Visual phenomena and anatomo-electro-clinical correlations in occipital lobe seizures.

BACKGROUND: Occipital lobe seizure are underrepresented in epilepsy surgery cases series. This may reflect the fear for post-surgical functional deficits but also the doubt about the ability of anatomo-electro-clinical correlations to localize precisely the epileptogenic zone in occipital lobe seizure. METHODS: In this expert opinion paper, we review first the general clinical characteristics of occipital lobe seizures, describe the repertoire of visual phenomena and oculo-motor signes in occipital seizures, describe inter-ictal and ictal EEG and finally the possible schemes of epileptogenic zone organization. RESULTS: Visual and oculo-motor semiology points towards occipital onset seizures but is neither pathognomonic nor constant. Eyes version and unilateral ictal discharge have a strong lateralizing value but inter-ictal spikes as well as eyes version can be falsely lateralizing. CONCLUSION: Although visual and oculo-motor phenomena are characteristic of occipital lobe seizures, they may be discrete, overlooked and should therefore be carefully assessed. There are no clear electro-clinical correlations of a sublobar organization of occipital seizures but the clinical pattern of propagation might help to differentiate complex occipito-temporal from occipito-parietal initial epileptogenic network.

Medullary thyroid cancer outcomes in patients with undetectable versus normalized postoperative calcitonin levels.

BACKGROUND: Calcitonin (Ct) is a sensitive diagnostic biomarker and one of the most important prognostic factors in medullary thyroid cancer (MTC). This study aimed to evaluate progression-free survival and recurrence rates of MTC associated with undetectable compared with normalized serum Ct levels after surgery. METHODS: This retrospective observational study included patients operated for MTC at the Digestive and Endocrine Surgery Department of Lyon Sud Hospital Centre between 2000 and 2019. Clinical and pathological factors were correlated with postoperative Ct concentrations. Undetectable and normalized Ct concentrations were defined as below 2 pg/ml and 2-10 pg/ml respectively. RESULTS: Overall, 176 patients were treated for MTC, and 127 were considered biochemically cured after surgery. Of these, 24 and 103 had normalized and undetectable Ct concentrations respectively. Patients with Ct level normalization had a 25 per cent risk of disease recurrence, compared with 3 per cent in patients with undetectable Ct levels after surgery. The presence of metastasis in two or more compartments was predictive of failure to achieve undetectable Ct concentrations after surgery and an increased risk of recurrence. CONCLUSION: Among patients with biochemically cured MTC, those with undetectable or normalized Ct concentrations after surgery had different risks of recurrence. Simply assessing postoperative Ct normalization can be falsely reassuring, and long-term follow-up is needed. LAY SUMMARY: Calcitonin (Ct) is a sensitive diagnostic biomarker and one of the most important prognostic factors for medullary thyroid cancer outcomes; however, the significance of postoperative Ct levels remains controversial. This study evaluated the differences between normal and undetectable postoperative Ct levels in patients who had undergone surgical treatment for medullary thyroid cancer. Patients who experienced postoperative Ct level normalization had a higher risk of disease recurrence than those with undetectable Ct levels after surgery.

Calcitonin (Ct) is a sensitive diagnostic biomarker and one of the most important prognostic factors for medullary thyroid cancer outcomes; however, the significance of postoperative Ct levels remains controversial. This study evaluated the differences between normal and undetectable postoperative Ct levels in patients who had undergone surgical treatment for medullary thyroid cancer. Patients who experienced postoperative Ct level normalization had a higher risk of disease recurrence than those with undetectable Ct levels after surgery.

Long-term cognitive outcomes in patient with epilepsy.

