Implications of Large Language Models for Quality and Efficiency of Neurologic Care: Emerging Issues in Neurology.

Large language models (LLMs) are advanced artificial intelligence (AI) systems that excel in recognizing and generating human-like language, possibly serving as valuable tools for neurology-related information tasks. Although LLMs have shown remarkable potential in various areas, their performance in the dynamic environment of daily clinical practice remains uncertain. This article outlines multiple limitations and challenges of using LLMs in clinical settings that need to be addressed, including limited clinical reasoning, variable reliability and accuracy, reproducibility bias, self-serving bias, sponsorship bias, and potential for exacerbating health care disparities. These challenges are further compounded by practical business considerations and infrastructure requirements, including associated costs. To overcome these hurdles and harness the potential of LLMs effectively, this article includes considerations for health care organizations, researchers, and neurologists contemplating the use of LLMs in clinical practice. It is essential for health care organizations to cultivate a culture that welcomes AI solutions and aligns them seamlessly with health care operations. Clear objectives and business plans should guide the selection of AI solutions, ensuring they meet organizational needs and budget considerations. Engaging both clinical and nonclinical stakeholders can help secure necessary resources, foster trust, and ensure the long-term sustainability of AI implementations. Testing, validation, training, and ongoing monitoring are pivotal for successful integration. For neurologists, safeguarding patient data privacy is paramount. Seeking guidance from institutional information technology resources for informed, compliant decisions, and remaining vigilant against biases in LLM outputs are essential practices in responsible and unbiased utilization of AI tools. In research, obtaining institutional review board approval is crucial when dealing with patient data, even if deidentified, to ensure ethical use. Compliance with established guidelines like SPIRIT-AI, MI-CLAIM, and CONSORT-AI is necessary to maintain consistency and mitigate biases in AI research. In summary, the integration of LLMs into clinical neurology offers immense promise while presenting formidable challenges. Awareness of these considerations is vital for harnessing the potential of AI in neurologic care effectively and enhancing patient care quality and safety. The article serves as a guide for health care organizations, researchers, and neurologists navigating this transformative landscape.

Screening for Quality of Life in a Neurology Tic Clinic Using Quality Improvement Methodology.

BACKGROUND: Tic disorders in children often co-occur with other disorders that can significantly impact functioning. Screening for quality of life (QoL) can help identify optimal treatment paths. This quality improvement (QI) study describes implementation of a QoL measure in a busy neurology clinic to help guide psychological intervention for patients with tics. METHODS: Using QI methodology outlined by the Institute for Healthcare Improvement, this study implemented the PedsQL Generic Core (4.0) in an outpatient medical clinic specializing in the diagnosis and treatment of tic disorders. Assembling a research team to design process maps and key driver diagrams helped identify gaps in the screening process. Conducting several plan-do-study-act cycles refined identification of patients appropriate to receive the measure. Over the three-year study, electronic health record notification tools and data collection were increasingly utilized to capture patients' information during their visit. RESULTS: Over 350 unique patients were screened during the assessment period. Electronic means replaced paper measures as time progressed. The percentage of patients completing the measure increased from 0% to 51.9% after the initial implementation of process improvement, advancing to 91.6% after the introduction of electronic measures. This average completion rate was sustained for 15 months. CONCLUSIONS: Using QI methodology helped identify the pragmatics of implementing a QoL assessment to enhance screening practices in a busy medical clinic. Assessment review at the time of appointment helped inform treatment and referral decisions.

Dual catheter and double-lumen cerebrospinal fluid shunt systems with backflow mechanisms.

