Rapid eye movement sleep and epilepsy: exploring interactions and therapeutic prospects.

While research interest in the relationship between sleep and epilepsy is growing, it primarily centres on the effects of non-rapid eye movement (NREM) sleep in favouring seizures. Nonetheless, a noteworthy aspect is the observation that, in the lives of patients with epilepsy, REM sleep represents the moment with the least epileptic activity and the lowest probability of having a seizure. Studies demonstrate a suppressive effect of phasic REM sleep on interictal epileptiform discharges, potentially offering insights into epilepsy localisation and management. Furthermore, epilepsy impacts REM sleep, with successful treatment correlating with improved REM sleep quality. Novel therapeutic strategies aim to harness REM's anti-epileptic effects, including pharmacological approaches targeting orexinergic systems and neuromodulation techniques promoting cortical desynchronisation. These findings underscore the intricate relationship between REM sleep and epilepsy, highlighting avenues for further research and therapeutic innovation in epilepsy management.

The challenges of treating status epilepticus in rural Canada.

Though unified by challenges in the treatment of status epilepticus (SE), rural Canada is simultaneously massive and diverse, spanning the Pacific, Atlantic, and Arctic Oceans. According to the national statistical agency, the most rural jurisdiction in Canada is the Arctic territory of Nunavut. In particular, the Kivalliq region of Nunavut represents a unique epidemiologic SE space because any treatment beyond typical first-line lorazepam and second-line phenytoin by a non-neurologist locum tenens requires airborne evacuation over a thousand kilometers away to a single hospital with a single electroencephalographic (EEG) laboratory. This distinctive mode of healthcare delivery affords unique insights into the challenges of treating SE in rural Canada, such as lack of EEG infrastructure, a markedly high incidence of SE, the struggles of enduring cultural and socioeconomic trauma, and a relative lack of local epilepsy care as recommended by the World Health Organization. For example, despite empiric treatment and waiting over 2 days on average for EEG, 1 in 5 patients still had ongoing or possible electrographic seizures. At the same time, Kivalliq experiences routine dramatic changes in light-dark exposure each year to afford unique insights into circannual SE chronobiology in relation to the chief human zeitgeber of sunlight. This shows that challenges may also represent opportunities, such as for existing and emerging technologies to synergistically address enormous treatment gaps to improve SE care for the people of Kivalliq, while providing novel insights that may also help improve SE clinical care around the world.

Residual Seizure Rate of Intermittent Inpatient EEG Compared to a Continuous EEG Model.

BACKGROUND: Subclinical seizures are common in hospitalized patients and require electroencephalography (EEG) for detection and intervention. At our institution, continuous EEG (cEEG) is not available, but intermittent EEGs are subject to constant live interpretation. As part of quality improvement (QI), we sought to estimate the residual missed seizure rate at a typical quaternary Canadian health care center without cEEG. METHODS: We calculated residual risk percentages using the clinically validated 2HELPS2B score to risk-stratify EEGs before deriving a risk percentage using a MATLAB calculator which modeled the risk decay curve for each recording. We generated a range of estimated residual seizure rates depending on whether a pre-cEEG screening EEG was simulated, EEGs showing seizures were included, or repeat EEGs on the same patient were excluded. RESULTS: Over a 4-month QI period, 499 inpatient EEGs were scored as low (n = 125), medium (n = 123), and high (n = 251) seizure risk according to 2HELPS2B criteria. Median recording duration was 1:00:06 (interquartile range, IQR 30:40-2:21:10). The model with highest residual seizure rate included recordings with confirmed electrographic seizures (median 20.83%, IQR 20.6-26.6%), while the model with lowest residual seizure rate was in seizure-free recordings (median 10.59%, IQR 4%-20.6%). These rates were significantly higher than the benchmark 5% miss-rate threshold set by 2HELPS2B (p<0.0001). CONCLUSIONS: We estimate that intermittent inpatient EEG misses 2-4 times more subclinical seizures than the 2HELPS2B-determined acceptable 5% seizure miss-rate threshold for cEEG. Future research is needed to determine the impact of potentially missed seizures on clinical care.

Antiseizure medication use during pregnancy and neonatal growth outcomes: A systematic review and meta-analysis.

