UK research priority setting for childhood neurological conditions.

AIM: To identify research priorities regarding the effectiveness of interventions for children and young people (CYP) with childhood neurological conditions (CNCs). These include common conditions such as epilepsies and cerebral palsy, as well as many rare conditions. METHOD: The National Institute for Health and Care Research (NIHR) and the James Lind Alliance (JLA) champion and facilitate priority setting partnerships (PSPs) between patients, caregivers, and clinicians (stakeholders) to identify the most important unanswered questions for research (uncertainties). A NIHR-JLA and British Paediatric Neurology Association collaboration used the JLA PSP methodology. This consisted of two surveys to stakeholders: survey 1 (to identify uncertainties) and survey 2 (a prioritization survey). The final top 10 priorities were agreed by consensus in a stakeholder workshop. RESULTS: One hundred and thirty-two charities and partner organizations were invited to participate. In survey 1, 701 participants (70% non-clinicians, including CYP and parent and caregivers) submitted 1800 uncertainties from which 44 uncertainties were identified for prioritization in survey 2; from these, 1451 participants (83% non-clinicians) selected their top 10 priorities. An unweighted amalgamated score across participant roles was used to select 26. In the final workshop, 14 health care professionals, 11 parent and caregivers, and two CYP ranked the 26 questions to finalize the top 10 priorities. Ten top priority questions were identified regarding interventions to treat CYP with CNCs and their associated comorbidities, for example, sleep, emotional well-being, and distressing symptoms. INTERPRETATION: The results of this study will inform research into the effectiveness of interventions for children with neurological conditions.

Comparison of neurodevelopmental, educational and adult socioeconomic outcomes in offspring of women with and without epilepsy: A systematic review and meta-analysis.

BACKGROUND: Adequate pre-pregnancy counselling and education planning are essential to improve outcomes for offspring of women with epilepsy (OWWE). The current systematic review and meta-analysis aimed to compare outcomes for OWWE and offspring of women without epilepsy (OWWoE). METHODS: We conducted a systematic review and meta-analysis. We searched MEDLINE, EMBASE, CINAHL, PsycINFO (database inception-1st January 2023), OpenGrey, GoogleScholar, and hand-searched journals and reference lists of included studies to identify eligible studies. We placed no language restrictions and included observational studies concerning OWWE and OWWoE. We followed the PRIMSA checklist for abstracting data. The Newcastle-Ottawa Scale for risk of bias assessment was conducted independently by two authors with mediation by a third. We report pooled unadjusted odds ratios (OR) or mean differences (MD) with 95% confidence intervals (95CI) from random (I2>50%) or fixed (I2<50%) effects meta-analyses. Outcomes of interest included offspring autism, attention deficit/hyperactive disorder, intellectual disability, epilepsy, developmental disorder, intelligence, educational, and adulthood socioeconomic outcomes. RESULTS: Of 10,928 articles identified, we included 21 in meta-analyses. OWWE had increased odds of autism (2 articles, 4,502,098 offspring) OR [95CI] 1·67 [1·54, 1·82], attention-deficit/hyperactivity disorder (3 articles, 957,581 offspring) 1·59 [1·44, 1·76], intellectual disability (2 articles, 4,501,786 children) 2·37 [2·13, 2·65], having special educational needs (3 articles, 1,308,919 children) 2·60 [1·07, 6·34]. OWWE had worse mean scores for full-scale intelligence (5 articles, 989 children) -6·05 [-10·31, -1·79]. No studies were identified that investigated adulthood socioeconomic outcomes. CONCLUSIONS: Increased odds of poor outcomes are higher with greater anti-seizure medication burden including neurodevelopmental and educational outcomes. In fact, these two outcomes seem to be worse in OWWE compared to OWWoE, even if there was no ASM exposure during pregnancy, but further work is needed to take into account potential confounding factors.

Socioeconomic status in adulthood of children with and without a history of seizures: A retrospective cohort study.

