Silvia Kochen

A double-blind controlled clinical trial of oxcarbazepine versus phenytoin in adults with previously untreated epilepsy

In the last 5 years oxcarbazepine (OXC) has been registered in many countries for use as first-line and add-on treatment for partial seizures with or without secondarily generalized seizures (PS) and generalized tonic-clonic seizures without partial onset (GTCS). Its use as monotherapy in adults with newly diagnosed epilepsy was investigated in this double-blind, randomized, parallel-group comparison with phenytoin (PHT). A total of 287 adult patients, with either PS or GTCS, were randomized. After retrospective baseline assessment, patients were randomized to OXC or PHT in a 1:1 ratio. The double-blind treatment phase was divided into two periods: a flexible titration period of 8 weeks, followed by 48 weeks of maintenance treatment. In the efficacy analyses, no statistically significant differences were found between the treatment groups. Seventy patients (59.3%) in the OXC group and 69 (58.0%) in the PHT group were seizure-free during the maintenance period. A total of 56 of the patients in the OXC group discontinued treatment prematurely (five because of tolerability reasons) compared to 61 in the PHT group (16 for tolerability reasons). The number of premature discontinuations due to adverse experiences showed a statistically significant difference in favour of OXC. There was no statistically significant difference between the groups with respect to the total number of premature discontinuations. This trial provides further support for the efficacy and safety of OXC as first-line treatment in adults with PS and GTCS. In addition, the results show that OXC has significant advantages over PHT in terms of tolerability.

Expectation and Attention in Hierarchical Auditory Prediction

Hierarchical predictive coding suggests that attention in humans emerges from increased precision in probabilistic inference, whereas expectation biases attention in favor of contextually anticipated stimuli. We test these notions within auditory perception by independently manipulating top-down expectation and attentional precision alongside bottom-up stimulus predictability. Our findings support an integrative interpretation of commonly observed electrophysiological signatures of neurodynamics, namely mismatch negativity (MMN), P300, and contingent negative variation (CNV), as manifestations along successive levels of predictive complexity. Early first-level processing indexed by the MMN was sensitive to stimulus predictability: here, attentional precision enhanced early responses, but explicit top-down expectation diminished it. This pattern was in contrast to later, second-level processing indexed by the P300: although sensitive to the degree of predictability, responses at this level were contingent on attentional engagement and in fact sharpened by top-down expectation. At the highest level, the drift of the CNV was a fine-grained marker of top-down expectation itself. Source reconstruction of high-density EEG, supported by intracranial recordings, implicated temporal and frontal regions differentially active at early and late levels. The cortical generators of the CNV suggested that it might be involved in facilitating the consolidation of context-salient stimuli into conscious perception. These results provide convergent empirical support to promising recent accounts of attention and expectation in predictive coding.

Prediction of epileptic seizures using accumulated energy in a multiresolution framework.

Records of brain electrical activity from intracranial EEG of four patients with different types of epilepsy are analyzed to predict the epileptic seizure onset. A method based on the evolution of the accumulated energy using wavelet analysis is introduced. This is an efficient method to predict epileptic seizures: from 13 preseizure signals, the seizure onset in 12 of those are predicted.

Motor-language coupling: direct evidence from early Parkinson’s disease and intracranial cortical recordings

Language and action systems are functionally coupled in the brain as demonstrated by converging evidence using Functional magnetic resonance imaging (fMRI), electroencephalography (EEG), transcranial magnetic stimulation (TMS), and lesion studies. In particular, this coupling has been demonstrated using the action-sentence compatibility effect (ACE) in which motor activity and language interact. The ACE task requires participants to listen to sentences that described actions typically performed with an open hand (e.g., clapping), a closed hand (e.g., hammering), or without any hand action (neutral); and to press a large button with either an open hand position or closed hand position immediately upon comprehending each sentence. The ACE is defined as a longer reaction time (RT) in the action-sentence incompatible conditions than in the compatible conditions. Here we investigated direct motor-language coupling in two novel and uniquely informative ways. First, we measured the behavioural ACE in patients with motor impairment (early Parkinsons disease - EPD), and second, in epileptic patients with direct electrocorticography (ECoG) recordings. In experiment 1, EPD participants with preserved general cognitive repertoire, showed a much diminished ACE relative to non-EPD volunteers. Moreover, a correlation between ACE performance and action-verb processing (kissing and dancing test - KDT) was observed. Direct cortical recordings (ECoG) in motor and language areas (experiment 2) demonstrated simultaneous bidirectional effects: motor preparation affected language processing (N400 at left inferior frontal gyrus and middle/superior temporal gyrus), and language processing affected activity in movement-related areas (motor potential at premotor and M1). Our findings show that the ACE paradigm requires ongoing integration of preserved motor and language coupling (abolished in EPD) and engages motor-temporal cortices in a bidirectional way. In addition, both experiments suggest the presence of a motor-language network which is not restricted to somatotopically defined brain areas. These results open new pathways in the fields of motor diseases, theoretical approaches to language understanding, and models of action-perception coupling.

