More than 16 percent of patients with epilepsy conceal seizures from their doctors, according to a recent study. Previous research has reported that many people with epilepsy hide it to avoid social stigma and loss of employment or driving privileges.

Researchers, from the University of East Anglia in Norwich, England, and at King’s Fund in London, distributed two identical questionnaires to 111 adult patients who’d had epilepsy for an average of 21.5 years. The first questionnaire was completed with the general practitioner at an office visit, and the second was completed anonymously by the same patients about two weeks later. The researchers compared the two questionnaires for each patient.

Forty-two patients (38 percent) told their doctors that they’d had a seizure within the past year. Sixty patients (54 percent) admitted this on the anonymous questionnaire. The researchers suggest that an important reason for not telling the doctor is to keep driving privileges. In England, patients must be seizure-free for 12 months to drive. Six of the 42 patients who told their doctors about seizures still had a driver’s license, compared to 24 of the 60 who admitted anonymously to having seizures.

Another reason for concealing seizures may be to maintain employment. About 47 percent of the patients who told their doctors about seizures were unemployed, compared to 17 percent of those who concealed their seizures.

Patients who’d had seizures in the past year, whether or not they’d told their doctors, were also significantly more likely to be anxious or depressed or to feel stigmatized, than those whose epilepsy was controlled.

Writing in the January 8, 2000, issue of the British Medical Journal, the researchers conclude that while concealing seizures may prevent these patients from getting the best care, many consider that price worthwhile if it allows them to keep driving and working.

The researchers also point out that the doctor’s role in determining whether patients with epilepsy can drive or participate in other activities hampers their ability to provide appropriate care for those patients. They suggest that driving regulations for people with epilepsy be changed. They noted that in Wisconsin, which has a low accident rate, epileptics only need to be seizure-free for three months to drive.

The authors also call on general practitioners to explain to their patients that they must report their seizures if they want to receive optimal care.

A conservative estimate is that more than 100,000 people with epilepsy in the United States alone have uncontrolled seizures and could benefit from surgery. Most of them have seizures that arise from a problem in a temporal lobe of the brain, and the most common operation to treat refractory epilepsy is anterior temporal lobectomy. This is a procedure with a proven record of efficacy, eliminating or greatly reducing the prevalence of seizures in trial after trial. A group of researchers at the University of Pennsylvania and Dartmouth University decided to delve deeper into the impact of this procedure on the lives of patients in the first five years after lobectomy.

The test subjects were 89 volunteers, ranging from 10 years old to 60, all suffering persistent seizures at least once a month for at least one straight year. All had elected to have surgery after at least three different antiepileptic drugs (AEDs) and one attempt at combination therapy failed to improve their condition. Neurologists had confirmed in each case that their seizures probably arose from a single temporal lobe and could therefore be addressed by its excision; all those patients whose seizures originated in more than one site, or in a site other than the temporal lobe, were excluded from surgery because of the obvious undesirability of removing large or valuable pieces of brain tissue. Surgery does not immediately cancel the need for medication; patients were initially advised to continue taking their AEDs at moderate doses for two years after study, and this was later extended to five years.

The results of surgery

The most basic yardstick for measuring the value of any surgery aimed at reducing seizures is obviously the impact on seizure frequency. This was documented at two weeks, two months, six months, and again at one year after surgery. Follow-up continued every year in those patients who were seizure-free to see how long they stayed that way. Patients were grouped into four categories according to the degree of improvement. Class One patients were seizure-free after surgery, or currently seizure-free for at least one year (exceptions were made for isolated seizures associated with withdrawal of medication). Class Two patients were those who still had occasional seizures, but no more than three in a year – a significant improvement in a group that had previously averaged at least eight seizures per month. Class Three patients had more than three seizures in a year, but still registered a post-surgery reduction of over 80% in seizure frequency. Finally, Class Four patients included all patients whose seizures had become less frequent, but by less than 80%, and those who had registered very little improvement or none at all.

By any standards, the surgery was very effective. After five years, 62 patients (70%) were in Class One, a further eight (9%) were in Class Two, and 10 more (11%) were in Class Three. Thus, 90% of patients had achieved significant relief from their seizures, and most of them were effectively cured. Only five patients (6%) had fallen into Class Four, while four (4%) had died of various causes, none of them related to surgery. More than half of all patients never had another seizure following surgery. (This does not include those seizures that sometimes follow immediately after the operation, which are caused by the trauma to the brain inherent in surgery, and do not reflect any permanent epileptic condition.)

Lobectomy does not impair intelligence

One common misconception about lobectomies (arising, no doubt, from the connotations of the similar word lobotomy) is that it can reduce intelligence. IQ tests administered to patients before and one year after surgery showed no change in verbal scores and a noticeable improvement in the performance score, especially among those who had left (as opposed to right) temporal lobectomies. Both left and right-side patients (especially left) raised their average overall IQs. Thirty-minute visual memory and facial memory were also improved. Most importantly, the patients showed greatly reduced scores on standard tests of depression and anxiety; they were happier and more relaxed.