OBJECTIVE: Compare adulthood socioeconomic status for children with and without a history of seizures. METHODS: Retrospective cohort study using Aberdeen Children of the Nineteen Fifties (ACONF) data comprising children born 1950-1956 attending primary school 1962-1964, with follow-up data collected in 2001. Adulthood socioeconomic status was based on registrar general measure of occupational social class and categorised as high or low. We adjusted for potentially confounding variables including childhood socioeconomic status, behavioural issues (Rutter A/B scores), biological sex, school test scores, educational attainment, parental engagement with education, peer-status in school, and alcohol use in adulthood. A multivariate binary logistic regression was performed to estimate the adjusted association between children with a history of seizures of any type (for example febrile seizures, or provoked seizures of any other etiology or seizures in the context of epilepsy) or severity and adult socioeconomic status. Multiple imputation using the Monte-Carlo-Markov-Chain method accounted for missing data. RESULTS: Pooled estimates (N = 2,208) comparing children with a history of seizures (n = 81) and children without a history of seizures (n = 2,127) found no differences between these cohorts in terms of adulthood socioeconomic status in both unadjusted (Odds Ratio (OR) 1.45 [95 % CI 0.71-2.96], p = 0.31) and adjusted (1.02 [0.46, 2.24], p = 0.96) analyses. Compared to males, females were at increased odds of having a lower socioeconomic status in adulthood (1.56 [1.13-2.17], p = 0.01).Compared to those with low educational attainment, those with moderate (0.32 [0.21, 0.48], p < 0.001) and high (0.12 [0.07, 0.20], p < 0.001) educational attainment were at reduced odds of having a lower socioeconomic status in adulthood. CONCLUSION: Cognitive problems in childhood (using educational attainment and scores on primary school tests proxy markers for cognition) rather than a history of seizures per se, were associated with lower SES in a population of adults born 1950-56 in Aberdeen. This relationship may be different depending on the time in history and nation/region of study. Given the changes in health, education and social support in the management of children with seizures over time, it would be of interest to investigate outcomes in a contemporary cohort. Such studies should ideally have validated diagnoses of seizures, details on seizure characteristics such as seizure type and severity, and a large sample size using national data.

Health care utilization and mortality for people with epilepsy during COVID-19: A population study.

OBJECTIVE: This study was undertaken to characterize changes in health care utilization and mortality for people with epilepsy (PWE) during the COVID-19 pandemic. METHODS: We performed a retrospective study using linked, individual-level, population-scale anonymized health data from the Secure Anonymised Information Linkage databank. We identified PWE living in Wales during the study "pandemic period" (January 1, 2020-June 30, 2021) and during a "prepandemic" period (January 1, 2016-December 31, 2019). We compared prepandemic health care utilization, status epilepticus, and mortality rates with corresponding pandemic rates for PWE and people without epilepsy (PWOE). We performed subgroup analyses on children (<18 years old), older people (>65 years old), those with intellectual disability, and those living in the most deprived areas. We used Poisson models to calculate adjusted rate ratios (RRs). RESULTS: We identified 27 279 PWE who had significantly higher rates of hospital (50.3 visits/1000 patient months), emergency department (55.7), and outpatient attendance (172.4) when compared to PWOE (corresponding figures: 25.7, 25.2, and 87.0) in the prepandemic period. Hospital and epilepsy-related hospital admissions, and emergency department and outpatient attendances all reduced significantly for PWE (and all subgroups) during the pandemic period. RRs [95% confidence intervals (CIs)] for pandemic versus prepandemic periods were .70 [.69-.72], .77 [.73-.81], .78 [.77-.79], and .80 [.79-.81]. The corresponding rates also reduced for PWOE. New epilepsy diagnosis rates decreased during the pandemic compared with the prepandemic period (2.3/100 000/month cf. 3.1/100 000/month, RR = .73, 95% CI = .68-.78). Both all-cause deaths and deaths with epilepsy recorded on the death certificate increased for PWE during the pandemic (RR = 1.07, 95% CI = .997-1.145 and RR = 2.44, 95% CI = 2.12-2.81). When removing COVID deaths, RRs were .88 (95% CI = .81-.95) and 1.29 (95% CI = 1.08-1.53). Status epilepticus rates did not change significantly during the pandemic (RR = .95, 95% CI = .78-1.15). SIGNIFICANCE: All-cause non-COVID deaths did not increase but non-COVID deaths associated with epilepsy did increase for PWE during the COVID-19 pandemic. The longer term effects of the decrease in new epilepsy diagnoses and health care utilization and increase in deaths associated with epilepsy need further research.