PURPOSE: We previously developed a novel functional benchtop apparatus to simulate catheter occlusion in vitro utilizing avian vitelline membrane and chalaza to test catheter designs and de-obstruction techniques. Here, we study the integration of double-lumen catheter-mediated backflow in the shunt system assembly and its potential for an in-line de-obstruction of an obstructed ventricular catheter. METHODS: A double-lumen catheter was connected to a standard proximal shunt catheter for all trials. One limb of the double-lumen catheter was connected to the backflow mechanisms and allowed to loop back for fluid access. A micropump and a bi-corporal electromagnetic pump were utilized to provide various degrees of backflow at predetermined intervals. Flow rates were measured after initial occlusion and after implementation of the backflow mechanisms, and degrees of catheter blockage was calculated as a percentage of the unoccluded flow rate. Flow visualization was also used. RESULTS: In baseline blockage of less than 50%, the average occluding agent weighed 0.3-0.6 g with baseline flow rates of 8.5-11.9 mL/min. After 5 min of backflow using a micropump, the degree of blockage was reduced in 50% of trials. Additional backflow for 5 min did not provide further improvements in flow rate. In baseline blockage of greater than 50%, the average occluding agent weighed 0.8-1.3 g with baseline flow rates of 1.1-4.2 mL/min. After 5 min of backflow, the system demonstrated a decreased blockage in 20% of trials; additional backflow for 5 min further improved the flow rate in 40% of the total trials. Only magnetic plates provided enough force to provide pulsatile backflow in the bi-corporal electromagnetic system. CONCLUSIONS: The preliminary results of connecting a standard proximal catheter in series with a double-lumen catheter show a slight change in the percent occlusion from the baseline status several times when the retrograde flow occurred via one limb of the catheter. Additionally, the de-obstruction seems related to the length of the interval of the backflow and the initial percentage occlusion of the proximal catheter. The statistical analysis does not reveal a statistically significant reduction in occlusion in the proximal catheter with either backflow interval.

Severe communication delays are independent of seizure burden and persist despite contemporary treatments in SCN1A+ Dravet syndrome: Insights from the ENVISION natural history study.

OBJECTIVE: Dravet syndrome (DS) is a developmental and epileptic encephalopathy characterized by high seizure burden, treatment-resistant epilepsy, and developmental stagnation. Family members rate communication deficits among the most impactful disease manifestations. We evaluated seizure burden and language/communication development in children with DS. METHODS: ENVISION was a prospective, observational study evaluating children with DS associated with SCN1A pathogenic variants (SCN1A+ DS) enrolled at age ≤5 years. Seizure burden and antiseizure medications were assessed every 3 months and communication and language every 6 months with the Bayley Scales of Infant and Toddler Development 3rd edition and the parent-reported Vineland Adaptive Behavior Scales 3rd edition. We report data from the first year of observation, including analyses stratified by age at Baseline: 0:6-2:0 years:months (Y:M; youngest), 2:1-3:6 Y:M (middle), and 3:7-5:0 Y:M (oldest). RESULTS: Between December 2020 and March 2023, 58 children with DS enrolled at 16 sites internationally. Median follow-up was 17.5 months (range = .0-24.0), with 54 of 58 (93.1%) followed for at least 6 months and 51 of 58 (87.9%) for 12 months. Monthly countable seizure frequency (MCSF) increased with age (median [minimum-maximum] = 1.0 in the youngest [1.0-70.0] and middle [1.0-242.0] age groups and 4.5 [.0-2647.0] in the oldest age group), and remained high, despite use of currently approved antiseizure medications. Language/communication delays were observed early, and developmental stagnation occurred after age 2 years with both instruments. In predictive modeling, chronologic age was the only significant covariate of seizure frequency (effect size = .52, p = .024). MCSF, number of antiseizure medications, age at first seizure, and convulsive status epilepticus were not predictors of language/communication raw scores. SIGNIFICANCE: In infants and young children with SCN1A+ DS, language/communication delay and stagnation were independent of seizure burden. Our findings emphasize that the optimal therapeutic window to prevent language/communication delay is before 3 years of age.

Implementing American Academy of Neurology Quality Measures in Antigua Using Quality Improvement Methodology.

Background and Objectives: The American Academy of Neurology has developed quality measures related to various neurologic disorders. A gap exists in the implementation of these measures in the different health care systems. To date, there has been no electronic health care record nor implementation of quality measures in Antigua. Therefore, we aimed to increase the percent of patients who have epilepsy quality measures documented using standardized common data elements in the outpatient neurology clinic at Sir Lester Bird Medical Center from 0% to 80% per week by June 1, 2022 and sustain for 6 months. Methods: We used the Institute for Health care Improvement Model for Improvement methodology. A data use agreement was implemented. Data were displayed using statistical process control charts and the American Society for Quality criteria to determine statistical significance and centerline shifts. Results: Current and future state process maps were developed to determine areas of opportunity for interventions. Interventions were developed following a "Plan-Do-Study-Act cycle." One intervention was the creation of a RedCap survey and database to be used by health care providers during clinical patient encounters. Because of multiple interventions, we achieved a 100% utilization of the survey for clinical care. Discussion: Quality improvement (QI) methodology can be used for implementation of quality measures in various settings to improve patient care outcomes without use of significant resources. Implementation of quality measures can increase efficiency in clinical delivery. Similar QI methodology could be implemented in other resource-limited countries of the Caribbean and globally.