AIMS: We aimed to systematically synthesize the current published literature on neonatal growth outcomes associated with antiseizure medication (ASM) use during pregnancy. METHODS: We searched seven databases, from inception to 23 March 2022. We investigated small for gestational age (SGA) and low birth weight (LBW) as primary outcomes and birth weight, birth height, cephalization index and head circumference as secondary outcomes. The primary analysis included pregnant people exposed to any ASM compared with unexposed pregnant people. Subgroup analysis included ASM class analysis, within epilepsy group analysis and polytherapy compared to monotherapy. RESULTS: We screened 15 720 citations and included 65 studies in the review. Exposed pregnant people had a significantly increased risk of SGA relative risk (RR) 1.33 (95% CI 1.18 to 1.50, I2 74%), LBW RR 1.54 (95% CI 1.33 to 1.77, I2 67%), and decreased birth weight with a mean difference (MD) of -118.87 (95% CI -161.03 to -76.71, I2 42%) g. A non-significant risk change in birth height and head circumference was observed. In subgroup analysis, ASM polytherapy, within epilepsy and ASM class analysis were also associated with an increased risk of SGA and LBW. CONCLUSIONS: This meta-analysis demonstrates that pregnant people exposed to ASMs have a significantly increased risk of adverse fetal growth outcomes including SGA and LBW and decreased birth weight compared to unexposed pregnant people. Polytherapy was associated with higher risks compared to monotherapy. Additional studies are warranted on specific ASM risks.

Circannual incidence of seizure evacuations from the Canadian Arctic.

OBJECTIVES: Emerging evidence suggests that circadian rhythms affect seizure propensity in addition to, and possibly independent of, sleep-wake states. Subject to extreme seasonal changes in light and dark, the northerly Arctic can serve as a "natural experiment" to assess the real-life impact of environmental influences on seizure severity. Therefore, we evaluated the timing of seizure evacuations over 11.25 years in a well-defined region of the Canadian Arctic. METHODS: Retrospective review of EEG database and patient records at the single "bottleneck" hospital to which all patients from the Kivalliq Region in Nunavut, Canada are evacuated for seizure emergencies. We calculated the mean resultant length (MRL) of circular data for circannual analysis, and conducted Rayleigh's test to assess for a statistical departure from circular uniformity. RESULTS: Screening 40,392 EEGs, we found 117 medical evacuations from 99 distinct individuals from September 2009 to November 2020. Most evacuations occurred month-wise in May (19%); week-wise within a 7-day period in February (5%), June (5%), or November (5%); and day-wise within a 24-hour period in June (3%) or November (3%). Maximal MRL clustering occurred in April no matter if analyzed by day (0.16333, p = 0.04), week (0.16296, p = 0.04), or month (0.1736, p = 0.03). CONCLUSIONS: A relative circannual increase in seizure evacuations between the winter and summer solstices may be related to increasing sleep loss when day length grows. Fewer evacuations between the summer and winter solstices may be related to decreased daylight and "catching up" on sleep when night length grows. Additional factors likely also play a role in circannual variation of seizure evacuations in the Arctic, which warrants further research.

Canadian epilepsy priority-setting partnership: Toward a new national research agenda.

BACKGROUND: Health research agendas are often set by researchers or by industry and may not reflect the needs and priorities of end users. This priority-setting partnership (PSP) for epilepsy was undertaken to identify the most pressing unanswered questions about epilepsy and seizures from the perspective of people with epilepsy (PWE) and their care providers. METHODS: Using the methodology developed by the James Lind Alliance (JLA), evidence uncertainties were gathered via online surveys from stakeholders across Canada. Submissions were formed into summary questions and checked against existing evidence to determine if they were true uncertainties. Verified uncertainties were then ranked by patients, caregivers, and healthcare providers and a final workshop was held to reach a consensus on the top 10 priorities. RESULTS: The final top 10 list reflects the priority areas of focus for research as identified by the Canadian epilepsy community, including genetic markers for diagnosis and treatment, concerns about living with the long-term effects of epilepsy, and addressing knowledge gaps in etiology and treatment approaches. CONCLUSION: This project represents the first systematic evidence of patient- and clinician-centered research priorities for epilepsy. The results of this priority-setting exercise provide an opportunity for researchers and funding agencies to align their agendas with the values and needs of the epilepsy community in order to improve clinical outcomes and quality of life (QOL) for PWE.

