Development of an International Standard Set of Outcomes and Measurement Methods for Routine Practice for Infants, Children, and Adolescents with Epilepsy: The International Consortium for Health Outcomes Measurement Consensus Recommendations.

At present, there is no internationally accepted set of core outcomes or measurement methods for epilepsy clinical practice. The International Consortium for Health Outcomes Measurement (ICHOM) convened an international working group of experts in epilepsy, people with epilepsy, and their representatives to develop minimum sets of standardized outcomes and outcome measurement methods for clinical practice. Using modified Delphi consensus methods with consecutive rounds of online voting over 12 months, a core set of outcomes and corresponding measurement tool packages to capture the outcomes were identified for infants, children, and adolescents with epilepsy. Consensus methods identified 20 core outcomes. In addition to the outcomes identified for the ICHOM Epilepsy adult standard set, behavioral, motor, and cognitive/language development outcomes were voted as essential for all infants and children with epilepsy. The proposed set of outcomes and measurement methods will facilitate the implementation of the use of patient-centered outcomes in daily practice.

Development of an International Standard Set of Outcomes and Measurement Methods for Routine Practice for Adults with Epilepsy: The International Consortium for Health Outcomes Measurement Consensus Recommendations.

At present, there is no internationally accepted set of core outcomes or measurement methods for epilepsy clinical practice. Therefore, the International Consortium for Health Outcomes Measurement (ICHOM) convened an international working group of experts in epilepsy, people with epilepsy and their representatives to develop minimum sets of standardized outcomes and outcomes measurement methods for clinical practice that support patient-clinician decision-making and quality improvement. Consensus methods identified 20 core outcomes. Measurement tools were recommended based on their evidence of strong clinical measurement properties, feasibility, and cross-cultural applicability. The essential outcomes included many non-seizure outcomes: anxiety, depression, suicidality, memory and attention, sleep quality, functional status, and the social impact of epilepsy. The proposed set will facilitate the implementation of the use of patient-centered outcomes in daily practice, ensuring holistic care. They also encourage harmonization of outcome measurement, and if widely implemented should reduce the heterogeneity of outcome measurement, accelerate comparative research, and facilitate quality improvement efforts.

Adverse Events and Complications Associated With Vagal Nerve Stimulation: An Analysis of the Manufacturer And User Facility Device Experience Database.

OBJECTIVE: Drug-resistant epilepsy (DRE) can have devastating consequences for patients and families. Vagal nerve stimulation (VNS) is used as a surgical adjunct for treating DRE not amenable to surgical resection. Although VNS is generally safe, it has its inherent complications. With the increasing number of implantations, adequate patient education with discussion of possible complications forms a critical aspect of informed consent and patient counseling. There is a lack of large-scale reviews of device malfunction, patient complaints, and surgically related complications available to date. MATERIALS AND METHODS: Complications associated with VNS implants performed between 2011 and 2021 were identified through a search of the United States Food and Drug Administration Manufacturer And User Facility Device Experience (MAUDE) data base. We found three models on the data base, CYBERONICS, INC pulse gen Demipulse 103, AspireSR 106, and SenTiva 1000. The reports were classified into three main groups, "Device malfunction," "Patient complaints," and "Surgically managed complications." RESULTS: A total of 5888 complications were reported over the ten-year period, of which 501 reports were inconclusive, 610 were unrelated, and 449 were deaths. In summary, there were 2272 reports for VNS 103, 1526 reports for VNS 106, and 530 reports for VNS 1000. Within VNS 103, 33% of reports were related to device malfunction, 33% to patient complaints, and 34% to surgically managed complications. For VNS 106, 35% were related to device malfunction, 24% to patient complaints, and 41% to surgically managed complications. Lastly, for VNS 1000, 8% were device malfunction, 45% patient complaints, and 47% surgically managed complications. CONCLUSION: We present an analysis of the MAUDE data base for adverse events and complications related to VNS. It is hoped that this description of complications and literature review will help promote further improvement in its safety profile, patient education, and management of both patient and clinician expectations.