Patient family engagement and partnership: Pilot survey results in assessing behavior, communication, and quality of life in children with Lennox-Gastaut syndrome and other drug-resistant epilepsy.

OBJECTIVES: Lennox-Gastaut Syndrome (LGS) and other drug-resistant epilepsy (DRE) can impact behavior, communication, and quality of life (QoL). In collaboration with community engagement efforts with the Lennox-Gastaut Syndrome Foundation (LGSF), we aimed to gain an initial snapshot of patient and family perspectives and experiences with evaluation of behavior, communication, and QoL. METHODS: A cross-sectional survey was conducted to collect self-reported information from caregivers of children with LGS and other DRE regarding their perspectives and experiences with healthcare providers' evaluation of behavior, communication, and QoL. The survey tool was developed by the study investigators in partnership with the LGS Foundation and had diffused to caregivers online by epilepsy advocacy groups including the Pediatric Epilepsy Surgery Alliance (PESA). Responses were analyzed. Descriptive statistics were calculated. The survey asked for caregiver perspectives and assessed which instruments the caregivers had previously been given for measuring these domains. RESULTS: Responses from 245 caregivers were included, with 132 (54%) caregivers of an individual with LGS and 113 (46%) caregivers of an individual with non-LGS related DRE. Respondents reported that 66% of their loved ones had undergone epilepsy-related surgery. Over 90% agreed that measuring behavior, communication, and QoL was important, but fewer than half felt that their healthcare providers evaluated these domains well. LGS caregivers largely shared non-LGS caregivers' perspectives; however, they reported more frequently that communication was not evaluated enough. Barriers to measuring these domains included a lack of good surveys (developmentally appropriate and specific to the type of epilepsy) or not receiving any survey instruments for these domains during clinic appointments. Caregivers play a crucial role for individuals with DRE, and their input is essential in identifying challenges and needs. Caregivers believe that measuring behavior, communication, and quality of life is important, and most of them feel that their loved ones are not adequately evaluated during their healthcare encounters. There is a need for appropriately scaled survey instruments to measure areas of importance for patients and caregivers, as well as incorporation of these outcomes in the healthcare discussion.

Quality of Life in Patients with High-grade Non-muscle-invasive Bladder Cancer Undergoing Standard Versus Reduced Frequency of Bacillus Calmette-Guérin Instillations: The EAU-RF NIMBUS Trial.

Background: Adverse events induced by intravesical bacillus Calmette-Guérin (BCG) to treat high-grade non-muscle-invasive bladder cancer (NMIBC) often lead to treatment discontinuation. The EAU-RF NIMBUS trial found a reduced number of standard-dose BCG instillations to be inferior with the standard regimen. Nonetheless, it remains important to evaluate whether patients in the reduced BCG treatment arm had better quality of life (QoL) due to a possible reduction in toxicity or burden. Objective: To evaluate whether patients in the EAU-RF NIMBUS trial experienced better QoL after a reduced BCG instillation frequency. Design setting and participants: A total of 359 patients from 51 European sites were randomized to one of two treatment arms between December 2013 and July 2019. The standard frequency arm (n = 182) was 6 weeks of BCG induction followed by 3 weeks of maintenance at months 3, 6, and 12. The reduced frequency arm (n = 177) was BCG induction at weeks 1, 2, and 6, followed by maintenance instillations at weeks 1 and 3 of months 3, 6, and 12. Outcome measurements and statistical analysis: Analyses were performed using an intention-to-treat analysis and a per-protocol analysis. QoL was measured using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 version 3.0 (QLQ-C30 v.03) prior to the first and last instillations of each BCG cycle. Group differences were determined using linear regression corrected for QoL at baseline. Differences in QoL over time were tested for significance using a linear mixed model. Side effects were recorded by the treating physician using a standardized form. Chi-square tests were used to compare the side-effect frequency between the arms. Results and limitations: There were no significant differences in the means of each QoL scale between the two arms. There were also no significant changes over time in all QoL domains for both arms. However, differences in the incidence of general malaise at T1 (before the last induction instillation), frequency, urgency, and dysuria at T7 (before the last maintenance instillation) were detected in favor of the reduced frequency arm. Conclusions: Reducing the BCG instillation frequency does not improve the QoL in NMIBC patients despite lower storage symptoms. Patient summary: In this study, we evaluated whether a reduction in the number of received bacillus Calmette-Guérin instillations led to better quality of life in patients with high-grade non-muscle-invasive bladder cancer. We found no difference in the quality of life between the standard and the reduced bacillus Calmette-Guérin instillation frequency. We conclude that reducing the number of instillations does not lead to better quality of life in patients with high-grade non-muscle-invasive bladder cancer.