Facile and Reproducible Electrochemical Synthesis of the Giant Polyoxomolybdates.

Giant polyoxomolybdates are traditionally synthesized by chemical reduction of molybdate in aqueous solutions, generating complex nanostructures such as the highly symmetrical spherical {Mo102} and {Mo132}, ring-shaped {Mo154} and {Mo176}, and the gigantic protein sized {Mo368}, which combines both positive and negative curvature. These complex polyoxometalates are known to be highly sensitive to reaction conditions and are often difficult to reproduce, especially {Mo368}, which is often produced in yields far below 1%, meaning further investigation has always been limited. While the electrochemical properties of these materials have been studied, their electrochemical synthesis has not been explored. Herein, we demonstrate an alternative reliable synthetic method by means of electrochemistry. By using electrochemical synthesis, we have shown the synthesis of various reported polyoxomolybdates, along with some unreported structures with unique features that have yet to be reported by traditional synthetic methods. The six different giant polyoxomolybdates that were obtained via electrochemical synthesis range from the spherical {Mo102-xFex} and {Mo132} to the ring-shaped {Mo148} and {Mo154-x}, as well as the largest known polyoxometalate {Mo368}, with improved yield (up to 26.1% for {Mo368}), increased reproducibility, and shorter crystallization time compared to chemical reduction methods.

Practice Guidelines for Canadian Neurophysiology Laboratories During the COVID-19 Pandemic.

The COVID-19 pandemic has had a major impact on clinical practice. Safe standards of practice are essential to protect health care workers while still allowing them to provide good care. The Canadian Society of Clinical Neurophysiologists, the Canadian Association of Electroneurophysiology Technologists, the Association of Electromyography Technologists of Canada, the Board of Registration of Electromyography Technologists of Canada, and the Canadian Board of Registration of Electroencephalograph Technologists have combined to review current published literature about safe practices for neurophysiology laboratories. Herein, we present the results of our review and provide our expert opinion regarding the safe practice of neurophysiology during the COVID-19 pandemic in Canada.

A Head-to-Head Comparison of the Medial Sural Artery Perforator versus Radial Forearm Flap for Tongue Reconstruction.

BACKGROUND: For tongue reconstruction, the radial forearm flap (RFF) is commonly used. In the last decade, the medial sural artery perforator (MSAP) flap has been successfully used with reportedly superior donor-site outcomes. Our study is the first to compare the RFF and MSAP for reconstruction of partial glossectomy defects (<50% of tongue). METHODS: We conducted a retrospective review of 20 patients with partial glossectomy defects reconstructed at a tertiary referral center. Patient demographics, perioperative data, and postoperative complications were analyzed. Objective measures of speech, swallowing, and subjective patient satisfaction with their donor site were recorded. RESULTS: Ten RFF and MSAP were each used, with a mean partial glossectomy defect size of 40.5 and 43.5%, respectively. The MSAP was significantly thicker (7.8 vs. 4.3 mm, p < 0.05) with a longer harvest time (122.5 vs. 75.0 minutes, p < 0.05). There were no cases of free flap failure. Donor-site healing times were comparable, but the MSAP group experienced significantly less donor-site complications (n = 1 vs. n = 7, p < 0.05). Functional outcomes were comparable with 13 patients achieving normal speech and diet after 3 months (MSAP = 6 vs. RFF = 7, p = 1.00). All patients were satisfied with their donor-site outcome with the MSAP group having a marginally higher score. CONCLUSION: Both flaps are good options for partial glossectomy reconstruction. Though more challenging to harvest, the MSAP gives comparable functional results and has become our first reconstructive option given its superior donor-site outcomes.

Continuous Infusion Versus Intermittent Boluses of Furosemide in Acute Heart Failure: A Systematic Review and Meta-Analysis.