Parents' priorities for decision-making of pediatric epilepsy treatments and perceived needs for decision support in multi-ethnic Asian clinical setting: A qualitative analysis.

OBJECTIVE: To identify parents' priorities when making a decision on genetic testing and antiseizure drug (ASD) options for pediatric epilepsy and their support needs for informed decision-making in multi-ethnic Asian clinical settings. METHODS: Qualitative in-depth interviews, using a semi-structured interview guide, were conducted with purposively selected parents of pediatric patients with newly diagnosed epilepsy or known diagnosis of epilepsy (n = 26). Interviews were audio recorded and transcribed verbatim. Thematic analysis was undertaken to generate themes. RESULTS: Parents' narratives showed difficulty assimilating information, while knowledge deficit and emotional vulnerability led parents' desire to defer a decision for testing and ASDs to mitigate decisional burden. Priorities for decisions were primarily based on intuitive ideas of the treatment's risks and benefits, yet very few could elaborate on tradeoffs between risks and efficacy. Priorities outside the purview of the healthcare team, such as children's emotional wellbeing and family burden of ASD administration, were also considered important. Authority-of-medical-professional heuristic facilitated the ASD decision for parents who preferred shared rather than sole responsibility for a decision. Importantly, parents' support needs for informed decision-making were very much related to the availability of support mechanisms in post-treatment decisions owing to perceived uncertainty of the chosen ASD. CONCLUSIONS: Findings suggest that multiple priorities influenced ASD decision process. To address support needs of parents for informed decision-making, more consideration should be given to post-treatment decision support through the provision of educational opportunities, building peer support networks, and developing a novel communication channel between healthcare providers and parents.

Neurology of the H1N1 pandemic in Singapore: a nationwide case series of children and adults.

Neurologic complications have long been associated with influenza. A novel strain of influenza A (H1N1) first described in humans to have outbreak potential in 2009 in Mexico went on to become the first influenza pandemic of this century. We evaluated the neurologic complications of the novel influenza A (H1N1) 2009 in children and adults admitted to all public hospitals in Singapore during the influenza A (H1N1) 2009 pandemic between May 2009 and March 2010. All patients were positive for novel H1N1 infection and presented with neurologic symptoms prior to oseltamivir treatment. Ninety-eight patients (median age 6.6 years, range 0.4-62.6) were identified; 90 % were younger than 18 years; 32 % suffered from preexisting neurological, respiratory, or cardiac disease; and 66 % presented with seizures. Of those presenting with seizures, new onset seizures were the most common manifestation (n = 40, 61.5 %), followed by breakthrough seizures (n = 18, 27.7 %) and status epilepticus (n = 7, 10.8 %). Influenza-associated encephalopathy occurred in 20 %. The majority of children (n = 88) presented with seizures (n = 63, 71.6 %), encephalopathy (n = 19, 21.6 %), and syncope (n = 4, 4.5 %). Among adults, a wider range of neurological conditions were seen, with half of them presenting with an exacerbation of their underlying neurological disease. The neurological symptoms developed at a median of 2 days after the onset of systemic symptoms. The median length of hospital stay was 3 days, and 79 % were monitored in general wards. Neurologic complications associated with the novel influenza A (H1N1) 2009 strain were generally mild and had a good outcome. They occurred more frequently in patients with underlying neurological disorders. Seizures and encephalopathy were the most common manifestations, similar to other influenza virus strains.

Role of Perampanel in the Management of Pediatric Epilepsies in Asia: Expert Opinion.

Management of pediatric epilepsies poses unique challenges around diagnosis, treatment options, comorbidities, and the potential for these factors to interact with processes in the developing brain. In pediatric patients, broad-spectrum antiseizure medications (ASMs) with minimal potential for adverse events (AEs) and limited impact on cognition and behavior are preferred. Perampanel is a first-in-class ASM with broad-spectrum efficacy, a tolerable safety profile, minimal negative impact on cognitive function, and other features that make it a viable treatment option in this patient population. However, evidence and experience of its use in pediatric patients are less extensive than in adult patients. Experts in pediatric epilepsy across the region convened at a series of meetings to discuss the use of perampanel in pediatric patients, including dose optimization, AE prevention and management, and considerations in particular groups. This article summarizes key evidence for perampanel in the pediatric population and consolidates the experts' recommendations for using the ASM in managing pediatric epilepsies.