In contrast to short-term cognitive outcomes, long-term cognitive outcomes (over 5 years) has been scarcely assessed so far. Yet, predicting long-term outcomes at any time point of the epilepsy, from initial diagnosis, to medically intractability is very important for therapeutic decision-making, patient information, and orientation. Assessing long-term cognitive outcomes in patients with epilepsy would ideally require longitudinal studies and a comparison with a healthy controls group. This issue has been addressed extensively, but with controversial results. However, there is a general consensus about the fact that cognitive outcome is not the same in all groups of patients with epilepsy. Possible prognostic factors include age at onset, duration of epilepsy, syndrome and etiology, seizure outcome and therapeutics. The multiplicity of factors makes it very difficult to assess their relative weight in individuals. Although long-term cognitive outcome studies are scarce, this issue has been specifically studied in newly diagnosed epilepsies and in focal drug-resistant epilepsies. In the first clinical setting, i.e. newly diagnosed epilepsy, it appears that cognitive deficits are already present at epilepsy onset in a significant proportion of patients but seem to remain stable over time. In focal drug-resistant epilepsies, cognitive deficits (mainly verbal memory) were generally shown to remain stable provided that seizures were controlled either by medication or by surgery. Beyond the possible correlation between seizure and cognitive outcome, no causal link however has been demonstrated between these two important outcomes.

Attention disorders in adults with epilepsy. Determinants and therapeutic strategies.

Cognitive consequences in epilepsy are often described in the following domains: verbal memory, language, executive functions, and attention. Attention is involved in all cognitive activities, and attention disorders (AD) are reported in patients with various neurological diseases. This paper proposes to define the concept of AD and its assessment, to consider their determinants in epilepsy and potential therapies (drug or not). ADs are reported in new onset epilepsy, generalized epilepsy of presumed genetic origin, and in focal epilepsy. In focal epilepsy, alertness and divided attention impairment are observed and seem to improve after successful curative surgery. Additional studies are needed to assess the prevalence and nature of AD related to status epilepticus. In the field of therapeutic strategies, anti-epileptic drugs show an impact on AD. Effects of antidepressive drug therapy are not reported, as well as psychotherapy. Cognitive rehabilitation on AD is a promising therapeutic intervention but specific studies are needed to assess its efficacy.

Brain molecular imaging in pharmacoresistant focal epilepsy: Current practice and perspectives.

This review aims to synthesize all the available data on brain molecular imaging, such as single-photon emission computed tomography (SPECT) and interictal fluorodeoxyglucose positron emission tomography (FDG-PET), in focal epilepsies. SPECT imaging is able to measure regional cerebral blood flow and its major innovation remains its ictal imaging value. On the other hand, FDG-PET, which has higher spatial resolution and lower background activity than SPECT, enables glycolytic metabolism to be identified in interictal states. Therefore, interictal FDG-PET has greater sensitivity than interictal SPECT, especially in temporal lobe epilepsies (TLEs). Thus, 18F-FDG-PET is a necessary step in the presurgical evaluation of TLEs, but also of extratemporal epilepsies (ETEs), contributing to >30% of the decision to undertake surgery. In addition, FDG-PET has particular diagnostic value in focal epilepsies showing normal magnetic resonance imaging (MRI). PET also has good prognostic value for post-surgical outcomes as well as cognitive impairment, especially in cases where the hypometabolism extent is limited. Moreover, the notion of an epileptic network is well highlighted by functional PET imaging, allowing better understanding of the pathological substrates of these disorders. Future development of quantitative analysis software and of novel radiotracers and cameras will certainly enhance its clinical usefulness.

SEEG dipole source localization based on an empirical Bayesian approach taking into account forward model uncertainties.

Electromagnetic brain source localization consists in the inversion of a forward model based on a limited number of potential measurements. A wide range of methods has been developed to regularize this severely ill-posed problem and to reduce the solution space, imposing spatial smoothness, anatomical constraint or sparsity of the activated source map. This last criteria, based on physiological assumptions stating that in some particular events (e.g., epileptic spikes, evoked potential) few focal area of the brain are simultaneously actives, has gained more and more interest. Bayesian approaches have the ability to provide sparse solutions under adequate parametrization, and bring a convenient framework for the introduction of priors in the form of probabilistic density functions. However the quality of the forward model is rarely questioned while this parameter has undoubtedly a great influence on the solution. Its construction suffers from numerous approximation and uncertainties, even when using realistic numerical models. In addition, it often encodes a coarse sampling of the continuous solution space due to the computational burden its inversion implies. In this work we propose an empirical Bayesian approach to take into account the uncertainties of the forward model by allowing constrained variations around a prior physical model, in the particular context of SEEG measurements. We demonstrate on simulations that the method enhance the accuracy of the source time-course estimation as well as the sparsity of the resulting source map. Results on real signals prove the applicability of the method in real contexts.