BACKGROUND: Acute heart failure is a common cause of hospital admission. This study aims to compare continuous infusion and intermittent boluses of furosemide in treating acute heart failure. METHODS: Electronic searches were performed on PubMed, Medline, Scopus, and EMBASE. English articles comparing intermittent boluses and continuous infusion of furosemide in treating acute heart failure were included. Non-comparative studies or articles, and articles that did not report specific data for acute heart failure patients were excluded. Primary endpoints included post-treatment daily urine output, weight, length of stay, and serum sodium, potassium, and creatinine. Secondary endpoints included other pre-treatment and treatment variables. Post hoc trial sequential analysis (TSA) was performed on selected variables. RESULTS: Ten randomized controlled trials were included with a total of 735 patients (371 with intermittent boluses and 364 with continuous infusion). Mean daily urine output (P < .001) and weight loss (P = .04) were significantly higher in the continuous infusion group. Other variables were not significantly different between the two groups. TSA showed that current evidence is sufficient to draw the above conclusions about mean daily urine output, but more studies were required to compare the 2 regimens in terms of weight loss. CONCLUSION: Choice of furosemide regime in acute heart failure remains physician preference. Both bolus and continuous infusion yields satisfactory outcomes.

General Anesthesia Versus Local Anesthesia in Carotid Endarterectomy: A Systematic Review and Meta-Analysis.

OBJECTIVE: The choice of anesthetic technique in carotid endarterectomy (CEA) has been controversial. This study compared the outcomes of general anesthesia (GA) and local anesthesia (LA) in CEA. DESIGN: Systematic review and meta-analysis of comparative studies. SETTING: Hospitals. PARTICIPANTS: Adult patients undergoing CEA with either LA or GA. INTERVENTIONS: The effects of GA and LA on CEA outcomes were compared. MEASUREMENTS AND MAIN RESULTS: PubMed, OVID, Scopus, and Embase were searched to June 2018. Thirty-one studies with 152,376 patients were analyzed. A random effect model was used, and heterogeneity was assessed with the I2 and chi-square tests. LA was associated with shorter surgical time (weighted mean difference -9.15 min [-15.55 to -2.75]; p = 0.005) and less stroke (odds ratio [OR] 0.76 [0.62-0.92]; p = 0.006), cardiac complications (OR 0.59 [0.47-0.73]; p < 0.00001), and in-hospital mortality (OR 0.72 [0.59-0.90]; p = 0.003). Transient neurologic deficit rates were similar (OR 0.69 [0.46-1.04]; p = 0.07). Heterogeneity was significant for surgical time (I2 = 0.99, chi-square = 1,336.04; p < 0.00001), transient neurologic deficit (I2 = 0.41, chi-square = 28.81; p = 0.04), and cardiac complications (I2 = 0.42, chi-square = 43.32; p = 0.01) but not for stroke (I2 = 0.22, chi-square = 30.72; p = 0.16) and mortality (I2 = 0.00, chi-square = 21.69; p = 0.65). Randomized controlled trial subgroup analysis was performed, and all the aforementioned variables were not significantly different or heterogenous. CONCLUSION: The results from this study showed no inferiority of using LA to GA in patients undergoing CEA. Future investigations should be reported more systematically, preferably with randomization or propensity-matched analysis, and thus registries will facilitate investigation of this subject. Anesthetic choice in CEA should be individualized and encouraged where applicable.

Survey of epilepsy and seizure awareness in Manitoba: An evaluation.

BACKGROUND: Epilepsy and seizure awareness is gradually improving across Canada. With the strategic proposal for a Comprehensive Epilepsy Program in Manitoba (including formation of a new Pediatric Epilepsy Monitoring Unit (EMU)), a provincial strategy has been recommended outlining a path towards improved access to epilepsy care. We sought to qualify the current state of clinician knowledge and comfort towards diagnosis and management of this condition. METHODS: A qualitative online survey (Survey of Epilepsy and Seizure Awareness in Manitoba: An Evaluation (SESAME)), comprised of 36 short-answer questions, was delivered to primary care and specialist physicians in Manitoba. RESULTS: One hundred and eight subjects responded across varying medical disciplines. One hundred and one (93.5%) had previously managed patients with epilepsy, and 87 (80.6%) had previously ordered an electroencephalogram (EEG). A total of 63 (59.4%) had referred to a neurologist, with a lower proportion (30, 28.3%) referring specifically to an epileptologist. Only 36 respondents (33.3%) had heard of the International League Against Epilepsy (ILAE) guidelines. A total of 61 (56.5%) were unaware of invasive EEG techniques. Most (85, 78.7%) understood a role for surgery in treating epilepsy, with 12 (11.1%) unaware of surgical therapies beyond vagal nerve stimulation (VNS). Finally, less than half (44.2%) had heard about the Comprehensive Epilepsy Program in Manitoba, with nearly two-thirds (62.8%) indicating that they would like to have more information on epilepsy management. CONCLUSIONS: The SESAME successfully identified strong awareness towards epilepsy, with identifiable lapses in knowledge that will benefit from a formal provincial-wide educational curriculum.