These changes could not be expressed more clearly than in the improvements that those patients who became seizure-free achieved in their own lives over the five years following surgery. Before the operation, only 34% of all patients were working full-time and 24% were unemployed. Five years later, 63% were working full-time and only 11% were unemployed. Full-time employment rose even higher in the majority who became seizure-free, and unemployment in Class One patients dropped to 3% – below the national average. The psychological, social and material benefits of having a paying job, which can hardly be overestimated, are among the biggest dividends of successful treatment of seizures.

Rarely does a medical procedure offer such a clear and long-term improvement to the well-being of patients as temporal lobectomy. In the face of such encouraging findings, the researchers recommend that patients with epilepsy focused in the temporal lobe be encouraged to consider surgery as soon as the failure of drug treatment becomes apparent. Much unnecessary suffering and marginalization could be avoided and thousands of people rescued from the trap of epilepsy if this procedure were applied in more cases.

Epilepsy is a group of disorders of the brain characterized by recurring episodes of convulsive seizures, sensory disturbances, abnormal behaviour, loss of consciousness, or all of these. In all types of epilepsy, an uncontrolled electrical discharge from the nerve cells in the cerebral cortex of the brain is evident. While the cause of most types of epilepsy is unknown, it can be associated with head injury, infection, brain tumour, intoxication, or chemical imbalance.

Topiramate is a new drug that has shown promise in the treatment of epilepsy. Since preliminary evaluation has been encouraging, double-blind, placebo-controlled trials were established in an effort to better define the effectiveness, safety and appropriate dose range of topiramate for refractory partial epilepsy. The objective of this study was to evaluate a medium-to-high dose range consisting of daily dosages of 600, 800, and 1,000 mg of topiramate.

A total of 190 patients with epilepsy, aged from 18 to 68, were enrolled in the study. Over 90% of the patients had a history of complex partial seizures, and over 60% also had secondary generalized seizures. Patients were randomly assigned to one of four groups: placebo (47 patients), 600 (48 patients), 800 (48 patients), or 1,000 (47 patients) mg topiramate (Topamax) per day.

During the 18-week treatment period, the rate of reduction in average monthly seizure rates was 1% for placebo, 41% for 600 mg/day and 800 mg/day topiramate, and 38% for 1,000 mg/day topiramate. Patients who experienced a 50% or greater reduction in the frequency of seizures included 9% of those in the placebo group, 44% in the 600 mg/day topiramate group, 40% in the 800 mg/day topiramate group, and 38% in the 1,000 mg/day topiramate group. While none of the patients in the placebo group experienced improvement of 75% to 100% in the frequency of seizures, 20% of the patients given topiramate were improved to this extent. Topiramate therapy was discontinued in 16% of patients because of side effects, the most common of which were dizziness, headache, fatigue and confusion.

The results of this study indicate that topiramate is highly effective and generally well tolerated in the treatment of refractory partial epilepsy. Dosages of topiramate greater than 600 mg/day do not appear to result in significantly greater effectiveness and may result in more side effects. However, individuals who are able to tolerate higher dosages may receive additional benefit. The investigators suggest that future studies should be aimed at better characterization of the adverse effects of topiramate. Evaluations of the safety and effectiveness of smaller doses and smaller dosage increments are also indicated.

1. Would topiramate be effective in the treatment of other forms of epilepsy, or only refractory partial epilepsy?

The primary studies that have been completed and were submitted to the U.S. FDA for approval were conducted in patients with refractory partial epilepsy. Open-label studies of this medication included patients who had other types of epilepsy and anecdotal experience suggests the drug may be effective in other seizure types. There are currently ongoing studies looking at other seizure types such as generalized epilepsies and the Lennox-Gastaut Syndrome. The Lennox-Gastaut syndrome is a severe form of epilepsy typically seen in childhood and is considered one of the most difficult epileptic syndromes to treat. Results of these studies may be presented at national meetings in the next year or two.

2. Is topiramate synthetic or derived from a natural substance? How was it discovered?

Topiramate is a synthetic compound developed by the Johnson & Johnson Pharmaceutical Research Institute. Its effectiveness in epilepsy was discovered through the collaborative program of the National Institutes for Health Epilepsy Branch. The Epilepsy Branch program allows corporations to submit compounds that might be effective in epilepsy to be evaluated in a series of animal tests and compared to standard antiepileptic drugs. This program has screened thousands of compounds over the last two decades. Topiramate was one of the compounds found to be highly effective in animal models and so was moved on to testing in humans with epilepsy.