Developing a nomogram for dose individualization of phenytoin in Asian pediatric patients derived from population pharmacokinetic modeling of saturable pharmacokinetic profiles of the drug.

BACKGROUND: A population pharmacokinetic model for phenytoin in Asian pediatric patients was developed to determine the influence of concurrent medications, patient demographics, and blood biochemistry on the pharmacokinetic profile of phenytoin. METHODS: Retrospective clinical data were obtained from 66 patients (age, 1-16 years) for the determination of pharmacokinetic parameters of phenytoin using WinNonmix. Data from 49 patients (74.2%) were allocated in the "index" group, and the other 17 patients (25.8%) in the "validation" group. Models were compared by final log likelihood, mean error as a measure of bias, and root-mean-squared error as a measure of precision. RESULTS: The Michaelis-Menten constant (km) and volume of distribution (V) were fixed at 9.08 mg/L and 1.23 L/kg, respectively. The saturated elimination rate (V × Vmax) of phenytoin was then found to be 0.525 mg/kg per hour (352.9 4 mg/d for a 28.0 kg individual). Patients' body surface area (in square meter) and catalytic activities of liver enzymes aspartate aminotransferase (U/L) and alkaline phosphatase (U/L) appeared to have significant correlation with Vmax, whereas coadministrating drugs with phenytoin did not yield any significant effect. The final model for the saturated elimination rate was (Equation is included in full-text article.) In validation of the final model, the mean error was found to be -0.805 (95% confidence interval, -3.67 to 2.06), and the root-mean-squared error was 7.92 (95% confidence interval, 3.41-12.43). CONCLUSIONS: The obtained results indicated the need to consider patients' body surface area and the catalytic activities of liver enzymes aspartate aminotransferase and alkaline phosphatase when dosing phenytoin. Based on the population pharmacokinetic parameters, a nomogram was subsequently developed for dose individualization of phenytoin in Asian pediatric patients.

A retrospective study on the usage of antiepileptic drugs in Asian children from 2000 to 2009 in the largest pediatric hospital in Singapore.

PURPOSE: In light of the increasing usage of the newer antiepileptic drugs (AEDs) in other countries, we reviewed the prescribing pattern of AEDs in Singapore over the last 10 years (2000-2009). METHODS: A retrospective review of pharmacy dispensing records solicited from the only children's hospital in Singapore was performed to analyze the trend in AEDs prescribing in the last 10 years. We also examined the correlation between the serum concentrations of valproic acid (VPA), the most-prescribed AED, and seizure control. Descriptive and inferential statistical analyses were then performed on the findings. RESULTS: A total of 41 671 prescriptions on AEDs were retrieved and analyzed. Despite the introduction of the second-generation AEDs, the first generation AEDs still dominate epilepsy treatment in Asian children, with VPA being the mostly prescribed AED (about 40% of the total AEDs usage). The majority of patients (62.8%) were on monotherapy. The mean VPA serum concentration in patients with good seizure control was 68.6 µg/ml (SD = 26.4 µg/ml; range = 12.2-138.0 µg/ml), which was statistically higher than the mean VPA concentration of 57.7 µg/ml (SD = 27.1 µg/ml; range = 11.1-149.0 µg/ml) in patients with poor seizure control (p < 0.0001). CONCLUSION: With VPA being the most prescribed AED in our clinical practice, and the finding in this study that with careful classification of the patients' condition, serum concentrations of VPA generally correlate well with the seizure control, the correct dose titration of VPA with therapeutic drug monitoring is still of paramount importance.