FT-IR and NMR structural markers for thiazole-based γ-peptide foldamers.

Nuclear magnetic resonance (NMR) spectroscopy has been established as a potent method for the determination of foldamer structures in solution. However, the NMR techniques could be limited by averaging, so additional experimental techniques are often needed to fully endorse the folding properties of a sequence. We have recently demonstrated that oligo-γ-peptides composed of 4-amino(methyl)-1,3-thiazole-5-carboxylic acids (ATCs) adopt an original helical fold stabilized by hydrogen bonds forming C9 pseudocycles. The main objective of the present work is to reinvestigate the folding of ATC oligomer 1 in order to identify reliable FT-IR and NMR structural markers that are of value for tracking the degree of organization of ATC-based peptides.

Evaluating dipolar source localization feasibility from intracerebral SEEG recordings.

Stereo-electroencephalography (SEEG) is considered as the golden standard for exploring targeted structures during pre-surgical evaluation in drug-resistant partial epilepsy. The depth electrodes, inserted in the brain, consist of several collinear measuring contacts (sensors). Clinical routine analysis of SEEG signals is performed on bipolar montage, providing a focal view of the explored structures, thus eliminating activities of distant sources that propagate through the brain volume. We propose in this paper to exploit the common reference SEEG signals. In this case, the volume propagation information is preserved and electrical source localization (ESL) approaches can be proposed. Current ESL approaches used to localize and estimate the activity of the neural generators are mainly based on surface EEG/MEG signals, but very few studies exist on real SEEG recordings, and the case of equivalent current dipole source localization has not been explored yet in this context. In this study, we investigate the influence of volume conduction model, spatial configuration of SEEG sensors and level of noise on the ESL accuracy, using a realistic simulation setup. Localizations on real SEEG signals recorded during intracerebral electrical stimulations (ICS, known sources) as well as on epileptic interictal spikes are carried out. Our results show that, under certain conditions, a straightforward approach based on an equivalent current dipole model for the source and on simple analytical volume conduction models yields sufficiently precise solutions (below 10mm) of the localization problem. Thus, electrical source imaging using SEEG signals is a promising tool for distant brain source investigation and might be used as a complement to routine visual interpretations.

RANTES/CCL5-induced pro-angiogenic effects depend on CCR1, CCR5 and glycosaminoglycans.

Atherosclerosis involves angiogenesis and inflammation with the ability of endothelial cells and monocytes to respond to chemokines. We addressed here by in vitro and in vivo approaches, the role of the chemokine Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES)/CCL5 on angiogenesis through its receptors CCR1, CCR5, syndecan-1 (SDC-1), syndecan-4 (SDC-4) and CD-44. Our data demonstrate that RANTES/CCL5 is pro-angiogenic in a rat subcutaneous model. This RANTES/CCL5-activity may be related to the in vitro promotion of endothelial cell migration, spreading and neo-vessel formation. RANTES/CCL5-mediated angiogenesis depends at least partly on Vascular Endothelial Growth Factor (VEGF) secretion by endothelial cells, since this effect is decreased when endothelial cells are incubated with anti-VEGF receptor antibodies. RANTES/CCL5-induced chemotaxis is mediated by matrix metalloproteinase-9. We demonstrate that specific receptors of RANTES/CCL5 such as G protein-coupled receptors CCR1 and CCR5, and heparan sulfate proteoglycans, SDC-1, SDC-4 or CD-44, play a major role in RANTES/CCL5-induced angiogenic effects. By the use of two RANTES/CCL5 mutants, [E66A]-RANTES/CCL5 with impaired ability to oligomerize, and [44AANA47]-RANTES/CCL5 mutated in the main RANTES/CCL5-glycosaminoglycan (GAG) binding site, we demonstrate that chemokine oligomerization and binding to GAGs are essential in RANTES/CCL5-induced angiogenic effects. According to these results, new therapeutic strategies based on RANTES/CCL5 can be proposed for neo-angiogenesis after vascular injury. Mutants of RANTES/CCL5 may also represent an innovative approach to prevent the angiogenesis associated with the formation of atherosclerotic plaque.

