Oxcarbazepine (OXC) has been licensed as monotherapy and add-on treatment in epilepsy patients with partial seizures with or without secondarily generalized seizures (PS) and generalized tonic-clonic seizures without partial onset (GTCS).... more
Oxcarbazepine (OXC) has been licensed as monotherapy and add-on treatment in epilepsy patients with 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 ...
To assess the activity of brivaracetam, a novel SV2A ligand, in the photosensitivity model as a proof-of-principle of efficacy in patients with epilepsy. A subject-blind placebo-controlled study in patients with photosensitive epilepsy... more
To assess the activity of brivaracetam, a novel SV2A ligand, in the photosensitivity model as a proof-of-principle of efficacy in patients with epilepsy. A subject-blind placebo-controlled study in patients with photosensitive epilepsy was performed to investigate the effect of single-dose brivaracetam (10, 20, 40, or 80 mg) on photosensitive responses. Each patient was exposed to intermittent photic stimulation that evoked a generalized photoparoxysmal EEG response. Individual standard photosensitivity ranges (SPRs) were recorded post-placebo (day -1) and post-brivaracetam until return to baseline (day 1 to 3). Plasma concentrations of brivaracetam and any concomitant antiepileptic drugs were determined. Of the 18 evaluable patients, none achieved SPR abolishment post-placebo, whereas 14 (78%) achieved complete abolishment post-brivaracetam. Decrease in SPR was seen in 8 patients (44%) post-placebo compared to 17 (94%) post-brivaracetam. Duration of response was twice as long post-brivaracetam 80 mg (59.5 hours) compared with lower doses, although the overall effect was not dose-dependent. Time to maximal photosensitive response was dose-related with the shortest time interval observed at the highest dose (0.5 hours post-brivaracetam 80 mg). The area under the effect curve (SPR change from pre-dose vs time) appeared linearly correlated with the area under the plasma concentration curve. Brivaracetam was well tolerated. The most common adverse events were dizziness and somnolence. Our findings show that brivaracetam clearly suppresses generalized photoparoxysmal EEG response. As such, investigations of the antiepileptic properties and tolerability of brivaracetam are warranted in further clinical studies of patients with epilepsy.
- by Dominique Parain and +1
- •
- Cognitive Science, Neurology, Adolescent, Humans
The reliability of frontal and temporal fMRI activations for the determination of hemisphere language dominance was evaluated in comparison with intracarotid amytal testing (IAT). Twenty-two patients were studied by IAT (bilateral in 13,... more
The reliability of frontal and temporal fMRI activations for the determination of hemisphere language dominance was evaluated in comparison with intracarotid amytal testing (IAT). Twenty-two patients were studied by IAT (bilateral in 13, unilateral in 9 patients) and fMRI using a paradigm requiring semantic decisions. Global and regional (frontal and temporoparietal) lateralisation indices (LI) were calculated from the number of activated (r>0.4) voxels in both hemispheres. Frontolateral activations associated with the language task were seen in all patients, temporoparietal activations in 20 of 22. Regional LI corresponded better with IAT results than global LI. Frontolateral LI were consistent with IAT in all patients with bilateral IAT (including three patients with right dominant and one patient with bilateral language representation) and were not conflicting in any of the patients with unilateral IAT. Temporoparietal LI were discordant with IAT in two patients with atypical language representation. In the determination of hemisphere dominance for language, regional analysis of fMRI activation is superior to global analysis. In cases with clear-cut fMRI lateralisation, i.e. consistent lateralised activation of frontal and temporoparietal language zones, IAT may be unnecessary. FMRI should be performed prior to IAT in all patients going to be operated in brain regions potentially involved in language.
Epilepsies are amongst the most frequent chronic neurological conditions. Patients suffer from spontaneously recurring seizures because of sudden extensive electrical gray matter discharges. Although the current drug therapy allows many... more
Epilepsies are amongst the most frequent chronic neurological conditions. Patients suffer from spontaneously recurring seizures because of sudden extensive electrical gray matter discharges. Although the current drug therapy allows many patients at least some degree of a satisfying course of the disease, a substantial number of patients remain without adequate seizure control. Reasons are either refractoriness to anticonvulsant drugs or intolerable drug-related side effects. Epilepsy surgery should be considered in these cases as possible treatment option. Nevertheless, a considerable rate of patients will not be suitable candidates or continue to have seizures despite surgery. Therefore there is a substantial need for better antiepileptic drugs. The aim of this review is to highlight currently emerging different treatment approaches which may ameliorate the perspectives of patients with difficult-to-treat epilepsies.
- by Bernhard Steinhoff and +1
- •
- Epilepsy, Humans, Animals, Clinical Sciences
7 Zusammenfassung Lacosa-mid (LCM, R-2-Acetamido-N-ben-zyl-3-methoxypropionamid) ge-hört zu der Gruppe der funktionali-sierten Aminosäuren. In tierexperi-mentellen Studien erwies sich LCM als ein wirksames Medikament ge-gen fokale Anfälle... more
7 Zusammenfassung Lacosa-mid (LCM, R-2-Acetamido-N-ben-zyl-3-methoxypropionamid) ge-hört zu der Gruppe der funktionali-sierten Aminosäuren. In tierexperi-mentellen Studien erwies sich LCM als ein wirksames Medikament ge-gen fokale Anfälle und beeinflusst ...