Comparison of functional outcome scales in paediatric acute encephalitis: Responsiveness and outcome predictors.

PURPOSE: To compare scoring systems and their ability to capture short and long-term recovery of paediatric patients with acute encephalitis. To identify clinical predictors of short-term outcomes by correlating functional outcome measures at 1 month post diagnosis of acute encephalitis. METHODS: Patients with encephalitis diagnosed between July 2011 and 2016 based on Granerod's criteria were studied in this retrospective cohort study. Functional outcome scores on WeeFIM, LOS, GOS-E, mRS and ICF at initial presentation and 1, 3, 6 and 12 months later were compared. RESULTS: WeeFIM and LOS scores both showed maximum change in the first 3 months, reflecting highest recovery in this period. With WeeFIM, the greatest change occurred within the first month following diagnosis. On univariate analysis, seizure frequency in the first month, presence of movement disorder, presence of autonomic dysfunction and lower baseline functional score was associated with poorer WeeFIM scores at 1 month. The latter three variables remained statistically significant on multivariate analysis. CONCLUSION: WeeFIM is a potentially preferred functional outcome assessment tool as it demonstrated greatest recovery within the first month due to a trend of high responsiveness and relatively low ceiling effect. Presence of autonomic dysfunction and movement disorders at diagnosis correlated with poorer outcome at 1 month post diagnosis.

Single-cell transcriptomics and surface epitope detection in human brain epileptic lesions identifies pro-inflammatory signaling.

Epileptogenic triggers are multifactorial and not well understood. Here we aimed to address the hypothesis that inappropriate pro-inflammatory mechanisms contribute to the pathogenesis of refractory epilepsy (non-responsiveness to antiepileptic drugs) in human patients. We used single-cell cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) to reveal the immunotranscriptome of surgically resected epileptic lesion tissues. Our approach uncovered a pro-inflammatory microenvironment, including extensive activation of microglia and infiltration of other pro-inflammatory immune cells. These findings were supported by ligand-receptor (LR) interactome analysis, which demonstrated potential mechanisms of infiltration and evidence of direct physical interactions between microglia and T cells. Together, these data provide insight into the immune microenvironment in epileptic tissue, which may aid the development of new therapeutics.

Topographic movie of intracranial ictal high-frequency oscillations with seizure semiology: epileptic network in Jacksonian seizures.

PURPOSE: We developed a technique to produce images of dynamic changes in ictal high-frequency oscillations (HFOs) >40 Hz recorded on subdural electroencephalography (EEG) that are time-locked to the ictal EEG and ictal semiology video. We applied this technique to Jacksonian seizures to demonstrate ictal HFO propagation along the homunculus in the primary sensory-motor cortex to visualize the underlying epileptic network. METHODS: We analyzed intracranial ictal EEGs from two patients with intractable Jacksonian seizures who underwent epilepsy surgery. We calculated the degrees of increase in amplitude within 40-80, 80-200, and 200-300 Hz frequency bands compared to the interictal period and converted them into topographic movies projected onto the brain surface picture. We combined these data with the ictal EEGs and video of the patient demonstrating ictal semiology. KEY FINDINGS: The ictal HFOs began in the sensory cortex and appeared concomitantly with the sensory aura. They then propagated to the motor cortex at the same time that focal motor symptoms evolved. As the seizure progressed, the ictal HFOs spread or reverberated in the rolandic region. However, even when the seizure became secondarily generalized, the ictal HFOs were confined to the rolandic region. In both cases, there was increased amplitude of higher frequency bands during seizure initiation compared to seizure progression. SIGNIFICANCE: This combined movie showed the ictal HFO propagation corresponding to the ictal semiology in Jacksonian seizures and revealed the epileptic network involved in seizure initiation and progression. This method may advance understanding of neural network activities relating to clinical seizure generation and propagation.

Recollection of pain due to inappropriate versus appropriate implantable cardioverter-defibrillator shocks.

