19. Placebo responses to AEDs

A.B. Guekht 1, A.D. Korczyn 2, I.B. Bondareva 3, E.I. Gusev 1, 1 Department of Neurologyand Neurosurgery, Russian State Medical University, Moscow, Russia, 2 Sieratzki Chair ofNeurology, Tel-Aviv University, Ramat Aviv, Israel, 3 The Research Institute of Physical –Chemical Medicine, Moscow, Russia

Objective: Randomized, double-blind, placebo-controlled trials arethe ‘‘gold standard’’ for evaluation of treatment effects of new AEDs.The use of placebos requires understanding of their effects. The pla-cebo effect is a complex of several different components, such asregression towards the mean, effect of being a research participant(the Hawthorne effect), and receiving an apparently therapeutic inter-vention (the placebo effect proper), which are difficult to separatefrom each other. However, we have found in the literature only afew attempts to assess the magnitude of the placebo effect in epilepsy.

Methods: The meta-analysis of published randomized controlledtrials (RCT) of antiepileptic drugs (AEDs) in adults with focal drug-resistant epilepsy was performed in order to estimate a mean pla-cebo effect, to evaluate variability in placebo response rates, toinvestigate associations between placebo effect rates and study char-acteristics, and to determine whether there were changes in placeboresponse rates over recent years in RCTs (so called ‘‘placebo drift’’).

Results: One hundred and ninety-eight potentially appropriatestudies were identified after MEDLINE search and carefully re-viewed. Twenty-seven RCT (with 5662 randomized patients, includ-ing 1887 patients in placebo arms) were included in the meta-analysis. A random effects meta-analytic model estimated thepooled placebo response at 12.5% (95% CI 10.03–14.94%). A statisti-cally significant correlation between baseline median seizure fre-quency and placebo response rates was not observed. ‘‘Placebodrift’’ was not considered statistically significant.

Conclusions: Our results showed the existence of a marked pla-cebo effect in most RCTs, even though the target effect was quiterestrictive. Further studies evaluating factors accounting for a pla-cebo response are needed.

doi:10.1016/j.yebeh.2010.01.044

Higher cortical function in epilepsy

20. The WADA test: Lessons on language dominance and changeof clinical indication with improvements in the diagnosis andsurgical treatment of epilepsy

C. Helmstaedter, University Clinic Bonn, Epileptology, Bonn, Germany

WADA tests are traditionally performed before brain surgery inorder to prevent postoperative aphasia or global amnesia. Whilethe WADA test still appears to be the gold standard for the detaileddescription of graded or dissociated language dominance patternsand for reversible simulation of lateralized hemispheric damage,its clinical indication has dramatically changed.

At the Bonn epilepsy center, the percentage of surgical candidatesundergoing WADA tests has dropped from up to 46% between 1989and 1996 to 12–15% between 1997 and 2006. This reflects the trendto more individual and selective surgery as well as the expandingknowledge about clinical markers for atypical dominance (left sidedepilepsy, lesions in or adjacent to language cortex, developmentallesions, onset of epilepsy before puberty, left handedness, female gen-der, neuropsychological hints for crowding, non-corresponding ictal/postictal impairments). Now, fMRI has become a tool for a first orien-tation. The value of functional transcranial doppler sonography (fTCD)is currently under evaluation. The language WADA, however, is stillperformed in candidates for callosotomy, hemispherectomy, and

when surgery close to or within presumed eloquent cortex is planned.Additional electro-cortical language mapping via subdural electrodesor during awake surgery helps to delineate the individual resectionborders. As for memory, no amnesic syndrome has ever been predictedfrom the WADA test. Predictions of memory outcome by the WADAtest are debatable but do not justify WADA tests in every patient. Aselective WADA test would allow memory testing with preservedlanguage but incurs an increased risk of brain stem infarcts and welack reference data for its interpretation. Memory outcome can grosslybe predicted by neuropsychological regression methods as well.

In summary, the era of the WADA test as a standard procedure isending and the method has currently very limited indications. Inselected cases, however, the WADA test still represents a comparablysafe and valuable tool for determination of language dominance.

doi:10.1016/j.yebeh.2010.01.045

21. Epilepsy and language: What do we know? What do we wantto know?

William Davis Gaillard, Children’s National, Neuroscience, Washington DC, USA

Epilepsy is associated with atypical representation of languagedominance. Some studies find that language is preserved when atyp-ical language is present, others find that the re-organization of lan-guage representation is accompanied by some loss in languagefunction. fMRI and electro-cortical stimulation studies find thereare some areas common to all aspects of language processing butother regions appear specific to the nature of the items tested (e.g.object naming vs. auditory response naming). fMRI studies provideinsights to inter-hemispheric and intra-hemispheric re-organizationof language and the developmental constraints of neural plasticity.30% of chronic focal epilepsy patients have atypical language domi-nance; 7% of normal control populations have atypical language dom-inance. Different etiologies are associated with different frequenciesof atypical language. Of all factors, age is the most important; nearlyall atypical language is associated with epilepsy onset or brain injurybefore age six years. Current evidence suggests atypical language isco-morbid rather than driven by epilepsy. A number of studies usingdifferent means find that when atypical language exists, activation isfound in right hemisphere homologues of Broca’s and Wernicke’sareas. Studies that seek to examine intra-hemispheric re-organiza-tion of language find modest evidence for activation around marginsof known language processing areas, or greater activation of areasknown to be involved in the distributed network for language. Resec-tion of language dominant temporal lobe (even avoiding ‘‘activatedareas’’) is associated with some decrease in language measures, andis linked to dominant verbal hippocampus. It is unknown to whatextent resection of anterior temporal lobe is associated with specificdeficits in language processing suggested by normal studies ofsemantic processing found in anterior temporal lobe. The effect ofdisrupting the several long tracts that connect temporal languageprocessing areas and frontal regions is also not well understood.

doi:10.1016/j.yebeh.2010.01.046

22. The syndrome of transient epileptic amnesia (TEA)

Adam Zeman, Cognitive and Behavioural Neurology, Peninsula Medical School, Exeter, UK

Since Hughlings–Jackson’s celebrated description of the case ofDr. Z, a number of authors have described patients in whom themain manifestation of temporal lobe epilepsy is a brief period of

Abstracts / Epilepsy & Behavior 17 (2010) 579–620 585