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

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

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

Resective, Ablative and Radiosurgical Interventions for Drug Resistant Mesial Temporal Lobe Epilepsy: A Systematic Review and Meta-Analysis of Outcomes

Objectives: One-third of individuals with focal epilepsy do not achieve seizure freedom despite best medical therapy. Mesial temporal lobe epilepsy (MTLE) is the most common form of drug resistant focal epilepsy. Surgery may lead to long-term seizure remission if the epileptogenic zone can be defined and safely removed or disconnected. We compare published outcomes following open surgical techniques, radiosurgery (SRS), laser interstitial thermal therapy (LITT) and radiofrequency ablation (RF-TC). / Methods: PRISMA systematic review was performed through structured searches of PubMed, Embase and Cochrane databases. Inclusion criteria encompassed studies of MTLE reporting seizure-free outcomes in ≥10 patients with ≥12 months follow-up. Due to variability in open surgical approaches, only comparative studies were included to minimize the risk of bias. Random effects meta-analysis was performed to calculate effects sizes and a pooled estimate of the probability of seizure freedom per person-year. A mixed effects linear regression model was performed to compare effect sizes between interventions. / Results: From 1,801 screened articles, 41 articles were included in the quantitative analysis. Open surgery included anterior temporal lobe resection as well as transcortical and trans-sylvian selective amygdalohippocampectomy. The pooled seizure-free rate per person-year was 0.72 (95% CI 0.66–0.79) with trans-sylvian selective amygdalohippocampectomy, 0.59 (95% CI 0.53–0.65) with LITT, 0.70 (95% CI 0.64–0.77) with anterior temporal lobe resection, 0.60 (95% CI 0.49–0.73) with transcortical selective amygdalohippocampectomy, 0.38 (95% CI 0.14–1.00) with RF-TC and 0.50 (95% CI 0.34–0.73) with SRS. Follow up duration and study sizes were limited with LITT and RF-TC. A mixed-effects linear regression model suggests significant differences between interventions, with LITT, ATLR and SAH demonstrating the largest effects estimates and RF-TC the lowest. / Conclusions: Overall, novel “minimally invasive” approaches are still comparatively less efficacious than open surgery. LITT shows promising seizure effectiveness, however follow-up durations are shorter for minimally invasive approaches so the durability of the outcomes cannot yet be assessed. Secondary outcome measures such as Neurological complications, neuropsychological outcome and interventional morbidity are poorly reported but are important considerations when deciding on first-line treatments

Automated trajectory planning for laser interstitial thermal therapy in mesial temporal lobe epilepsy

OBJECTIVE: Surgical resection of the mesial temporal structures brings seizure remission in 65% of individuals with drug-resistant mesial temporal lobe epilepsy (MTLE). Laser interstitial thermal therapy (LiTT) is a novel therapy that may provide a minimally invasive means of ablating the mesial temporal structures with similar outcomes, while minimizing damage to the neocortex. Systematic trajectory planning helps ensure safety and optimal seizure freedom through adequate ablation of the amygdalohippocampal complex (AHC). Previous studies have highlighted the relationship between the residual unablated mesial hippocampal head and failure to achieve seizure freedom. We aim to implement computer-assisted planning (CAP) to improve the ablation volume and safety of LiTT trajectories. METHODS: Twenty-five patients who had previously undergone LiTT for MTLE were studied retrospectively. The EpiNav platform was used to automatically generate an optimal ablation trajectory, which was compared with the previous manually planned and implemented trajectory. Expected ablation volumes and safety profiles of each trajectory were modeled. The implemented laser trajectory and achieved ablation of mesial temporal lobe structures were quantified and correlated with seizure outcome. RESULTS: CAP automatically generated feasible trajectories with reduced overall risk metrics (P < .001) and intracerebral length (P = .007). There was a significant correlation between the actual and retrospective CAP-anticipated ablation volumes, supporting a 15 mm diameter ablation zone model (P < .001). CAP trajectories would have provided significantly greater ablation of the amygdala (P = .0004) and AHC (P = .008), resulting in less residual unablated mesial hippocampal head (P = .001), and reduced ablation of the parahippocampal gyrus (P = .02). SIGNIFICANCE: Compared to manually planned trajectories CAP provides a better safety profile, with potentially improved seizure-free outcome and reduced neuropsychological deficits, following LiTT for MTLE