BACKGROUND: Although inappropriate shocks are known to be an important consequence of implantable cardioverter-defibrillators (ICDs), the subjective experience of pain intensity perceived by those receiving inappropriate versus appropriate shocks has not previously been examined. METHODS: One hundred ICD patients underwent a standardized interview by an investigator blinded to the clinical history. Patients with a previous ICD shock were asked to describe the intensity of the associated pain on a standard 0-10 scale (10 being the worst pain they had ever experienced). Medical charts were then examined for any history of inappropriate and/or appropriate ICD discharges. RESULTS: Thirty-five of the 100 patients had a record of at least one ICD shock, and 17 had experienced at least one inappropriate shock. Those with a history of an inappropriate shock described a significantly higher median pain scale (9, interquartile range [IQR] 8-10) compared to those with a history of only appropriate shocks (median 4, IQR 2-8, P = 0.0011). In multivariable analysis, a history of an inappropriate shock was the only predictor statistically significantly associated with an increase in shock pain: the pain scale for those with inappropriate shocks was higher by 2.8 points on average after multivariable adjustment (95% confidence interval 0.29-5, P = 0.030). Eighteen patients had considered having their device deactivated, and a history of an inappropriate shock was the only factor independently associated with this consideration. CONCLUSIONS: Compared to those who have received only appropriate shocks, inappropriate ICD shocks are associated with a recollection of greater pain and consideration of device inactivation.

Causes, functional outcomes and healthcare utilisation of people with cerebral palsy in Singapore.

INTRODUCTION: A voluntary cerebral palsy (CP) registry was established in 2017 to describe the clinical characteristics and functional outcomes of CP in Singapore. METHODS: People with CP born after 1994 were recruited through KK Women's and Children's Hospital, National University Hospital and Cerebral Palsy Alliance Singapore. Patient-reported basic demographics, service utilisation and quality of life measures were collected with standardised questionnaires. Clinical information was obtained through hospital medical records. RESULTS: Between 1 September 2017 and 31 March 2020, 151 participants were recruited. A majority (n=135, 89%) acquired CP in the pre/perinatal period, where prematurity (n=102, 76%) and the need for emergency caesarean section (n=68, 50%) were leading risk factors. Sixteen (11%) of the total participants had post-neonatally acquired CP. For predominant CP motor types, 109 (72%) had a spastic motor type; 32% with spastic mono/hemiplegia, 41% diplegia, 6% triplegia and 21% quadriplegia. The remaining (42, 27.8%) had dyskinetic CP. Sixty-eight (45.0%) participants suffered significant functional impairment (Gross Motor Functional Classification System levels IV-V). Most participants (n=102, 67.5%) required frequent medical follow-up (≥4 times a year). CONCLUSION: Optimisation of pre- and perinatal care to prevent and manage prematurity could reduce the burden of CP and their overall healthcare utilisation.

Genetic landscape of congenital disorders in patients from Southeast Asia: results from sequencing using a gene panel for Mendelian phenotypes.

OBJECTIVE: To test the utility and diagnostic yield of a medical-exome gene panel for identifying pathogenic variants in Mendelian disorders. METHODS: Next-generation sequencing was performed with the TruSight One gene panel (targeting 4813 genes) followed by MiSeq sequencing on 216 patients who presented with suspected genetic disorders as assessed by their attending physicians. RESULTS: There were 56 pathogenic and 36 likely pathogenic variants across 57 genes identified in 87 patients. Causal mutations were more likely to be truncating and from patients with a prior clinical diagnosis. Another 18 promising variants need further evaluation for more evidence to meet the requirement for potential upgrade to pathogenic. Forty-five of the 92 clinically significant variants were novel. CONCLUSION: The 40.3% positive yield compares favourably with similar studies using either this panel or whole exome sequencing, demonstrating that large gene panels could be a good alternative to whole exome sequencing for quick genetic confirmation of Mendelian disorders.

Hospital-based observational study of neurological disorders in patients recently vaccinated with COVID-19 mRNA vaccines.