Multidisciplinary Care for Pediatric Patients With Psychogenic Nonepileptic Seizures May Be Associated With Decreased Health Care Utilization.

Background and Objectives: Psychogenic nonepileptic seizures (PNES) are paroxysmal events that resemble epileptic seizures but have psychological underpinnings. Patients with PNES have high health care utilization. We hypothesize that appropriate care would lead to decreases in utilization. The aim of this study was to measure the impact of a multidisciplinary PNES clinic in reducing health care utilization (HCU) in youth with PNES referred to the clinic. Methods: We reviewed the frequency of visits to the emergency department (ED), urgent care (UC), planned and unplanned hospitalizations, neurodiagnostic studies, and total charges associated with these encounters 12 months before and 12 months after initial referral to the clinic. Manual chart review of all patients referred from November 2017 to March 2020 was performed. Results: Two hundred and twelve unique patients were included in this retrospective study. Patient sex was identified as 71% female, 28% male, and 1% other, with an average age of 14 years at diagnosis. These patients visited the ED a total of 410 times before being seen in the PNES clinic, which decreased to 187 visits after (75% reduction). All measures of HCU decreased in the 12 months after the visit, and statistically significant differences were observed in all measures of HCU except for head MRIs, leading to an estimated potential cost savings of $7,978,447. Discussion: Patients with PNES were found to have decreased health care utilization in the 12 months after referral to the Nationwide Children's Hospital multidisciplinary clinic, including significant decreases in emergency services and unnecessary diagnostic testing, in the 12 months after the referral.

Counseling on the Need for Folic Acid in Adolescents With Epilepsy.

Background and Objectives: Folic acid is an important supplement to take for women with epilepsy on antiseizure medications (ASMs). Determination of baseline counseling given to women with epilepsy and the association with folic acid being recommended were evaluated. Factors surrounding the association were reviewed. Methods: An exploratory retrospective review of women with epilepsy seen at a large Midwestern pediatric institution was performed between January 2018 and January 2020. Results: Patients who received preconception counseling were more likely to be given a recommendation to take folic acid. Patients on more than 1 ASM were likely to receive counseling. Patient age and race were associated with having folic acid recommended. Discussion: Providing preconception counseling for women with epilepsy is associated with an increased recommendation and prescription of folic acid. Further evaluation into possible disparities to receiving a folic acid recommendation is needed.

Self-management education for children with epilepsy and their caregivers. A scoping review.

Self-management education programs have been highly successful in preparing people to manage medical conditions with recurring events. A detailed curriculum for epilepsy patients, and their caretakers, is lacking. Here we assess what is available for patients who have disorders with recurring events and offer an approach to developing a potential self-care curriculum for patients with seizures and their caregivers. Among the anticipated components are a baseline efficacy assessment and training tailored to increasing self-efficacy, medication compliance, and stress management. Those at risk of status epilepticus will also need guidance in preparing a personalized seizure action plan and training in how to decide when rescue medication is appropriate and how to administer the therapy. Peers, as well as professionals, could teach and provide support. To our knowledge, no such programs are currently available in English. We encourage their creation, dissemination, and widespread use.

Efficacy of cannabidiol in convulsive and nonconvulsive seizure types associated with treatment-resistant epilepsies in the Expanded Access Program.

