Auras and the risk of seizures with impaired consciousness following epilepsy surgery: implications for driving

OBJECTIVE: To calculate the chance of a seizure in the next year (COSY) for seizures with impaired awareness in those experiencing auras only, those with no seizures and those with continuing seizures. Epilepsy surgery is an effective treatment for refractory focal epilepsy. Driving is an important factor affecting quality of life. In the UK, driving is not permitted if focal seizures with no impairment of awareness (auras, simple partial seizures) continue, if there is a prior history of seizures with impaired awareness, as will invariably be the case in those having epilepsy surgery. Current UK driving regulations allow driving if COSY is less than 20%. METHOD: We calculated COSY in 819 epilepsy surgery patients with up to 25 years follow-up. Each patient year was graded on the The International League against Epilepsy surgery outcome scale. RESULTS: Patients who were entirely seizure-free for 1, 2 and 3 years had COSY of 4.9%, 3.5% and 2.4% respectively. Patients with only auras within the last 1, 2 or 3 years had a COSY of 11.3%, 9.2% and 7.8% respectively. CONCLUSIONS: Individuals with auras only after epilepsy surgery had a higher COSY than those who were seizure-free. If a COSY of below 20% is regarded as an acceptable risk, it may be suggested that those with auras only in a given year be allowed to drive. The relative risk of these patients causing accidents is lower than population groups such as those aged 75 years, who are permitted to drive

Geant4 Monte Carlo simulation study of the secondary radiation fields at the laser-driven ion source LION

At the Center for Advanced Laser Applications (CALA), Garching, Germany, the LION (Laser-driven ION Acceleration) experiment is being commissioned, aiming at the production of laser-driven bunches of protons and light ions with multi-MeV energies and repetition frequency up to 1 Hz. A Geant4 Monte Carlo-based study of the secondary neutron and photon fields expected during LION’s different commissioning phases is presented. Goal of this study is the characterization of the secondary radiation environment present inside and outside the LION cave. Three different primary proton spectra, taken from experimental results reported in the literature and representative of three different future stages of the LION’s commissioning path are used. Together with protons, also electrons are emitted through laser-target interaction and are also responsible for the production of secondary radiation. For the electron component of the three source terms, a simplified exponential model is used. Moreover, in order to reduce the simulation complexity, a two-components simplified geometrical model of proton and electron sources is proposed. It has been found that the radiation environment inside the experimental cave is either dominated by photons or neutrons depending on the position in the room and the source term used. The higher the intensity of the source, the higher the neutron contribution to the total dose for all scored positions. Maximum neutron and photon ambient dose equivalent values normalized to 10(9) simulated incident primaries were calculated at the exit of the vacuum chamber, where values of about 85 nSv (10(9) primaries)(−1) and 1.0 μSv (10(9) primaries)(−1) were found

Premature mortality in refractory partial epilepsy: does surgical treatment make a difference?

Background: Epilepsy carries an increased risk of premature death. For some people with intractable focal epilepsy, surgery offers hope for a seizure-free life. The authors aimed to see whether epilepsy surgery influenced mortality in people with intractable epilepsy. Methods: The authors audited survival status in two cohorts (those who had surgery and those who had presurgical assessment but did not have surgery). Results: There were 40 known deaths in the non-surgical group (3365 person years of follow-up) and 19 in the surgical group (3905 person-years of follow-up). Non-operated patients were 2.4 times (95% CI 1.4 to 4.2) as likely to die as those who had surgery. They were 4.5 times (95% CI 1.9 to 10.9) as likely to die a probable epilepsy-related death. In the surgical group, those with ongoing seizures 1 year after surgery were 4.0 (95% CI 1.2 to 13.7) times as likely to die as those who were seizure-free or who had only simple partial seizures. Time-dependent Cox analysis showed that the yearly outcome group did not significantly affect mortality (HR 1.3, 95% CI 0.9 to 1.8). Conclusion: Successful epilepsy surgery was associated with a reduced risk of premature mortality, compared with those with refractory focal epilepsy who did not have surgical treatment. To some extent, the reduced mortality is likely to be conferred by inducing freedom from seizures. It is not certain whether better survival is attributable only to surgery, as treatment decisions were not randomised, and there may be inherent differences between the groups.<br/

MRI in the diagnosis and management of epileptomas.