Epilepsy and the risk of COVID-19-related hospitalization and death: A population study.

OBJECTIVE: People with epilepsy (PWE) may be at an increased risk of severe COVID-19. It is important to characterize this risk to inform PWE and for future health and care planning. We assessed whether PWE were at higher risk of being hospitalized with, or dying from, COVID-19. METHODS: We performed a retrospective cohort study using linked, population-scale, anonymized electronic health records from the SAIL (Secure Anonymised Information Linkage) databank. This includes hospital admission and demographic data for the complete Welsh population (3.1 million) and primary care records for 86% of the population. We identified 27 279 PWE living in Wales during the study period (March 1, 2020 to June 30, 2021). Controls were identified using exact 5:1 matching (sex, age, and socioeconomic status). We defined COVID-19 deaths as having International Classification of Diseases, 10th Revision (ICD-10) codes for COVID-19 on death certificates or occurring within 28 days of a positive SARS-CoV-2 polymerase chain reaction (PCR) test. COVID-19 hospitalizations were defined as having a COVID-19 ICD-10 code for the reason for admission or occurring within 28 days of a positive SARS-CoV-2 PCR test. We recorded COVID-19 vaccinations and comorbidities known to increase the risk of COVID-19 hospitalization and death. We used Cox proportional hazard models to calculate hazard ratios. RESULTS: There were 158 (.58%) COVID-19 deaths and 933 (3.4%) COVID-19 hospitalizations in PWE, and 370 (.27%) deaths and 1871 (1.4%) hospitalizations in controls. Hazard ratios for COVID-19 death and hospitalization in PWE compared to controls were 2.15 (95% confidence interval [CI] = 1.78-2.59) and 2.15 (95% CI = 1.94-2.37), respectively. Adjusted hazard ratios (adjusted for comorbidities) for death and hospitalization were 1.32 (95% CI = 1.08-1.62) and 1.60 (95% CI = 1.44-1.78). SIGNIFICANCE: PWE are at increased risk of being hospitalized with, and dying from, COVID-19 when compared to age-, sex-, and deprivation-matched controls, even when adjusting for comorbidities. This may have implications for prioritizing future COVID-19 treatments and vaccinations for PWE.

A case-control study to investigate the prevalence of obstructive sleep apnea and the utility of the Sleep-Related Breathing Disorder scale of the Pediatric Sleep Questionnaire in children and young people with epilepsy.