The cannabidiol (CBD) Expanded Access Program (EAP), initiated in 2014, provided CBD (Epidiolex) to patients with treatment-resistant epilepsy (TRE). In the final pooled analysis of 892 patients treated through January 2019 (median exposure = 694 days), CBD treatment was associated with a 46%-66% reduction in median monthly total (convulsive plus nonconvulsive) seizure frequency. CBD was well tolerated, and adverse events were consistent with previous findings. We used pooled EAP data to investigate the effectiveness of add-on CBD therapy for individual convulsive seizure types (clonic, tonic, tonic-clonic, atonic, focal to bilateral tonic-clonic), nonconvulsive seizure types (focal with and without impaired consciousness, absence [typical and atypical], myoclonic, myoclonic absence), and epileptic spasms. CBD treatment was associated with a reduction in the frequency of convulsive seizure types (median percentage reduction = 47%-100%), and nonconvulsive seizure types and epileptic spasms (median percentage reduction = 50%-100%) across visit intervals through 144 weeks of treatment. Approximately 50% of patients had ≥50% reduction in convulsive and nonconvulsive seizure types and epileptic spasms at nearly all intervals. These results show a favorable effect of long-term CBD use in patients with TRE, who may experience various convulsive and nonconvulsive seizure types. Future controlled trials are needed to confirm these findings.

Predictors of objective treatment adherence in adolescents with epilepsy: The important role of motivation.

OBJECTIVE: Adolescents with epilepsy are at heightened risk for suboptimal anti-seizure medication (ASM) adherence; however, there is a paucity of adherence interventions for this age group. The current study aimed to identify a comprehensive and novel set of predictors of objective, electronically-monitored ASM adherence in adolescents with epilepsy. METHODS: Participants included 104 adolescents (13-17 years old; M = 15.36 ± 1.40), diagnosed with epilepsy and their caregivers. Cross-sectional data were collected from adolescents, caregivers, healthcare providers, and medical chart reviews, including demographics (i.e., age, race/ethnicity, sex, insurance status), the COVID-19 pandemic (i.e., participation before versus during), seizure characteristics (i.e., presence and severity), ASM side effects (Pediatric Epilepsy Side Effects Questionnaire), adherence motivation (1-item 6-point Likert scale item), and adherence barriers (Pediatric Epilepsy Medication Self-Management Questionnaire). Electronically-monitored adherence data was collected via the AdhereTechTM pill bottle or the Vaica SimpleMedTM pillbox over 30 days. RESULTS: Adolescents demonstrated suboptimal adherence at 78 ± 31.6%, despite high ASM adherence motivation (M = 4.43 ± .94) and minimal adherence barriers (M = 35.64 ± 3.78). Hierarchical multiple regression, which included non-modifiable sociodemographic and medical variables (Block 1) and behaviorally modifiable psychosocial variables (Block 2) was significant, F(12,87) = 3.69, p < .001. Specifically, having private insurance (versus Medicaid or public insurance; t = -2.11, p = .038) and higher adherence motivation (t = 2.91, p = .005) predicted higher objective ASM adherence. CONCLUSION: Routine assessment of adherence predictors is vital for the promotion of adherence among adolescents with epilepsy. Adolescent adherence motivation may be an important element of multi-component interventions focused on improving ASM adherence in adolescents with epilepsy.

Implementing Evidence-Based, Electronic, Substance-Use Screening in a Primary Care Clinic.

PURPOSE: Substance use is common among adolescents, and among those with substance use disorders; use often persists into middle age, underlying the importance of early detection and treatment. The goal of this quality improvement project was to increase the electronic substance use screening rate of adolescents presenting for preventative health visits from 0% to 50% between March 2021 and September 2021. METHODS: This is an ongoing quality improvement project. Participants included patients ≥12 who presented to the Adolescent Medicine Clinic for preventative health visits. We incorporated the Screening to Brief Intervention into the existing Car, Relax, Alone, Forget, Friends, Trouble tool within the electronic health record. We completed a Plan-Do-Study-Act cycle by reviewing every patient's chart who did not receive screening and identified that a common reason for missed screening was designating the visit as "establishing care" rather than preventative health visit. We modified our eligible patient criteria to include all adolescents presenting to establish primary care. RESULTS: We achieved a statistically significant center-line shift with a p value (<.001) from approximately 0% at baseline to a new baseline of 85% from June 2021 to June 2022. After broadening our eligibility criteria, our electronic screening rate improved from 78% in November 2021, to 83% in December 2021. DISCUSSION: Electronic health record integration of the Screening to Brief Intervention/Car, Relax, Alone, Forget, Friends, Trouble is an effective method to systematically and electronically screen adolescents for SUD at preventative health visits. Integration using similar approaches may benefit other institutions interested in providing standardized SUD screening.

Pilot randomized controlled clinical trial of an adherence social norms intervention for adolescents with epilepsy.