Epilepsy surgery for drug-resistant temporal lobe epilepsy in over-50 year-olds: Seizure outcome, surgical complications and neuropsychological outcome.

OBJECTIVE: Surgery is an effective treatment for drug-resistant temporal-lobe epilepsy (TLE), but is still underutilized for older patients because of a perceived higher rate of perioperative complications, cognitive decline and worse seizure outcome. METHODS: We retrospectively screened all patients operated on in our institution for drug-resistant TLE between 2007 and 2019. Data of patients aged ≥50 years versus <50 years at surgery were compared. The primary endpoint was freedom from disabling seizure (Engel I) at 2 years postoperatively. RESULTS: In patients aged ≥50 years (n=19), mean age at surgery was 54.9 years and mean disease duration was 36.6 years. At 2 years postoperatively, rates of Engel I seizure outcome were not significantly different between the two groups (73.9% in the <50 years group versus 94.4% in the ≥50 years group). Although surgical complications were significantly (47.4%) in the older patients, neurological deficit was permanent in only 5.3% of cases. At 1 year postoperatively, neuropsychological outcome did not significantly differ between the two groups. CONCLUSIONS: Patients aged ≥50 years had an excellent seizure outcome at 2 years postoperatively. Early postoperative complications were more frequent in patients aged ≥50 years but were mostly transient. Cognitive outcome was similar to that in younger patients. These findings strongly suggest that age ≥50 years should not be an exclusion criterion for resective epilepsy surgery in patients with drug-resistant TLE.

Drug-resistant temporal lobe epilepsy is associated with postural control abnormalities.

Epilepsy is responsible for falls that are not systematically associated with seizures and that therefore suggest postural impairment. There are very few studies of postural control in patients with epilepsy and none of them focus on temporal lobe epilepsy (TLE), although part of the vestibular cortex is located in the temporal cortex. The aim of this study was to evaluate the characteristics of postural control in a homogeneous population of patients with complex partial TLE. Twenty-six patients with epilepsy and 26 age-matched healthy controls underwent a sensory organization test combining six conditions, with and without sensory conflicting situations. Patients with epilepsy displayed poorer postural control, especially in situations where vestibular information is necessary to control balance. In addition to potential antiepileptic drug side effects, vestibular dysfunction could be related to the temporal pathology. Our study allows for a better understanding of the mechanism underlying falls in this population of patients.

Psychogenic nonepileptic seizures: characterization of two distinct patient profiles on the basis of trauma history.

This prospective study investigated and compared psychiatric features of 25 consecutive patients with psychogenic nonepileptic seizures (PNES) on the basis of presence of reported trauma. The "trauma" group comprised 19 patients (76%) and the "no-trauma" group comprised 6 patients (34%). We compared history of PNES, psychiatric comorbidity, alexithymia, and symptoms of dissociation. The study clearly characterized two distinct profiles of patients with PNES on the basis of trauma history. Patients with trauma had at least one psychiatric comorbidity or antecedent (vs 0% in the no-trauma group NT, P<0.001) and a higher median score of dissociation (P<0.001). Patients without trauma had more frequent "frustration situations" as a factor triggering PNES and subsequent sick leaves as perpetuating factors (P=0.001). Trauma antecedents correlated with a high rate of psychiatric comorbidity and a strong dissociative mechanism. Patients without trauma had no psychiatric comorbidity and a weaker dissociative mechanism.

Automated cortical projection of EEG sensors: anatomical correlation via the international 10-10 system.