High-resolution magnetic resonance imaging (MRI) is invaluable for identifying cerebral tumors that cause epilepsy. Serial voxel-based automated quantitative analyses are more sensitive than visual reading for detecting change in a lesion. Eloquent cortex can be identified with functional MRI (fMRI), with cautions about the precise location and extent of critical cortex. Tractography is useful for delineating critical white matter tracks as are MR venography and computerized tomography (CT) angiography for displaying veins and arteries. These data may be combined into a three-dimensional (3D) multimodal MR data presentation and displayed interoperatively to increase the precision and minimize the risk of neurosurgical treatment, and for the illustrations

Formally Defining and Iterating Infinite Models

International audienceThe wide adoption of MDE raises new situations where we need to manipulate very large models or even infinite model streams gathered at runtime. These new uses cases for MDE raise challenges that had been unforeseen by the time standard modeling framework were designed. This paper proposes a formal definition of an infinite model, as well as a formal framework to reason on queries over infinite models. This formal query definition aims at supporting the design and verification of operations that manipulate infinite models. First, we precisely identify the MOF parts which must be refined to support infinite structure. Then, we provide a formal coinductive definition dealing with unbounded and potentially infinite graph-based structure

Seizure outcomes in people with drug-resistant focal epilepsy evaluated for surgery but do not proceed

Objective: To ascertain seizure outcomes in people with drug-resistant focal epilepsy considered for epilepsy surgery but who did not proceed. // Methods: We identified people discussed at a weekly presurgical epilepsy multi-disciplinary (MDT) meeting from January 2015 to December 2019 and in whom a decision not to proceed to surgery was made. Seizure outcomes were obtained from individuals, primary care physicians and attending neurologists at a minimum of 12 months following the not to proceed decision. // Results: We considered 315 people who did not proceed to surgery after evaluation. Nine died, and 25 were lost to follow-up. We included 281 people with a median follow-up of 2.4 (IQR 1.5–4) years. In total, 83 (30%) people reported that seizures had improved or resolved since the MDT meeting. Thirteen (5%) were seizure-free over the last 12 months of follow-up, 70 (25%) had experienced more than 50% reduction in seizure frequency, 180 (64%) had no meaningful change, and 18 (6%) reported a doubling of seizure frequency. Of the 53 (16%) who had vagal nerve stimulation, 19/53 (37%) reported more than 50% reduction in frequency, including one seizure-free. // Significance: The chances of seizure freedom with further medications and neurostimulation are low for people with drug-resistant focal epilepsy who have been evaluated for surgery and do not proceed, but improvement may still occur. Up to a quarter have a > 50% reduction in seizures, and one in twenty become seizure-free eventually. Trying additional anti-seizure medication and neurostimulation is worthwhile in this population

Voxel-based magnetic resonance image postprocessing in epilepsy

OBJECTIVE: Although the general utility of voxel-based processing of structural magnetic resonance imaging (MRI) data for detecting occult lesions in focal epilepsy is established, many differences exist among studies, and it is unclear which processing method is preferable. The aim of this study was to compare the ability of commonly used methods to detect epileptogenic lesions in magnetic resonance MRI-positive and MRI-negative patients, and to estimate their diagnostic yield. METHODS: We identified 144 presurgical focal epilepsy patients, 15 of whom had a histopathologically proven and MRI-visible focal cortical dysplasia; 129 patients were MRI negative with a clinical hypothesis of seizure origin, 27 of whom had resections. We applied four types of voxel-based morphometry (VBM), three based on T1 images (gray matter volume, gray matter concentration, junction map [JM]) and one based on normalized fluid-attenuated inversion recovery (nFSI). Specificity was derived from analysis of 50 healthy controls. RESULTS: The four maps had different sensitivity and specificity profiles. All maps showed detection rates for focal cortical dysplasia patients (MRI positive and negative) of >30% at a strict threshold of p 60% with a liberal threshold of p < 0.0001 (uncorrected), except for gray matter volume (14% and 27% detection rate). All maps except nFSI showed poor specificity, with high rates of false-positive findings in controls. In the MRI-negative patients, absolute detection rates were lower. A concordant nFSI finding had a significant positive odds ratio of 7.33 for a favorable postsurgical outcome in the MRI-negative group. Spatial colocalization of JM and nFSI was rare, yet showed good specificity throughout the thresholds. SIGNIFICANCE: All VBM variants had specific diagnostic properties that need to be considered for an adequate interpretation of the results. Overall, structural postprocessing can be a useful tool in presurgical diagnostics, but the low specificity of some maps has to be taken into consideration