Minimal Flavour Violation with hierarchical squark masses

In a supersymmetric model with hierarchical squark masses we analyze a pattern of flavour symmetry breaking centered on the special role of the top Yukawa coupling and, by extension, of the full Yukawa couplings for the up-type quarks. For sufficiently heavy squarks of the first and second generation this leads to effective Minimal Flavour Violation of the Flavour Changing Neutral Current amplitudes. For this to happen we determine the bounds on the masses of the heavy squarks with QCD corrections taken into account, properly including previously neglected effects. We believe that the view presented in this paper altogether strengthens the case for hierarchical sfermions.Comment: 13 pages, 1 figure. v2: an equation correcte

Improving patient safety during introduction of novel medical devices through cumulative summation analysis

Objective: To implement cumulative summation analysis (CUSUM) as an early warning detection and quality assurance system for the pre-clinical testing of the iSYS1 novel robotic trajectory guidance system. Methods: Anatomically accurate 3D printed skull phantoms were created for three patients that had previously undergone implantation of 21 stereoelectroencephalography (SEEG) electrodes using the current standard of care (frameless technique). Implantation schema were recreated using the iSYS1 system and paired accuracy measures were compared with the previous frameless implantations. Entry point, target point and implantation angle accuracy were measured from post-implantation CT scans. CUSUM analysis was undertaken prospectively. Results: The iSYS1 trajectory guidance system significantly improved electrode entry point accuracies from 1.90+/-0.96 mm (Mean+/-SD) to 0.76+/-0.57 mm (Mean+/-SD) without increasing implantation risk. CUSUM analysis was successful as a continuous measure of surgical performance and acted as an early warning detection system. The surgical learning curve, although minimal, showed improvement after insertion of the 8th electrode. Conclusions: The iSYS1 trajectory guidance system did not show any increased risk during phantom preclinical testing when performed by neurosurgeons who had no previous experience of its use. CUSUM analysis is a simple technique that can be applied to all stages of the IDEAL framework as an extra patient safety mechanism. Further clinical trials are required to prove the efficacy of the device

Quantitative principles of cis-translational control by general mRNA sequence features in eukaryotes.

BackgroundGeneral translational cis-elements are present in the mRNAs of all genes and affect the recruitment, assembly, and progress of preinitiation complexes and the ribosome under many physiological states. These elements include mRNA folding, upstream open reading frames, specific nucleotides flanking the initiating AUG codon, protein coding sequence length, and codon usage. The quantitative contributions of these sequence features and how and why they coordinate to control translation rates are not well understood.ResultsHere, we show that these sequence features specify 42-81% of the variance in translation rates in Saccharomyces cerevisiae, Schizosaccharomyces pombe, Arabidopsis thaliana, Mus musculus, and Homo sapiens. We establish that control by RNA secondary structure is chiefly mediated by highly folded 25-60 nucleotide segments within mRNA 5' regions, that changes in tri-nucleotide frequencies between highly and poorly translated 5' regions are correlated between all species, and that control by distinct biochemical processes is extensively correlated as is regulation by a single process acting in different parts of the same mRNA.ConclusionsOur work shows that general features control a much larger fraction of the variance in translation rates than previously realized. We provide a more detailed and accurate understanding of the aspects of RNA structure that directs translation in diverse eukaryotes. In addition, we note that the strongly correlated regulation between and within cis-control features will cause more even densities of translational complexes along each mRNA and therefore more efficient use of the translation machinery by the cell

Exact Tunneling Solutions in Minkowski Spacetime and a Candidate for Dark Energy

We study exact tunneling solutions in scalar field theory for potential barriers composed of linear or quadratic patches. We analytically continue our solutions to imaginary Euclidean radius in order to study the profile of the scalar field inside the growing bubble. We find that generally there is a non-trivial profile of the scalar field, generating a stress-energy tensor, that depending on the form of the potential, can be a candidate for dark energy.Comment: 39 pages, 12 figure