Position Statement on the Use of Medical Cannabis for the Treatment of Epilepsy in Canada.

In Canada, recreational use of cannabis was legalized in October 2018. This policy change along with recent publications evaluating the efficacy of cannabis for the medical treatment of epilepsy and media awareness about its use have increased the public interest about this agent. The Canadian League Against Epilepsy Medical Therapeutics Committee, along with a multidisciplinary group of experts and Canadian Epilepsy Alliance representatives, has developed a position statement about the use of medical cannabis for epilepsy. This article addresses the current Canadian legal framework, recent publications about its efficacy and safety profile, and our understanding of the clinical issues that should be considered when contemplating cannabis use for medical purposes.

Énoncé de position quant à l'utilisation du cannabis médical dans le traitement de l'épilepsie. L'utilisation du cannabis à des fins récréatives a été légalisée au Canada en octobre 2018. Parallèlement à ce changement de politique, de récentes publication visant à évaluer l'efficacité du cannabis dans le traitement de l'épilepsie, de même qu'une sensibilisation médiatique accrue en ce qui concerne son utilisation, ont eu pour effet d'augmenter l'intérêt du grand public à son égard. Le Comité médical thérapeutique de la Ligue canadienne contre l'épilepsie (LCCE), de concert avec un groupe multidisciplinaire d'experts et des représentants de l'Alliance canadienne de l'épilepsie, a ainsi élaboré un énoncé de position en ce qui regarde l'utilisation du cannabis médical dans le traitement de l'épilepsie. Cet article entend donc aborder le cadre légal qui prévaut actuellement au Canada et examiner de récentes publications s'étant penchées sur le profil sécuritaire et sur l'efficacité du cannabis. De plus, nous voulons apporter un éclairage au sujet des aspects cliniques dont il faudrait tenir compte au moment d'envisager l'utilisation du cannabis à des fins médicales.

Perioperative Vasopressor Use in Free Flap Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: The use of vasopressors in free flap surgery has traditionally been avoided due to the presumed risk of pedicle vasospasm leading to flap failure. However, there is a lack of strong clinical evidence to suggest that their administration during microvascular surgery is absolutely contraindicated. The aim of this study is to clarify the impact of perioperative vasopressor use on free flap outcomes. METHODS: A systematic review was performed of all English-language articles that have compared free flap outcomes between patients who received vasopressors and those who did not. The outcome measures were total flap failure, pedicle thrombosis, and overall flap complications. Meta-analysis was performed using Mantel-Haenszel fixed-effects and DerSimonian and Laird random-effects models. RESULTS: From a total of 130 citations, 14 studies representing 8,653 cases were analyzed. Majority of these did not find any negative effects of vasopressor use irrespective of dose, timing of administration, and method of delivery. Meta-analysis demonstrated that vasopressors were associated with less total flap failure overall (odds ratio, [OR]: 0.71, p = 0.05) and less pedicle thrombosis in head and neck reconstruction specifically (OR: 0.58, p = 0.02). Flap complication rates were similar across all defect types (OR: 0.97, p = 0.81) but appeared to be increased in breast reconstruction (OR: 1.46, p = 0.01). CONCLUSION: Perioperative vasopressor administration does not appear to be as detrimental to free flap survival as has been previously feared. Their role in optimizing hemodynamic stability may have a more beneficial effect on overall flap perfusion and in minimizing the complications of iatrogenic fluid overload.

TMDIM: an improved algorithm for the structure prediction of transmembrane domains of bitopic dimers.