STUDY OBJECTIVES: Epilepsy and obstructive sleep apnea syndrome (OSAS) are each relatively common in children. OSAS may affect cognition, such that recognition of OSAS is important for children and young people with epilepsy (CYPWE). Published pilot data reported 55% of CYPWE had symptoms suggestive of OSAS, compared with 7% of typically developing controls. The primary aim of this study was to ascertain OSAS prevalence by polysomnography in CYPWE, with secondary aims being to evaluate the utility of sleep questionnaires in CYPWE. METHODS: CYPWE and age- and sex-matched typically developing controls were studied. A single night of level I attended polysomnography was undertaken, along with questionnaires (Sleep-Related Breathing Disorder scale of the Pediatric Sleep Questionnaire, Pittsburgh Sleep Quality Index, and the childhood and adolescent Epworth Sleepiness Scale). OSAS was defined as obstructive apnea-hypopnea index of ≥ 1 event/h. RESULTS: Polysomnography was performed in 72 children including 48 CYPWE (60% male) and 24 controls (54% male). Mean age (11 years) was similar for CYPWE and controls (P = .42), with slightly higher body mass index z scores (0.7 vs 0.1, P = .03) noted in CYPWE. Mean obstructive apnea-hypopnea index was 0.61 in CYPWE vs 0.42 in controls (P = .62). Despite higher Sleep-Related Breathing Disorder scale of the Pediatric Sleep Questionnaire scores in CYPWE (0.38 vs 0.12, P < .001), no difference in OSAS prevalence (10% vs 4%, P = .78) was found. CYPWE had higher childhood and adolescent Epworth Sleepiness Scale (6 vs 3.5, P = .01) and Pittsburgh Sleep Quality Index (5 vs 3.3, P = .02) scores, indicating greater levels of daytime sleepiness and poorer sleep quality. CONCLUSIONS: The study found no evidence for increased OSAS prevalence in CYPWE, and the utility of the Sleep-Related Breathing Disorder scale of the Pediatric Sleep Questionnaire in predicting OSAS appears limited for CYPWE. CYPWE are, however, demonstrably sleepier and have poorer sleep quality. The cause for these findings remains unclear. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Investigation of Sleep Quality and Prevalence of Sleep-disordered Breathing in Children and Young People With Epilepsy; URL: https://www.clinicaltrials.gov/study/NCT03103841; Identifier: NCT03103841. CITATION: Urquhart DS, McLellan AE, Hill LE, et al. A case-control study to investigate the prevalence of obstructive sleep apnea and the utility of the Sleep-Related Breathing Disorder scale of the Pediatric Sleep Questionnaire in children and young people with epilepsy. J Clin Sleep Med. 2024;20(7):1039-1047.

Evaluating fenfluramine hydrochloride as an oral solution for the treatment of seizures associated with Lennox-Gastaut syndrome.

INTRODUCTION: Lennox-Gastaut syndrome (LGS) is a severe childhood-onset developmental and epileptic encephalopathy characterized by treatment-refractory seizures, including tonic/atonic 'drop' seizures, and intellectual impairment and slow spike-wave discharges on the electroencephalogram. Fenfluramine, previously prescribed as a weight-loss drug but then withdrawn, has recently been approved in the US, EU, and UK for the adjunct treatment of seizures associated with LGS. AREAS COVERED: The authors review the efficacy and safety findings from clinical trials of fenfluramine in LGS. The authors then discuss the evidence for adverse effects that may be of particular concern to fenfluramine, namely cardiac abnormalities, and weight loss, in the context of the use of fenfluramine for the treatment of the refractory seizures in LGS. EXPERT OPINION: Fenfluramine has demonstrated efficacy in reducing the frequency of seizures in LGS, notably drop seizures, in short-term and long-term clinical trials. Valvular heart disease and pulmonary hypertension have not been reported at the low doses (≤26 mg/day) used in these studies, however, data are limited. Due to its novel mechanism of action, fenfluramine may be of benefit in LGS which has not responded adequately to other antiseizure medications. However, none of these medications, including fenfluramine, achieves the ultimate goal of seizure freedom in most cases.

Critical success index or F measure to validate the accuracy of administrative healthcare data identifying epilepsy in deceased adults in Scotland.

