News From The Annual Meeting of the American Epilepsy Society, San Diego, December 1-5, 2006

February 1, 2007

Patients with established epilepsy may have a 48% chance of becoming seizure-free, according to research by Nathan B. Fountain, MD, associate professor of neurology, and colleagues at the University of Virginia (UVA), Charlottesville. Although the rate of freedom from seizure is unknown except for in a few specific epilepsy syndromes, the authors hypothesized that the rate may be higher than expected.

RATE OF FREEDOM FROM SEIZURE MAY BE HIGHER THANEXPECTED IN PATIENTS WITH EPILEPSY. Patients withestablished epilepsy may have a 48% chance of becomingseizure-free, according to research by NathanB. Fountain, MD, associate professor of neurology, andcolleagues at the University of Virginia (UVA), Charlottesville.Although the rate of freedom from seizureis unknown except for in a few specific epilepsy syndromes,the authors hypothesized that the rate may behigher than expected.

The researchers prospectively collected data fromestablished and new patients with definite epilepsywho were older than 5 years and seen in the UVAEpilepsy Clinic.

Freedom from seizure was defined as no seizuresfor at least 6 months in patients who previously hadhad 3 or more seizures. Baseline seizure frequency forthese patients was as follows: 15% had more than 15per month, 56% had 1 to 15 per month, and 21% hadfewer than 1 per month.

Of these 988 patients, 243 (25%) were seizure-freeby the end of the study; an additional 231 (23%) hadpreviously achieved freedom from seizures, and 514(52%) continued to experience seizures. Among thosepatients who became seizure-free, mean follow-uptime was 24.5 months and mean duration of freedomfrom seizure was 20.9 months.

Patients with generalized seizures or idiopathicgeneralized and idiopathic localization-related epilepsywere more likely to become seizure-free. The researchersnoted, however, that some seizure freedomcan occur in any patient regardless of seizure type.

GLUCOSE METABOLISM MAY EFFECT DURATION OF TEMPORALLOBE EPILEPSY. Asymmetry of glucose metabolismin the temporal lobes of persons with temporallobe epilepsy (TLE) may be associated with the durationof epilepsy, according to research presented byCigdem I. Akman, MD, assistant professor in clinicalneurology and pediatrics at Columbia University inNew York City. Akman and colleagues used 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography(18FDG/PET) to assess interictal functioning in TLE.

Fifty patients with pharmacologically resistant TLEreceived 18FDG/PET as part of a presurgical evaluation.Twenty-six patients had right TLE and 24 had leftTLE. The mean patient age at the time of PET scan was37 years in both groups, and the duration of epilepsy,age at onset, number of medications, and level of educationwere similar for both groups.

Of the patients with right TLE, 30.8% had ipsilateralhypometabolism in the epileptic temporal lobe,11.5% had bitemporal hypometabolism, and 23.1%had mesial temporal sclerosis. Of the patients with leftTLE, 20.8% had ipsilateral hypometabolism in theepileptic temporal lobe, 8.3% had bitemporal hypometabolism,and 37.5% had mesial temporal sclerosis.

The authors concluded that the relative increase inglucose metabolism contralateral to the epileptogenictemporal lobe shows that compensatory changes inthe more normal hemisphere may develop.

LAMOTRIGINE SHOWN TO BE MOST EFFECTIVE TREATMENTFOR PARTIAL-ONSET SEIZURES. Lamotrigine should beconsidered the treatment of choice for patients withpartial-onset seizures, according to results of the Standardand New Antiepileptic Drugs trial, led by AnthonyMarson, MD, senior lecturer in neurology at theUniversity of Liverpool, United Kingdom.

While carbamazepine is the most widely acceptedtreatment for patients with partial-onset seizures, theresearchers concluded that lamotrigine has similarlong-term effectiveness and is better tolerated.Adults and children in the unblinded, randomizedcontrolled trial who had been originally treated withcarbamazepine were randomly assigned to receive carbamazepine,gabapentin, lamotrigine, oxcarbazepine,or topiramate. At the start of the trial, 87% of patientswere classified as having symptomatic or cryptogenicpartial epilepsy. Outcomes were time to treatment failureand time to 1-year remission.

Researchers found that in the time-to-treatmentfailuregroup, lamotrigine was significantly superiorto the other treatments. In the time-to-1-year-remissiongroup, gabapentin was significantly inferior tocarbamazepine, lamotrigine, and oxcarbazepine. Inthis group, there was no significant difference betweencarbamazepine and lamotrigine.

