Surgery soon after failure of drug treatment for epilepsy may lower risk of seizures

March 6, 2012, JAMA and Archives Journals

Patients with epilepsy who underwent brain surgery soon after failing to respond to drug treatment, but who also continued to receive drug therapy, had a lower risk of seizures during the 2nd year of follow-up compared to patients who received drug treatment alone, according to a study in the March 7 issue of JAMA.

"Epilepsy is a worldwide serious health concern, accounting for 1 percent of the global burden of disease, equivalent to in men and in women. The 20 percent to 40 percent of patients who have medically intractable epilepsy account for 80 percent of the cost of epilepsy. (TLE) is the most common cause of drug-resistant seizures, but it can be treated surgically," according to background information in the article. The American Academy of Neurology practice parameter recommends surgery as the treatment of choice for medically intractable TLE, but use of this treatment is delayed and underutilized. Patients who are referred for surgery have had epilepsy for an average of 22 years, more than 10 years after failure of 2 (AEDs). Because earlier surgery could prevent significant illness and , it has been recommended that a be conducted to evaluate its efficacy.

Jerome Engel Jr., M.D., Ph.D., of the University of California, Los Angeles, and colleagues conducted a study to compare outcomes of surgery for epilepsy with those of continued drug treatment. The clinical trial, performed at 16 U.S. epilepsy , included 38 participants (18 men and 20 women; age 12 years or older) who had mesial temporal lobe (a section of the brain) epilepsy (MTLE) and disabling seizures for no more than 2 consecutive years following adequate trials of 2 brand-name AEDs. Planned enrollment was 200, but the trial was halted prematurely due to slow accrual. Eligibility for anteromesial temporal resection (AMTR; surgery/removal of tissue of a section of the brain) was based on a standardized presurgical evaluation protocol. Participants were randomized to continued AED treatment (n = 23) or a standardized AMTR plus AED treatment (n = 15). In the medical group, 7 participants underwent AMTR prior to the end of follow-up and 1 participant in the surgical group never received surgery. The primary outcome measure for the study was freedom from disabling seizures during year 2 of follow-up. Other outcomes included measures on health-related quality of life (QOL) and cognitive function.

In results for the primary analysis, 0 of 23 participants in the medical group and 11 of 15 in the surgical group (73 percent) were seizure free. Analysis of only those participants who provided complete data in year 2 (or reported seizures in year 2) showed that 0 of 19 in the medical group vs. 11 of 13 in the surgical group (85 percent) were seizure free. Nine of the 11 participants in the surgical group who became free of disabling seizures never experienced a seizure after surgery; the other 2 participants last reported seizures 4 and 21 days after surgery.

"In the intention-to-treat analyses, participants in the surgical group had significantly higher increases in health-related QOL than those in the medical group at months 6, 12, and 18, but not at month 24. When excluding data obtained after surgery from participants in the medical group (n = 6), the effect of surgery on overall QOL was statistically significant at month 24," the authors write.

There were no significant treatment group differences with respect to the primary memory and nonmemory measures, although participants in the medical group tended to perform better on memory measures. A total of 13 serious adverse events (7 in the medical group and 6 in the surgical group) occurred in 9 participants (4 in the medical group, 5 in the surgical group) during the study.

"Only a small percentage of patients with medically are ever referred to an epilepsy center that offers surgery, and they are often referred too late for successful surgery to prevent serious disability. The reasons for this remain obscure. The data presented here reinforce the view that surgery soon after failure of 2 AED trials offers the best chance of preventing a lifetime of disability. The results of this study support the conclusions of the American Academy of Neurology practice parameter, namely that all patients with epilepsy should be referred to an center as soon as trials of 2 AEDs fail, and surgery should be performed if patients meet criteria for an AMTR," the researchers conclude.

In an accompanying editorial, Donald L. Schomer, M.D., of the Beth Israel Deaconess Medical Center, Harvard University, Boston, and Roger J. Lewis, M.D., Ph.D., of the Harbor-UCLA Medical Center, Torrance, and David Geffen School of Medicine at University of California, Los Angeles, write that there are several clinically important messages from this study.

"First, the early surgical approach for patients with refractory MTLE was far superior to the medical treatment when comparing seizure freedom and QOL. Because QOL measures have a high correlation with seizure freedom, this is not surprising. Second, the surgical treatment of MTLE may lead to specific memory deficits. MTLE appears to have a progressive decline in memory tasks in some patients over the long-term course. What is not known from this study is whether the surgically induced memory decline is equal to, greater than, or less than memory decline that might occur during the long-term medical management. … Third, freedom from seizures and improved QOL do not predict return to work. Employment activities did not seem to show a group difference even though measures of social engagement did show a positive effect. This matter is especially troublesome in terms of the ultimate effect of either treatment approach on the total medical and social burden and costs of MTLE. Patients with MTLE need ongoing counseling and access to work-related training whether they receive or not."

Explore further: Long-term study shows epilepsy surgery improves seizure control and quality of life

More information: JAMA. 2012;307[9]:922-930.
JAMA. 2012;307[8]:966-967.

Related Stories

Long-term study shows epilepsy surgery improves seizure control and quality of life

February 7, 2012
While epilepsy surgery is a safe and effective intervention for seizure control, medical therapy remains the more prominent treatment option for those with epilepsy. However, a new 26-year study reveals that following epilepsy ...

Brain stimulator shown to reduce 'untreatable' epileptic seizures

November 8, 2011
Brain stimulation, already approved by the U.S. Food and Drug Administration for the treatment of Parkinson's disease and essential tremor, has now been shown to offer significant relief to patients with intractable seizures ...

Surgery for epilepsy leads to around half of patients being seizure-free after 10 years

October 13, 2011
Around half of patients remain seizure free 10 years after undergoing surgery for epilepsy. However, there is scope for further improvement in presurgical assessment and surgical treatment of people with chronic epilepsy. ...

Recommended for you

Brain zaps may help curb tics of Tourette syndrome

January 16, 2018
Electric zaps can help rewire the brains of Tourette syndrome patients, effectively reducing their uncontrollable vocal and motor tics, a new study shows.

A 'touching sight': How babies' brains process touch builds foundations for learning

January 16, 2018
Touch is the first of the five senses to develop, yet scientists know far less about the baby's brain response to touch than to, say, the sight of mom's face, or the sound of her voice.

Researchers identify protein involved in cocaine addiction

January 16, 2018
Mount Sinai researchers have identified a protein produced by the immune system—granulocyte-colony stimulating factor (G-CSF)—that could be responsible for the development of cocaine addiction.

Neuroscientists suggest a model for how we gain volitional control of what we hold in our minds

January 16, 2018
Working memory is a sort of "mental sketchpad" that allows you to accomplish everyday tasks such as calling in your hungry family's takeout order and finding the bathroom you were just told "will be the third door on the ...

Brain imaging predicts language learning in deaf children

January 15, 2018
In a new international collaborative study between The Chinese University of Hong Kong and Ann & Robert H. Lurie Children's Hospital of Chicago, researchers created a machine learning algorithm that uses brain scans to predict ...

Preterm babies may suffer setbacks in auditory brain development, speech

January 15, 2018
Preterm babies born early in the third trimester of pregnancy are likely to experience delays in the development of the auditory cortex, a brain region essential to hearing and understanding sound, a new study reveals. Such ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.