Reasons for not having epilepsy surgery

Objective: This study was undertaken to determine reasons for adults with drug-resistant focal epilepsy who undergo presurgical evaluation not proceeding with surgery, and to identify predictors of this course. // Methods: We retrospectively analyzed data on 617 consecutive individuals evaluated for epilepsy surgery at a tertiary referral center between January 2015 and December 2019. We compared the characteristics of those in whom a decision not to proceed with surgical treatment was made with those who underwent definitive surgery in the same period. Multivariate logistic regression was performed to identify predictors of not proceeding with surgery. // Results: A decision not to proceed with surgery was reached in 315 (51%) of 617 individuals evaluated. Common reasons for this were an inability to localize the epileptogenic zone (n = 104) and the presence of multifocal epilepsy (n = 74). An individual choice not to proceed with intracranial electroencephalography (icEEG; n = 50) or surgery (n = 39), risk of significant deficit (n = 33), declining noninvasive investigation (n = 12), and coexisting neurological comorbidity (n = 3) accounted for the remainder. Compared to 166 surgically treated patients, those who did not proceed to surgery were more likely to have a learning disability (odds ratio [OR] = 2.35, 95% confidence interval [CI] = 1.07‒5.16), normal magnetic resonance imaging (OR = 4.48, 95% CI = 1.68–11.94), extratemporal epilepsy (OR = 2.93, 95% CI = 1.82‒4.71), bilateral seizure onset zones (OR = 3.05, 95% CI = 1.41‒6.61) and to live in more deprived socioeconomic areas (median deprivation decile = 40%–50% vs. 50%–60%, p < .05). // Significance: Approximately half of those evaluated for surgical treatment of drug-resistant focal epilepsy do not proceed to surgery. Early consideration and discussion of the likelihood of surgical suitability or need for icEEG may help direct referral for presurgical evaluation

Status epilepticus and thinning of the entorhinal cortex

Status epilepticus (SE) carries risks of morbidity and mortality. Experimental studies have implicated the entorhinal cortex in prolonged seizures; however, studies in large human cohorts are limited. We hypothesised that individuals with temporal lobe epilepsy (TLE) and a history of SE would have more severe entorhinal atrophy compared to others with TLE and no history of SE. 357 individuals with drug resistant temporal lobe epilepsy (TLE) and 100 healthy controls were scanned on a 3T MRI. For all subjects, the cortex was segmented, parcellated, and the thickness calculated from the T1-weighted anatomical scan. Subcortical volumes were derived similarly. Cohen's d and Wilcoxon rank-sum tests respectively were used to capture effect sizes and significance. Individuals with TLE and SE had reduced entorhinal thickness compared to those with TLE and no history of SE. The entorhinal cortex was more atrophic ipsilaterally (d = 0.51, p < 0.001) than contralaterally (d = 0.37, p = 0.01). Reductions in ipsilateral entorhinal thickness were present in both left TLE (n = 22:176, d = 0.78, p < 0.001), and right TLE (n = 19:140, d = 0.31, p = 0.04), albeit with a smaller effect size in right TLE. Several other regions exhibited atrophy in individuals with TLE, but these did not relate to a history of SE. These findings suggest potential involvement or susceptibility of the entorhinal cortex in prolonged seizures

High-throughput, automated quantification of white matter neurons in mild malformation of cortical development in epilepsy

Introduction In epilepsy, the diagnosis of mild Malformation of Cortical Development type II (mMCD II) predominantly relies on the histopathological assessment of heterotopic neurons in the white matter. The exact diagnostic criteria for mMCD II are still ill-defined, mainly because findings from previous studies were contradictory due to small sample size, and the use of different stains and quantitative systems. Advance in technology leading to the development of whole slide imaging with high-throughput, automated quantitative analysis (WSA) may overcome these differences, and may provide objective, rapid, and reliable quantitation of white matter neurons in epilepsy. This study quantified the density of NeuN immunopositive neurons in the white matter of up to 142 epilepsy and control cases using WSA. Quantitative data from WSA was compared to two other systems, semi-automated quantitation, and the widely accepted method of stereology, to assess the reliability and quality of results from WSA. Results All quantitative systems showed a higher density of white matter neurons in epilepsy cases compared to controls (P = 0.002). We found that, in particular, WSA with user-defined region of interest (manual) was superior in terms of larger sampled size, ease of use, time consumption, and accuracy in region selection and cell recognition compared to other methods. Using results from WSA manual, we proposed a threshold value for the classification of mMCD II, where 78% of patients now classified with mMCD II were seizure-free at the second post-operatively follow up. Conclusion This study confirms the potential role of WSA in future quantitative diagnostic histology, especially for the histopathological diagnosis of mMCD