WOMEN'S ISSUES IN EPILEPSYIN UTERO VALPROATE USE MAY HINDER CHILDREN'SMENTAL DEVELOPMENT. Valproate poses a greater riskfor behavioral teratogenesis in the unborn child thando other antiepileptic drugs (AEDs), according to researchby Kimford J. Meador, MD, professor of neurologyat the University of Florida, Gainesville, andcolleagues. The results of this study, conducted by theNeurodevelopmental Effects of Antiepileptic Drugs(NEAD) study group, were based on observations of2-year-old children of women with epilepsy who hadbeen on monotherapy with carbamazepine, lamotrigine,phenytoin, or valproate while pregnant.

The interim results of the NEAD study, which willmonitor the neurologic development of the study participantsuntil they are 6 years old, showed that of the166 children tested, mean Mental Development Index(MDI) scores were 94 for children exposed to carbamazepinein utero, 97 for lamotrigine, 90 for phenytoin,and 85 for valproate. The percentages of childrenwith an MDI score lower than 70 for each AED were12% for carbamazepine, 11% for lamotrigine, 13% forphenytoin, and 25% for valproate.

The authors said that these findings are supportedby previous studies that have shown that exposure inutero to valproate is more likely to impair cognitivedevelopment than are other commonly used AEDs.

PREMATURE OVARIAN FAILURE OCCURS FREQUENTLY INWOMEN WITH EPILEPSY. Premature ovarian failure--menopause by age 40 years--occurs at a markedlyhigher rate in women with epilepsy (4.8%) than inwomen in the general population (1%), reported TeresaA. Tran, MD, adjunct associate professor of neurologyat the University of Minnesota, Minneapolis.Tran's team surveyed the menstrual history andmenopause symptoms of all women aged 40 to 60years at their clinic since 2002. Study exclusion criteriaincluded having nonepileptic events, current use ofhormone contraceptives, and surgical menopause.

Of the 269 patients in the study, medical recordswere reviewed for age at seizure onset, epilepsy diagnosis,seizure history, antiepileptic drug history, concomitantmedication history, endocrinologic disorders,weight, and height. Patient menopause statuswas self-reported and defined as not having a menstrualperiod in 12 months or more.

Thirteen women (4.8%) were postmenopausal byage 40 years (mean, 35.8 years; range, 25 to 40 years).Of these patients, none had a known endocrinologicdisorder; 12 had localization-related epilepsy; age atseizure onset ranged from younger than 1 year to 20years (mean, 8.5 years; median, 5 years); and 9 wereexperiencing at least 1 seizure per year (range, fewerthan 1 per month to 17 per month). According to Tran,these results raise concerns that poorly controlledepilepsy disrupts the hypothalamic-pituitary-ovarianaxis and reproductive function.

SEIZURE CLUSTERS OCCUR OFTEN IN WOMEN WITHANOVULATORY CYCLES. The majority (53.3%) of womenwith localization-related epilepsy have clusteredseizure distributions, and clustering may be significantlymore common with anovulatory than with ovulatorycycles, according to the preliminary findings ofa prospective study presented by Kristen M. Fowler,MA, study coordinator at the Beth Israel DeaconessMedical Center, Harvard Neuroendocrine Unit, Boston,and colleagues. According to the authors, previousstudies have shown that seizures in women maynot occur randomly but may cluster.

The research team collected data on 100 womenaged 13 to 45 years with localization-related epilepsywho were participating in a multicenter investigationof supplemental progesterone therapy for the treatmentof intractable seizures. Data were recorded onseizures and menses during 3 baseline menstrual cycles.Midluteal progesterone levels of 5 ng/mL orhigher were used to identify ovulatory cycles.

Seventy-five patients (75%) had 10 or more seizuresduring the 3-month observation period. Of these, 29(38.7%) had random seizure distributions. Of the 46(61.3%) patients who had nonrandom distributions, 6(13.0%) had even distributions, and 40 (87.0%) hadclustered distributions. Researchers reported that clusteringwas significant in those patients with anovulatorycycles compared with those with ovulatory cycles.There was no evidence of clustering related to ageof study participants, age of participants at epilepsyonset, duration of epilepsy, EEG laterality, or antiepilepticdrug therapy.