[Formula: see text]-Helical transmembrane proteins are the most important drug targets in rational drug development. However, solving the experimental structures of these proteins remains difficult, therefore computational methods to accurately and efficiently predict the structures are in great demand. We present an improved structure prediction method TMDIM based on Park et al. (Proteins 57:577-585, 2004) for predicting bitopic transmembrane protein dimers. Three major algorithmic improvements are introduction of the packing type classification, the multiple-condition decoy filtering, and the cluster-based candidate selection. In a test of predicting nine known bitopic dimers, approximately 78% of our predictions achieved a successful fit (RMSD <2.0 Å) and 78% of the cases are better predicted than the two other methods compared. Our method provides an alternative for modeling TM bitopic dimers of unknown structures for further computational studies. TMDIM is freely available on the web at https://cbbio.cis.umac.mo/TMDIM . Website is implemented in PHP, MySQL and Apache, with all major browsers supported.

Boosting the Performance of the Nickel Anode in the Oxygen Evolution Reaction by Simple Electrochemical Activation.

The development of cost-effective and active water-splitting electrocatalysts that work at mild pH is an essential step towards the realization of sustainable energy and material circulation in our society. Its success requires a drastic improvement in the kinetics of the anodic half-reaction of the oxygen evolution reaction (OER), which determines the overall system efficiency to a large extent. A simple electrochemical protocol has been developed to activate Ni electrodes, by which a stable NiOOH phase was formed, which could weakly bind to alkali-metal cations. The electrochemically activated (ECA) Ni electrode reached a current of 10 mA at <1.40 V vs. the reversible hydrogen electrode (RHE) at practical operation temperatures (>75 °C) and a mild pH of ca. 10 with excellent stability (>24 h), greatly surpassing that of the state-of-the-art NiFeOx electrodes under analogous conditions. Water electrolysis was demonstrated with ECA-Ni and NiMo, which required an iR-free overall voltage of only 1.44 V to reach 10 mA cmgeo-2 .

Sleep misperception in persons with epilepsy.

Being able to confidently ascertain the amount of sleep is critical to the clinical management of epilepsy. Sleep misperception is the phenomenon in which an individual underestimates the amount of time spent asleep. Little is known about sleep misperception in patients with epilepsy. We conducted retrospective chart reviews on individuals who self-identified as having epilepsy in a questionnaire database of patients undergoing polysomnography (PSG) at the Massachusetts General Hospital Sleep Laboratory. Our metric for sleep misperception was the difference between subjective and objective sleep latency (S-O SL) and subjective and objective total sleep time (S-O TST) with subjective values based on questionnaire and objective values based on PSG. We confirmed 64 patients with epilepsy. We then selected age- and sex-matched diagnostic PSG data for comparison from 50 patients with insomnia symptoms but no obstructive sleep apnea (OSA) and another 50 patients with OSA but no insomnia symptoms. In our cohort with epilepsy, the median SL overestimation was 20 min (p<0.05), and the median TST underestimation was 45 min (p<0.05). Sleep misperception was similar regardless of potential confounding factors such as categorical epilepsy refractoriness, cognitive impairment, or psychiatric comorbidity. Our findings suggest that sleep misperception occurs similarly in patients with epilepsy as in patients without epilepsy with insomnia. Our findings further support the potential clinical utility of objective PSG testing in patients with epilepsy, as this may not only identify occult OSA but also disclose sleep misperception.

A programmable hybrid digital chemical information processor based on the Belousov-Zhabotinsky reaction.

The exponential growth of the power of modern digital computers is based upon the miniaturization of vast nanoscale arrays of electronic switches, but this will be eventually constrained by fabrication limits and power dissipation. Chemical processes have the potential to scale beyond these limits by performing computations through chemical reactions, yet the lack of well-defined programmability limits their scalability and performance. Here, we present a hybrid digitally programmable chemical array as a probabilistic computational machine that uses chemical oscillators using Belousov-Zhabotinsky reaction partitioned in interconnected cells as a computational substrate. This hybrid architecture performs efficient computation by distributing information between chemical and digital domains together with inbuilt error correction logic. The efficiency is gained by combining digital logic with probabilistic chemical logic based on nearest neighbour interactions and hysteresis effects. We demonstrated the computational capabilities of our hybrid processor by implementing one- and two-dimensional Chemical Cellular Automata demonstrating emergent dynamics of life-like entities called Chemits. Additionally, we demonstrate hybrid probabilistic logic as a viable logic for solving combinatorial optimization problems.