Several studies have described cranio-cerebral correlations in accordance with the 10-20 electrode placement system. These studies have made a significant contribution to human brain imaging techniques, such as near-infrared spectroscopy and trans-magnetic stimulation. With the recent development of high resolution EEG, an extension of the 10-20 system has been proposed. This new configuration, namely the 10-10 system, allows the placement of a high number (64-256) of EEG electrodes. Here, we describe the cranio-cerebral correlations with the 10-10 system. Thanks to the development of a new EEG-MRI sensor and an automated algorithm which enables the projection of electrode positions onto the cortical surface, we studied the cortical projections in 16 healthy subjects using the Talairach stereotactic system and estimated the variability of cortical projections in a statistical way. We found that the cortical projections of the 10-10 system could be estimated with a grand standard deviation of 4.6 mm in x, 7.1 mm in y and 7.8 mm in z. We demonstrated that the variability of projections is greatest in the central region and parietal lobe and least in the frontal and temporal lobes. Knowledge of cranio-cerebral correlations with the 10-10 system should enable to increase the precision of surface brain imaging and should help electrophysiological analyses, such as localization of superficial focal cortical generators.

[Risk of epilepsy after a first epileptic seizure in adults: Can we predict the future?]. / Prise en charge d'une première crise épileptique de l'adulte : peut-on prévoir l'avenir ?

The new definition of epilepsy recently proposed by an international panel of experts relies on the association of a first clinically certain seizure and of an enduring predisposition of the brain increasing the likelihood of future seizures. In the first part of this review, we will expose and organize into a hierarchical order the risk factors of subsequent recurrence. The major factors are: seizure(s) prior to presentation, paroxysmal abnormalities on early EEG, a remote symptomatic etiology. In the second part of this review, we will address the issue of clinical uncertainty when assessing the epileptic origin of a first clinical paroxysmal event, the reasons of uncertainty and the means to minimize it. We will analyze successively: the accuracy of eyewitness observations of transient loss of consciousness, the reliability and predictive validity of clinical criteria used for seizure assessment, the issue of overlapping clinical features between seizure and other non epileptic paroxysmal events (such as psychogenic non epileptic seizures), and finally the reliability and diagnostic value of early EEG for seizure assessment. To conclude, seizure assessment and diagnosis of epilepsy cannot be dissociated from syndrome and etiology diagnosis, which should be periodically reassessed towards a greater accuracy during the course of the disease.

Spatial localization of EEG electrodes.

AIM OF THE STUDY: An important goal for EEG-based functional brain studies is to estimate the location of brain sources that produce the scalp-recorded signals. Such source localization requires locating precisely the position of the EEG sensors. This review describes and compares different methods that are used for localizing EEG sensors. RESULTS: Five different methods have been described in literature. Manual methods consist in manual measurements to calculate the 3D coordinates of the sensors. Electromagnetic and ultrasound digitization permit localization by using trade devices. The photogrammetry system consists in taking pictures of the patient's head with the sensors. The last method consists in directly localizing the EEG sensors in the MRI volume. DISCUSSION AND CONCLUSIONS: The spatial localization of EEG sensors is an important step in performing source localization. This method should be accurate, fast, reproducible, and cheap. Currently, electromagnetic digitization is the most currently used method but MRI localization could be an interesting way because no additional method or device needs to be used to locate the EEG sensors.

Automatic lateralization of temporal lobe epilepsy based on scalp EEG.

OBJECTIVE: The objective of this work is the determination of the lateralization of the epileptic seizure onset zone using the scalp EEG signal processing. METHODS: A comprehensive method based on the evaluation of the evolution of the correlation coefficients computed between bipolar channels (longitudinal montage) was applied to 43 patients (87 seizures). The correlation coefficients are estimated by a nonlinear regression analysis. The methodology that leads to the lateralization is based on several processing steps: segmentation, seizure onset determination and then lateralization. RESULTS: Results show that the mean level of the nonlinear correlation values computed between EEG channels at the seizure onset time is significantly higher on the side of the beginning of a seizure. CONCLUSIONS: The side of the seizure onset was determined for about 80-90% of the seizures studied with a satisfactory high reproducibility level. SIGNIFICANCE: Comparison of nonlinear correlation coefficients between both sides of the brain leads to the determination of the side of seizure onset.