PURPOSE: We describe the spectrum of acute neurological disorders among hospitalized patients who recently had COVID-19 mRNA vaccination. METHOD: We performed a prospective study at 7 acute hospitals in Singapore. Hospitalized patients who were referred for neurological complaints and had COVID-19 mRNA vaccines, BNT162b2 and mRNA-1273, in the last 6 weeks were classified into central nervous system (CNS) syndromes, cerebrovascular disorders, peripheral nervous system (PNS) disorders, autonomic nervous system (ANS) disorders and immunization stress-related responses (ISRR). RESULTS: From 30 December 2020 to 20 April 2021, 1,398,074 persons (median age 59 years, 54.5% males) received COVID-19 mRNA vaccine (86.7% BNT162b2, 13.3% mRNA-1273); 915,344(65.5%) completed 2 doses. Four hundred and fifty-seven(0.03%) patients were referred for neurological complaints [median age 67(20-97) years, 281(61.5%) males; 95.8% received BNT162b2 and 4.2% mRNA-1273], classified into 73(16.0%) CNS syndromes, 286(62.6%) cerebrovascular disorders, 59(12.9%) PNS disorders, 0 ANS disorders and 39(8.5%) ISRRs. Eleven of 27 patients with cranial mononeuropathy had Bell's palsy. Of 33 patients with seizures, only 4 were unprovoked and occurred within 2 weeks of vaccination. All strokes occurred among individuals with pre-existing cardiovascular risk factors. We recorded 2 cases of cerebral venous thrombosis; none were vaccine-induced thrombotic thrombocytopenia. Five had mild flares of immune-mediated diseases. CONCLUSION: Our observational study does not establish causality of the described disorders to vaccines. Though limited by the lack of baseline incidence data of several conditions, we observed no obvious signal of serious neurological morbidity associated with mRNA vaccination. The benefits of COVID-19 vaccination outweigh concerns over neurological adverse events.

Assessment of the Understanding of Concussion and Care Protocols Amongst Student Athletes and Coaches: A Qualitative Study.

Background: Pediatric sports-induced concussions have become a topic of interest and concern in the scientific community. Already, the literature is rich with studies that have identified numerous short-term and long-term consequences of childhood sports-induced concussions. However, there are very few studies that have identified how well the students who participate in concussion-prone sports and their coaches understand these consequences and how they can be avoided. This study aimed to explore student athletes' and their coaches' understanding of the concept of concussion and how it is managed both immediately after the injury occurs and during long-term recovery. Methods: This study utilized a qualitative design. The study was conducted in local and international schools in Singapore. Participants were recruited through purposive sampling. 42 student athletes aged 13-18 who participated in rugby, softball, football, cricket, volleyball, and/or water polo were recruited. Fourteen coaches who coached these same sports were also recruited. Four focus groups and three semi-structured interviews were conducted. Data collected were then analyzed with thematic analysis. Risk factors were assessed through four domains of focus: understanding of what concussion is; attitudes toward concussion; existing protocols for treating concussion; and return-to-school and return-to-play protocols. As this is a qualitative study, outcome measures were not identified. Results: Analysis of the data revealed four themes for each group. For student-athletes these included: limited understanding of concussion; non-reporting of injuries; variable supervision of athletes; and a lack of established return-to-school and return-to-play guidelines. For coaches these included: variable understanding of concussion; insufficient formal training in concussion management; limited medical support in managing injuries; and lack of understanding and adherence to return-to-school and return-to-play protocols. Conclusions: Of the themes identified, the most pressing was a lack of clearly defined return-to-play guidelines. This is an urgent issue that needs to be jointly addressed by healthcare professionals and schools with evidence-based guidelines.

Right middle cerebral artery infarct after minor head trauma in an infant: Case report and literature review.

Ishaemic stroke (IS) in the paediatric population is extremely rare. In this age group, the occurrence of IS often concurs with underlying congenital heart disease, haematological, metabolic or immunological conditions. In contrast, the association between IS and minor head injury in children has been sparse in current literature. The authors report a case of a healthy 9-month-old male who was found to have a right middle cerebral artery territory infarct after a minor head injury. An extensive medical workup was performed, and it was negative for any previously undiagnosed co-morbidities. Given the paucity of such cases, the condition and its management are discussed in corroboration with current literature.