OBJECTIVE: Non-adherence to anti-seizure medications (ASMs) is common for adolescents with epilepsy, with potentially devastating consequences. Existing adherence interventions in epilepsy do not meet the unique challenges faced by adolescents. Leveraging social norms capitalizes on the increased importance of peer influence while simultaneously targeting the low motivation levels of many adolescents. The current study examined the feasibility, acceptability, and satisfaction of a social norms adherence intervention in adolescents with epilepsy. METHODS: A pilot RCT of a mHealth social norms intervention was conducted with adolescents with epilepsy who demonstrated non-adherence (≤95% adherence) during baseline. Adolescents were randomized to either (1) mHealth social norms (reminders, individualized and social norms adherence feedback) or (2) control (reminders and individualized adherence feedback). Primary outcomes included feasibility, acceptability, and satisfaction. Exploratory outcomes included electronically monitored adherence, seizure severity, and health-related quality of life (HRQOL). RESULTS: One hundred four adolescents were recruited (53% female; Mage = 15.4 ± 1.4 years; 81% White: Non-Hispanic; 5% Black, 10% Bi/Multiracial; 2% White: Hispanic; 1% Other: Hispanic; 1% Bi/Multiracial-Hispanic). Forty-five percent screen-failed due to high adherence, 16% withdrew, and 38% were randomized to treatment (n = 19) or control (n = 21). Recruitment (75%), retention (78%), and treatment satisfaction were moderately high. Engagement with the intervention was moderate, with 64% of participants engaging with intervention notifications. Exploratory analyses revealed that after controlling for COVID-19 impact, the social norms intervention group maintained higher adherence over time compared to the control group. Small to moderate effect sizes were noted for seizure severity and HRQOL between groups. CONCLUSION: This pilot intervention appeared feasible and acceptable. Increases in adherence in the treatment versus control group were modest, but a future larger more adequately powered study is needed to detect effects. Notably, it appeared the COVID pandemic influenced adherence behaviors during our trial.

Long-term efficacy and safety of cannabidiol in patients with treatment-resistant epilepsies: Four-year results from the expanded access program.

OBJECTIVE: Cannabidiol (CBD) expanded access program, initiated in 2014, provided add-on CBD to patients with treatment-resistant epilepsies (TREs) at 35 US epilepsy centers. Prior publications reported results through December 2016; herein, we present efficacy and safety results through January 2019. METHODS: Patients received plant-derived highly purified CBD (Epidiolex®; 100 mg/ml oral solution), increasing from 2 to 10 mg/kg/day to tolerance or maximum 25-50 mg/kg/day dose, depending on the study site. Efficacy endpoints included percentage change from baseline in median monthly convulsive and total seizure frequency and ≥50%, ≥75%, and 100% responder rates across 12-week visit windows for up to 192 weeks. Adverse events (AEs) were documented at each visit. RESULTS: Of 892 patients in the safety analysis set, 322 (36%) withdrew; lack of efficacy (19%) and AEs (7%) were the most commonly reported primary reasons for withdrawal. Median (range) age was 11.8 years (range = 0-74.5), and patients were taking a median of three (range = 0-10) antiseizure medications (ASMs) at baseline; the most common ASMs were clobazam (47%), levetiracetam (34%), and valproate (28%). Median top CBD dose was 25 mg/kg/day; median exposure duration was 694 days. Median percentage reduction from baseline ranged 50%-67% for convulsive seizures and 46%-66% for total seizures. Convulsive seizure responder rates (≥50%, ≥75%, and 100% reduction) ranged 51%-59%, 33%-42%, and 11%-17% of patients across visit windows, respectively. AEs were reported in 88% of patients and serious AEs in 41%; 8% withdrew because of an AE. There were 20 deaths during the study deemed unrelated to treatment by the investigator. The most common AEs (≥20% of patients) were diarrhea (33%), seizure (24%), and somnolence (23%). SIGNIFICANCE: Add-on CBD was associated with sustained seizure reduction up to 192 weeks with an acceptable safety profile and can be used for long-term treatment of TREs.

Development of a core outcome set for quality of life for adults with drug-resistant epilepsy: A multistakeholder Delphi consensus study.