- by Bernhard Steinhoff and +1
- •
- Enzyme
New and improved anti-epileptic drugs (AEDs) have made the concept of choice, according to the individual prognosis and probable response to specific regimens, increasingly feasible. Inter-individual variability in syndrome severity and... more
New and improved anti-epileptic drugs (AEDs) have made the concept of choice, according to the individual prognosis and probable response to specific regimens, increasingly feasible. Inter-individual variability in syndrome severity and complexity make individualization necessary. We propose three categories of disorder control according to the individual objectives of the patient: (1) seizure control, (2) epilepsy control and ultimately, (3) "epilepsy cure"; the latter remaining a largely idealistic target today. An AED is likely to be successful if it exhibits "optimal" characteristics, such as drug efficacy, tolerability, pharmacokinetics, interactions and cost-effectiveness. This review discusses the "optimal" characteristics of add-on AEDs, which, in addition to seizure control, will contribute to the achievement of epilepsy control and therefore address the currently unmet clinical needs of epilepsy treatment.
Historically, seizure semiology was the main feature in the differential diagnosis of epileptic syndromes. With the development of clinical EEG, the definition of electroclinical complexes became an essential tool to define epileptic... more
Historically, seizure semiology was the main feature in the differential diagnosis of epileptic syndromes. With the development of clinical EEG, the definition of electroclinical complexes became an essential tool to define epileptic syndromes, particularly focal epileptic syndromes. Modern advances in diagnostic technology, particularly in neuroimaging and molecular biology, now permit better definitions of epileptic syndromes. At the same time detailed studies showed that there does not necessarily exist a one-to-one relationship between epileptic seizures or electroclinical complexes and epileptic syndromes. These developments call for the reintroduction of an epileptic seizure classification based exclusively on clinical semiology, similar to the seizure classifications which were used by neurologists before the introduction of the modern diagnostic methods. This classification of epileptic seizures should always be complemented by an epileptic syndrome classification based on all the available clinical information (clinical history, neurological exam, ictal semiology, EEG, anatomical and functional neuroimaging, etc.). Such an approach is more consistent with mainstream clinical neurology and would avoid the current confusion between the classification of epileptic seizures (which in the International Seizure Classification is actually a classification of electroclinical complexes) and the classification of epileptic syndromes.
Deletions at 16p13.11 are associated with schizophrenia, mental retardation, and most recently idiopathic generalized epilepsy. To evaluate the role of 16p13.11 deletions, as well as other structural variation, in epilepsy disorders, we... more
Deletions at 16p13.11 are associated with schizophrenia, mental retardation, and most recently idiopathic generalized epilepsy. To evaluate the role of 16p13.11 deletions, as well as other structural variation, in epilepsy disorders, we used genome-wide screens to identify copy number variation in 3812 patients with a diverse spectrum of epilepsy syndromes and in 1299 neurologically-normal controls. Large deletions (> 100 kb) at 16p13.11 were observed in 23 patients, whereas no control had a deletion greater than 16 kb. Patients, even those with identically sized 16p13.11 deletions, presented with highly variable epilepsy phenotypes. For a subset of patients with a 16p13.11 deletion, we show a consistent reduction of expression for included genes, suggesting that haploinsufficiency might contribute to pathogenicity. We also investigated another possible mechanism of pathogenicity by using hybridization-based capture and next-generation sequencing of the homologous chromosome for ten 16p13.11-deletion patients to look for unmasked recessive mutations. Follow-up genotyping of suggestive polymorphisms failed to identify any convincing recessive-acting mutations in the homologous interval corresponding to the deletion. The observation that two of the 16p13.11 deletions were larger than 2 Mb in size led us to screen for other large deletions. We found 12 additional genomic regions harboring deletions > 2 Mb in epilepsy patients, and none in controls. Additional evaluation is needed to characterize the role of these exceedingly large, non-locus-specific deletions in epilepsy. Collectively, these data implicate 16p13.11 and possibly other large deletions as risk factors for a wide range of epilepsy disorders, and they appear to point toward haploinsufficiency as a contributor to the pathogenicity of deletions.
In 1996, our group published objective electroencephalogram (EEG) criteria to define periodic sharp-wave complexes (PSWCs) suggestive for Creutzfeldt-Jakob disease (CJD). These criteria have since then been strictly applied in all cases... more
In 1996, our group published objective electroencephalogram (EEG) criteria to define periodic sharp-wave complexes (PSWCs) suggestive for Creutzfeldt-Jakob disease (CJD). These criteria have since then been strictly applied in all cases reported to us as possible CJD in the course of the German CJD surveillance study. Furthermore, EEG analysis of the records was performed without any additional information on complementary clinical and laboratory data. In this study, we investigated sensitivity, specificity, and the predictive values of these EEG criteria exclusively in cases in which autopsy confirmed (n=150) or excluded (n=56) CJD. EEG criteria were positive in 64% (n=96) of the CJD cases and falsely positive in 9% (n=5) of other dementias. The resulting figures for sensitivity, specificity, and positive and negative predictive values were 64%, 91%, 95%, and 49%, respectively. In the falsely positive cases, Alzheimer's disease (n=4) and vascular dementia (n=1) were the underlying diseases. However, only in one of these five cases both clinical and EEG data would have led to the false-positive result to diagnose probable CJD. These data prove the high diagnostic value of our objective EEG criteria in CJD.
... Processing in Autism Estate Sokhadze Joshua Baruth Allan Tasman Mehreen Mansoor Rajesh Ramaswamy Lonnie Sears Grace Mathai Ayman El-Baz Manuel F. Casanova Published online: 26 November 2009 © Springer Science+Business... more
... Processing in Autism Estate Sokhadze Joshua Baruth Allan Tasman Mehreen Mansoor Rajesh Ramaswamy Lonnie Sears Grace Mathai Ayman El-Baz Manuel F. Casanova Published online: 26 November 2009 © Springer Science+Business Media, LLC 2009 ...