This is a highly restrictive diet which requires careful medical supervision and is not without side effects. However, it is effective in many children who have not responded to medications. These children may also benefit from participating in trials of newer investigational (experimental) medications, which are now being tried in children at a much earlier stage than previously.
For some parents of children with prolonged seizures or flurries of seizures that may have previously required visits to the emergency room, rectal diazepam (Diastat[R]) is now an option for home therapy. Many school districts will also administer it in school with a physician's order.
Focus of ongoing research
Historically, epilepsy has been the neurological disorder with the shortest time frame from developments in the basic science laboratory to the introduction of new therapies. Current drugs, by and large, suppress seizures quite well, but do not affect the underlying disorder. Future research will focus on several issues, all of which have implications for treatment. Basic science research is now concentrating on more than just the mechanism by which a seizure develops. It is also centering on epileptogenesis: how the underlying seizure focus evolves following an injury or an error in brain development. Identifying these mechanisms may allow the introduction of drugs that prevent epilepsy or at least modify its progression.
Molecular geneticists are collaborating with clinicians in trying to identify the genetic basis for some epilepsies. These are complex disorders that will most likely not be the result of single gene mutations. Finding the gene(s) will allow us to determine the molecular basis for some of these disorders, which will again lead to better treatment and, in the more distant future, potential cures.
In the clinical arena, research is focusing on three areas: early identification, improved diagnostic tools, and nonseizure outcomes. Early identification implies the ability to recognize, early on in the disorder, which children will require conventional therapy and which children will go on to develop intractable seizures. If we can identify this second subgroup early, then aggressive intervention at the beginning of the disorder may improve long-term outcomes for these children.
Improvement in localization techniques is a necessary part of this approach. We need to be able to identify the epileptic area within the brain in order to provide aggressive interventions. (See "Advances in Pediatric Epilepsy" by Mary Zupanc, MD, below.)
A new focus is on non-seizure outcomes. We now recognize that many children may do well in terms of their seizures, but not in terms of psychological impact, cognition (learning) and school performance, and behavior. Current research is focusing on identifying the relevant factors, which we hope will lead to early intervention and improved outcomes.
What parents can do
To be effective advocates, parents need to be informed. The Epilepsy Foundation and its local affiliates provide information for parents, children, and caregivers, as well as help with advocacy issues. It can keep parents abreast of new developments in and approaches to treatment.
Parents need to be actively involved in the treatment of their child's seizure disorder. When seeing the clinician, they need to discuss any changes they have noted in their child after medications or dosages are changed. Treatment should be a team effort. Most children will not have seizures in the office, and subtle changes in personality and behavior are best noted by the parent. Seizure diaries are helpful in recounting behavior and determining whether the new medication is working.
Parents also need to advocate for their children in school. After all, the long-range goal is to produce an adult whose potential is not hindered by his or her seizure disorder. This requires a good education. Many children with seizure disorders do not function as well as they should in school due to a combination of biological (the underlying brain disorder), iatrogenic (medications) and psychosocial (stigma; not being pushed by parent or school because of the epilepsy factors). If a child is not doing well academically, this should be investigated. In many cases, intervention is possible if the cause is identified early enough.
Epilepsy is one of the most frightening neurological disorders, but it is also one of the more treatable ones. The advances in both basic and clinical research give us hope that an ever higher proportion of these children will have effective treatment available that will allow them to lead a full life.
Shlomo Shinnar, MD, is Professor of Neurology and Pediatrics, Albert Einstein College of Medicine, and Director of the Comprehensive Epilepsy Management Center, Montefiore Medical Center, Bronx, NE. The recipient of the American Epilepsy Society Research Recognition Award, he is well known for his research on childhood epilepsy. Dr. Shinnar is active in a variety of professional organizations, including the Epilepsy Foundation and American Epilepsy Society.
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|Publication:||The Exceptional Parent|
|Date:||Oct 1, 1999|
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