[MRI findings in a case of prolonged status epilepticus]. / Suivi iconographique d'un etat de mal epileptique prolonge.

We report the MR imaging findings in a 20 year old woman with status epilepticus of more than 3 months duration following an episode of lymphocytic meningitis. Repeated MR examinations showed progressive symmetrical cortical lesions, followed by subcortical and basal ganglia lesions which evolved to cortical laminar necrosis and hemorrhagic necrosis with eventual subcortical cerebral atrophy. This case has similarities with animal status epilepticus models. Biological investigations were all negative. This suggests that the brain lesions may be related to the prolonged status epilepticus.

Stent placement compared with balloon angioplasty for small coronary arteries: in-hospital and 6-month clinical and angiographic results.

BACKGROUND: Stenting has been demonstrated to be superior to balloon angioplasty in de novo focal lesions located in large native vessels. However, in small vessels, the benefit of stenting remains questionable. METHODS AND RESULTS: A total of 381 symptomatic patients with de novo focal lesion located on a small coronary segment vessel (<3 mm) were randomly assigned to either stent implantation (192 patients; 197 lesions) or standard balloon angioplasty (189 patients; 198 lesions). The primary end point was the angiographic restenosis rate at 6 months, as determined by quantitative coronary angiography. On intention-to-treat analysis, angiographic success rate and major adverse cardiac events were comparable: 97.9% and 4.6% versus 93.9% and 5.8% in the stent group and the balloon group, respectively. After the procedure, a larger acute gain was achieved with stent placement (1.35+/-0.45 versus 0.94+/-0.47 mm, P=0.0001), resulting in a larger minimal lumen diameter (2.06+/-0.42 versus 1.70+/-0.46 mm, P=0.0001). At follow-up (obtained in 91% of patients), angiographic restenosis rate was 21% in the stent group versus 47% in the balloon group (P=0.0001), a risk reduction of 55%. Repeat target lesion revascularization was less frequent in the stent group (13% versus 25%, P=0.0006). CONCLUSIONS: Elective stent placement in small coronary arteries with focal de novo lesions is safe and associated with a marked reduction in restenosis rate and subsequent target lesion revascularization rate at 6 months.

Passivation of metallic stents after arterial gene transfer of phVEGF165 inhibits thrombus formation and intimal thickening.

OBJECTIVES: This study sought to test the hypothesis that direct gene transfer of an endothelial cell mitogen could passivate metallic stents by accelerating endothelialization of the prosthesis. BACKGROUND: Thrombosis and restenosis comprise the principal clinical manifestations of compromised biocompatibility of endovascular stents. Previous studies have demonstrated that endothelial recovery at sites of balloon injury is a critical determinant of consequent intimal thickening and mural thrombus. We therefore investigated the potential for an endothelial cell mitogen delivered as plasmid DNA to optimize stent biocompatibility. METHODS: Naked plasmid DNA encoding vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF) (phVEGF165) was delivered locally using a hydrogel-coated balloon angioplasty catheter to 16 rabbit iliac arteries in which metallic stents had been placed at the site of balloon injury; the contralateral iliac artery of each rabbit was balloon injured and stented but not transfected. RESULTS: Stent endothelialization was accelerated by phVEGF165 gene transfer (87.38 +/- 5.06% vs. 33.13 +/- 9.73% [mean +/- SEM] of the planimetered stent surface in the treated vs. contralateral limb, p = 0.005). This was associated with a significant reduction in mural thrombus (3.7 +/- 2.4% vs. 32.7 +/- 9.7%, p = 0.01) at day 7 and intimal thickening (maximal intimal area 0.61 +/- 0.09 vs. 1.44 +/- 0.12 mm2, p < 0.0001) at day 28. No benefit was observed from pCMV-luciferase in 14 similarly instrumented control rabbits. CONCLUSIONS: These findings indicate that arterial gene transfer of naked plasmid DNA encoding for an endothelial cell mitogen may successfully passivate endovascular stents by accelerating stent endothelialization, thereby reducing in-stent thrombus and obstruction due to intimal thickening.