Psychiatric disorders in patients with psychogenic non-epileptic seizures, with and without comorbid epilepsy

PURPOSE The aim of this study is to describe similarities and differences in epidemiological, psychiatric and semiologic variables between patients with psychogenic none epileptic seizures (PNES) and comorbid epilepsy (mixed PNES), and patients with PNES without comorbid epilepsy (pure PNES). RESULTS Forty-three patients with PNES diagnosed by Video-EEG were included. Twenty-four had pure PNES, and ninteen mixed PNES. Female population, age, duration of PNES, psychiatric institutionalization, psychopharmacotherapy, dissociative disorders and posttraumatic stress disorder (PTSD), were significantly higher in the pure PNES patients. Suicide attempts, antiepileptic therapy, conversive, affective and personality disorders were frequent in both groups. In the analysis of seizure semiology, the total lack of responsiveness was significantly higher in the mixed PNES group. CONCLUSIONS Pure PNES patients showed similarities and differences in the psychiatric profile, with a greater prevalence of dissociative disorders and PTSD, factors related to psychiatric severity.

Clinical Features and Prognosis of Nonepileptic Seizures in a Developing Country

Summary:  Purpose: To determine the predictive value of clinical features and medical history in patients with nonepileptic seizures (NESs).

Association study between interleukin 1β gene and epileptic disorders: a HuGe review and meta-analysis

Previous studies have examined the association of a single nucleotide polymorphism at the promoter region of interleukin 1B (IL-1β-511T) with temporal lobe epilepsy and febrile seizures susceptibility, but those studies have been inconclusive. Published studies up to March 2007 of temporal lobe epilepsy, febrile seizures and the IL-1β-511T single nucleotide polymorphism were identified by searches of Medline and Embase databases. Meta-analysis of temporal lobe epilepsy and febrile seizures case-control data were performed to assess the association of IL-1β-511T with temporal lobe epilepsy, temporal lobe epilepsy with hippocampal sclerosis, febrile seizures, and other epileptic disorders. Pooled odds ratios (OR) were estimated by means of a genetic-model-free approach. The quality of the included studies was assessed by a score. The results show a modest association (OR, 1.48; 95% confidence interval, 1.09–2.00; P = 0.01) between the IL-1β-511T polymorphism and temporal lobe epilepsy with hippocampal sclerosis.

Approximate average head models for EEG source imaging

We examine the performance of approximate models (AM) of the head in solving the EEG inverse problem. The AM are needed when the individuals MRI is not available. We simulate the electric potential distribution generated by cortical sources for a large sample of 305 subjects, and solve the inverse problem with AM. Statistical comparisons are carried out with the distribution of the localization errors. We propose several new AM. These are the average of many individual realistic MRI-based models, such as surface-based models or lead fields. We demonstrate that the lead fields of the AM should be calculated considering source moments not constrained to be normal to the cortex. We also show that the imperfect anatomical correspondence between all cortices is the most important cause of localization errors. Our average models perform better than a random individual model or the usual average model in the MNI space. We also show that a classification based on race and gender or head size before averaging does not significantly improve the results. Our average models are slightly better than an existing AM with shape guided by measured individual electrode positions, and have the advantage of not requiring such measurements. Among the studied models, the Average Lead Field seems the most convenient tool in large and systematical clinical and research studies demanding EEG source localization, when MRI are unavailable. This AM does not need a strict alignment between head models, and can therefore be easily achieved for any type of head modeling approach.

Applying time-frequency analysis to seizure EEG activity

The authors confirmed previous results about the ability to perform an EEG time-frequency analysis in a systematic way. This method gives an accurate description of the time evolution of the rhythm defined in the epileptic activity. One can generate a time series that quantifies the dynamic behavior of brain activity, independent of the EEG signal morphology. In particular, the lag correlation among these new time series gives a good picture of the information transfer process of epileptiform activity throughout the brain. The authors applied this method to intracranial EEG records of epileptic refractory patients. They conclude that the epileptic seizure could be characterized by a quasi-monofrequency activity for some of the bands. This characteristic can be used to analyze the epileptic seizure and to study the dynamic changes in its time evolution. The use of the present time-frequency analysis, together with patient clinical history and the visual assessment of the EEG, can contribute to the identification of the source of epileptic seizure activity and of its propagation within the brain. Furthermore, it yields new insights with respect to the behavior of the electrical activity during the seizure.

Prevalence and Clinical Features of Epilepsy in Argentina

Objective: To ascertain the prevalence of epilepsy in Junín, a town of 70,000–80,000 inhabitants from the Province of Buenos Aires, Argentina. Background: Some South American communities have reported extremely high prevalences of epilepsy. We investigated whether Junín would also have a high prevalence.Design/Methods: Systematic sampling was used to select 5,839 households (sampling fraction = 25%). Participating households amounted to 5,648 (97%), with 17,049 persons. A two-phase case-finding strategy was used. Phase 1 was the screening of the 17,049 persons, which was performed by trained but medically unsophisticated interviewers. Phase 2 was the neurological evaluation of the 250 persons who were screened positive for epilepsy. Diagnoses were based on defined diagnostic criteria. Results: As of January 1, 1991 (prevalence day), 106 persons had epilepsy, including 64 (60%) with active epilepsy. Among these, 9 (14%) were epilepsy cases newly diagnosed by survey neurologists, and 50 (78%) were on antiepileptic treatment at the time of the survey. Regarding the same 64 persons, seizures were generalized in 37 (58%) and partial in 24 (38%). Lifetime prevalence of epilepsy was 6.2/1,000 (6.3/1,000, age adjusted to the world standard population). Total point prevalence for active epilepsy was 3.8/1,000 (4.0 for females and 3.5 for males). In addition, prevalence peaked at the ages of 40–59 for females and 0–4 for males. Conclusions: This is one of the first community-based studies of epilepsy in Argentina, and the prevalence results provide new epidemiological data contributing to our understanding of the different prevalence rates found in Latin America.