OBJECTIVE: In 2017, the American Academy of Neurology (AAN) convened the AAN Quality Measurement Set working group to define the improvement and maintenance of quality of life (QOL) as a key outcome measure in epilepsy clinical practice. A core outcome set (COS), defined as an accepted, standardized set of outcomes that should be minimally measured and reported in an area of health care research and practice, has not previously been defined for QOL in adult epilepsy. METHODS: A cross-sectional Delphi consensus study was employed to attain consensus from patients and caregivers on the QOL outcomes that should be minimally measured and reported in epilepsy clinical practice. Candidate items were compiled from QOL scales recommended by the AAN 2017 Quality Measurement Set. Inclusion criteria to participate in the Delphi study were adults with drug-resistant epilepsy diagnosed by a physician, no prior diagnosis of psychogenic nonepileptic seizures or a cognitive and/or developmental disability, or caregivers of patients meeting these criteria. RESULTS: A total of 109 people satisfied inclusion/exclusion criteria and took part in Delphi Round 1 (patients, n = 95, 87.2%; caregivers, n = 14, 12.8%), and 55 people from Round 1 completed Round 2 (patients, n = 43, 78.2%; caregivers, n = 12, 21.8%). One hundred three people took part in the final consensus round. Consensus was attained by patients/caregivers on a set of 36 outcomes that should minimally be included in the QOL COS. Of these, 32 of the 36 outcomes (88.8%) pertained to areas outside of seizure frequency and severity. SIGNIFICANCE: Using patient-centered Delphi methodology, this study defines the first COS for QOL measurement in clinical practice for adults with drug-resistant epilepsy. This set highlights the diversity of factors beyond seizure frequency and severity that impact QOL in epilepsy.

Proximal ventricular shunt catheter occlusion model.

PURPOSE: Proximal ventricular shunt catheter occlusion remains a problematic cause of shunt malfunction, and there is no consistent in vivo or in vitro model to help clinicians and researchers study this phenomenon. METHODS: An in vitro model utilizing standard proximal ventricular catheter and biological occluding agents mimicking choroid plexus was designed, constructed, and calibrated to occlude consistently within a specified timeframe. Hydrostatic pressure differential of 100 cmH2O was used as a driving force to generate flow through the catheter. Chalaza and vitelline membranes were harvested from avian eggs and used as occluding agents. Successful occlusion was defined as a greater than 90% reduction in volumetric flow rate through distal outlet. Histological sections of occluded catheters were performed and interpreted by a neuropathologist. RESULTS: Initial trials demonstrated successful standard catheter occlusion within 24 h using chalaza, vitelline membrane, and combination treatments. Repeat trials demonstrated consistency in successful occlusion within 5 min utilizing only vitelline membrane treatment. Histopathology demonstrated the vitelline membrane to consist of a thin, superficial layer of extraembryonic ectoderm; the chalaza was observed to consist of strands of mucin protein. CONCLUSIONS: An in vitro model of proximal ventricular shunt catheter occlusion was developed and calibrated for successful occlusion within 5 min. Future studies may utilize this model to rapidly test occlusion-resistant shunt designs and de-obstruction techniques.

A new flow cytometry assay identifies recipient IgG subtype antibodies binding donor cells: increasing donor availability for highly sensitised patients.

Objectives: There are four immunoglobulin (IgG) subtypes that have varying complement-activating ability: strong (IgG3 and IgG1) and weak (IgG2 and IgG4). The standard flow cytometric crossmatch (FCM) assay does not distinguish between the various subtypes of the IgG molecule. This study outlines the development and use of a novel cell-based IgG subtype-specific FCM assay that is able to detect the presence of and quantitate the IgG subtypes bound to donor cells. Methods: A six-colour lyophilised reagent was designed that specifically detects the four IgG subtypes, as well as distinguishes between T cells and B cells in the lymphocyte population. To test the efficacy of this reagent, a retrospective evaluation of a group of highly sensitised patients awaiting heart and kidney transplant was carried out, who, because of positive standard FCM results, had been deemed incompatible with numerous prior potential donors. Results: Observations in this study demonstrate that the positive standard FCM results were mainly because of the presence of noncomplement-activating IgG2 or IgG4 antibodies. The results were supported by the absence of C3d-binding donor-specific antibodies (DSA) and a negative complement-dependent cytotoxicity crossmatch (CDC). Conclusion: Preliminary data presented in this study demonstrate the reliability of the novel IgG subtype assay to detect the presence of pretransplant, complement-activating antibodies bound to donor cells. The knowledge gained from the IgG subtype assay and the C3d-binding specificities of DSAs provides improved identification of donor suitability in pretransplant patients, potentially increasing the number of transplants.