Underutilization of epilepsy surgery in ASEAN countries.

PURPOSE: This survey was performed to determine the availability of epilepsy surgery, and understand the limiting factors to epilepsy surgery in ASEAN countries with total of 640 million population. METHOD: A cross-sectional survey was completed by national representatives in all ASEAN countries (Brunei, Cambodia, East Timor, Indonesia, Laos, Malaysia, Myanmar, Philippines, Singapore, Thailand, and Vietnam). RESULTS: Overall facilities for initial epilepsy pre-surgical evaluation are available in most countries, but further non-invasive and invasive investigations are limited. Three countries (Brunei, Cambodia, and East Timor) have no epilepsy center, and 2 countries (Laos, Myanmar) have level 2 centers doing tumor surgery only. Level-3 epilepsy centers are available in 6 countries (Indonesia, Malaysia, Philippine, Singapore, Thailand, Vietnam); only 5 countries (Indonesia, Malaysia, Philippine, Singapore, Thailand) has at least one level-4 epilepsy care facility. Indonesia with 261 million population only has one level 3 and another level 4 center. The costs of presurgical evaluation and brain surgery vary within and among the countries. The main barriers towards epilepsy surgery in ASEAN include lack of expertise, funding and facilities. CONCLUSIONS: Epilepsy surgery is underutilized in ASEAN with low number of level 3 centers, and limited availability of advanced presurgical evaluation. Lack of expertise, facilities and funding may be the key factors contributing to the underutilization.

Spatially filtered magnetoencephalography compared with electrocorticography to identify intrinsically epileptogenic focal cortical dysplasia.

This study was carried out to evaluate Synthetic Aperture Magnetometry-kurtosis (SAM(g(2))), a spatially filtered source localization technique in magnetoencephalography (MEG), for identification of epileptogenic areas of focal cortical dysplasia (FCD). Three children with FCD were investigated to localize the ictal onset zone (IOZ). All patients subsequently had extraoperative electrocorticography (ECoG) for intractable epilepsy and surgical resection. SAM(g(2)) analysis showed overlapping of interictal MEG spike sources with the IOZ on ECoG in all children. We recommend MEG-SAM(g(2)) and MEG interictal spike source localization in patients with epileptogenic FCD.

Utility of the Seattle Heart Failure Model for palliative care referral in advanced ambulatory heart failure.

BACKGROUND: Physicians face uncertainty when predicting death in heart failure (HF) leading to underutilisation of palliative care. To facilitate decision-making, we assessed the Seattle Heart Failure Model (SHFM) as a referral tool by evaluating its performance in predicting 1-year event-free survival from death, heart transplant (HTx), and ventricular assist device (VAD) implantation. METHODS: We retrospectively reviewed the charts of consecutive patients with advanced ambulatory HF with New York Heart Association Class III/IV HF and a left ventricular ejection fraction of ≤40% from 2000 to 2016. We evaluated SHFM's performance by using the Cox proportional hazards model, its discrimination using the c-statistic, its calibration by comparing the observed and predicted survival and its clinical utility by hypothetically assessing the proportion of patients adequately or inadequately referred to palliative care. RESULTS: We included 612 patients in our study. During the 1-year follow-up, there were 83 deaths, 4 HTx and 1 VAD. Although SHFM showed very good discrimination (c-statistic=0.71) and adequate calibration in medium to low-risk patients, it underestimated event-free survival by 12% in high-risk patients. SHFM's clinical utility was limited: 33% of eligible patients would have missed the opportunity for referral and only 27% of referred patients would have benefited. CONCLUSION: Use of SHFM could result in a high proportion of referrals while capturing the majority of patients who may benefit from palliative care. Though this may be a more encompassing and safer alternative than current referral practices, it could lead to many early referrals.