3. Are there any trials planned to compare the efficacy and safety of topiramate with other similar drugs?

Most experts in the field feel that such trials are definitely necessary in order to compare the efficacy and tolerability of these medications. Unfortunately, these comparative trials require large numbers of patients, a tremendous effort to organize, and are extremely costly. It is my understanding that several companies have preliminary plans for such comparative trials. At the present time I am not involved in any of these trials and do not believe that any comparative trials are ongoing in the United States.

4. What is known about the long-term effects of topiramate (Topamax)?

In the database submitted to the FDA consisting of approximately 3,000 patients, there did not seem to be any consistent abnormalities of the function of the liver or bone marrow as seen with some other medications. Some patients at the University of Cincinnati Epilepsy Treatment Center have been on the medication for over eight years without significant problems.

5. Has its safety in children been evaluated?

Trials evaluating topiramate’s safety and effectiveness in children are currently underway. Preliminary data are encouraging; however, we must wait for the final results of these efficacy and safety trials in order to fully determine its role in the treatment of children.

Research has come a long way in providing effective treatment for people with epilepsy, but for some, it just is not enough. Despite adequate and therapeutic doses of medication, many still continue to experience several seizures a month. But according to researchers from the University of Michigan, a drug called oxcarbazepine may provide relief to those who continue to have a type of seizure known as a partial seizure, even if they have already been through the gamut of other medications.

In their study, researchers found that oxcarbazepine, sold under the brand name of Trileptal, was safe and effective for this population. They followed 87 patients, some as young as 12 years old, who had partial seizures that remained uncontrolled despite the fact that they were on medication. The study participants were first tapered off of their regular drug regimens, and then they were divided into two treatment groups. One group received a low dose of 300mg/day and the other group a much higher dose of 2,400 mg/day of oxcarbazepine. (The drug’s manufacturer currently recommends a daily dose of 1200 mg/day.)

The results, says study author Ahmad Beydoun, M.D., associate professor of neurology and director of the Comprehensive Epilepsy Center at the University of Michigan, are encouraging and he believes that the patients responded well to this drug. In the group receiving 2400 mg/day, 12 percent remained free of seizures and almost half had a 50 percent reduction in the number of seizures they were experiencing. The results were less encouraging for those on the lower dose — none of the patients became seizure free.

Epilepsy is a neurological disorder and affects more than 2.3 million American adults and children. It is characterized by seizures, which occur when specific brain cells release high amounts of electrical energy and in turn, trigger a sudden loss of control over movement, thought or awareness.

There are many types of seizures, and experts have divided them loosely into generalized and partial seizures. The most common type is the partial seizure, which occurs when the disturbance takes place in just one area of the brain, and affects whatever physical or mental activity that particular region controls. The generalized seizure happens when a massive burst of electrical energy occurs throughout the brain at one time, causing unconsciousness, convulsions and other severe effects.

“In epilepsy drug therapy, tolerability and efficacy are often closely related,” says Beydoun. “One of the challenges in treating this disorder is the side effects associated with the standard antiepileptic drugs.” Many patients cannot control their seizures because they are unable to tolerate high enough doses of their medication. For the most part, oxcarbazepine was well tolerated by the people in the study, and the majority of them were able to reach the highest recommended dose, which may partially explain why it worked so well for them.

Some epilepsy drugs are given in combination with other drugs, while some are used alone in what is called monotherapy. This study examined the efficacy of oxcarbazepine as a monotherapy, and it has been approved by the FDA to be used alone. However, Carmel Armon, MD, a professor of medicine at Loma Linda University in California and a Fellow with the American Academy of Neurology, is not yet ready to switch his patients over to oxycarbazepine. He believes that a closer look is needed at this drug, particularly if it is going to be used as monotherapy.

The four-month trial period, he points out, was not long enough to test the long-term efficacy of oxcarbazepine. “Even though it’s very gratifying that 12 percent had a chance to go seizure free on this medicine, the study design is not such that it would tell us how long that benefit would be sustained,” he says. Often a patient may do well initially on a new drug, but then after a few months, the same problems emerge. A much longer period of time is needed to truly test the efficacy of a drug, Armon believes.

Sometimes, just a change in a medication regimen can temporarily reduce the number of seizures, Armon points out, and so the reduction in seizures seen in the study could be partially attributed to that. “It’s frequently seen that when you make a change, a small percentage of your patients will be seizure free and then relapse, ” says Armon, who specializes in treating patients with epilepsy. “And in fact, many of my patients will give me a story that every change I’ve made seems to be a change for the better, and then they broke through.”

Armon believes while the study did demonstrate some effectiveness as a monotherapy in treating partial seizures, the results were just not that striking. Only a small percentage of the patients became seizure free, and since the study followed them for just four months, it is unknown how long the effect will last.

“Based on this knowledge,” says Armon, “They may better off working with the drugs that they are currently taking, and using oxcarbazepine as an add-on or addition to their current medication regimen.”