BACKGROUND: Methods to undertake diagnostic accuracy studies of administrative epilepsy data are challenged by lack of a way to reliably rank case-ascertainment algorithms in order of their accuracy. This is because it is difficult to know how to prioritise positive predictive value (PPV) and sensitivity (Sens). Large numbers of true negative (TN) instances frequently found in epilepsy studies make it difficult to discriminate algorithm accuracy on the basis of negative predictive value (NPV) and specificity (Spec) as these become inflated (usually >90%). This study demonstrates the complementary value of using weather forecasting or machine learning metrics critical success index (CSI) or F measure, respectively, as unitary metrics combining PPV and sensitivity. We reanalyse data published in a diagnostic accuracy study of administrative epilepsy mortality data in Scotland. METHOD: CSI was calculated as 1/[(1/PPV) + (1/Sens) - 1]. F measure was calculated as 2.PPV.Sens/(PPV + Sens). CSI and F values range from 0 to 1, interpreted as 0 = inaccurate prediction and 1 = perfect accuracy. The published algorithms were reanalysed using these and their accuracy re-ranked according to CSI in order to allow comparison to the original rankings. RESULTS: CSI scores were conservative (range 0.02-0.826), always less than or equal to the lower of the corresponding PPV (range 39-100%) and sensitivity (range 2-93%). F values were less conservative (range 0.039-0.905), sometimes higher than either PPV or sensitivity, but were always higher than CSI. Low CSI and F values occurred when there was a large difference between PPV and sensitivity, e.g. CSI was 0.02 and F was 0.039 in an instance when PPV was 100% and sensitivity was 2%. Algorithms with both high PPV and sensitivity performed best in terms of CSI and F measure, e.g. CSI was 0.826 and F was 0.905 in an instance when PPV was 90% and sensitivity was 91%. CONCLUSION: CSI or F measure can combine PPV and sensitivity values into a convenient single metric that is easier to interpret and rank in terms of diagnostic accuracy than trying to rank diagnostic accuracy according to the two measures themselves. CSI or F prioritise instances where both PPV and sensitivity are high over instances where there are large differences between PPV and sensitivity (even if one of these is very high), allowing diagnostic accuracy thresholds based on combined PPV and sensitivity to be determined. Therefore, CSI or F measures may be helpful complementary metrics to report alongside PPV and sensitivity in diagnostic accuracy studies of administrative epilepsy data.

Efficient organisation of the contralateral hemisphere connectome is associated with improvement in intelligence quotient after paediatric epilepsy surgery.

OBJECTIVE: Aims of epilepsy surgery in childhood include optimising seizure control and facilitating cognitive development. Predicting which children will improve cognitively is challenging. We investigated the association of the pre-operative structural connectome of the contralateral non-operated hemisphere with improvement in intelligence quotient (IQ) post-operatively. METHODS: Consecutive children who had undergone unilateral resective procedures for epilepsy at a single centre were retrospectively identified. We included those with pre-operative volume T1-weighted non-contrast brain magnetic resonance imaging (MRI), no visible contralateral MRI abnormalities, and both pre-operative and two years post-operative IQ assessment. The MRI of the hemisphere contralateral to the side of resection was anatomically parcellated into 34 cortical regions and the covariance of cortical thickness between regions was used to create binary and weighted group connectomes. RESULTS: Eleven patients with a post-operative IQ increase of at least 10 points at two years were compared with twenty-four patients with no change in IQ score. Children who gained at least 10 IQ points post-operatively had a more efficiently structured contralateral hemisphere connectome with higher global efficiency (0.74) compared to those whose IQ did not change at two years (0.58, p = 0.014). This was consistent across thresholds and both binary and weighted networks. There were no statistically significant group differences in age, sex, age at onset of epilepsy, pre-operative IQ, mean cortical thickness, side or site of procedure, two year post-operative Engel scores or use of anti-seizure medications between the two groups. CONCLUSIONS: Surgical procedures to reduce or stop seizures may allow children with an efficiently structured contralateral hemisphere to achieve their cognitive potential.

The association of structural connectome efficiency with cognition in children with epilepsy.

OBJECTIVE: Cognitive impairment is common in children with epilepsy (CWE), but understanding the underlying pathological processes is challenging. We aimed to investigate the association of structural brain network organisation with cognition. METHODS: This was a retrospective cohort study of CWE without structural brain abnormalities, comparing whole brain network characteristics between those with cognitive impairment and those with intact cognition. We created structural whole-brain connectomes from anatomical and diffusion tensor magnetic resonance imaging using the number of streamlines and tract-averaged fractional anisotropy. We assessed the differences in average path length and global network efficiency between children with cognitive impairment and those without,using multivariable analyses to account for possible clinical group differences. RESULTS: Twenty-eight CWE and cognitive impairment had lower whole brain network global efficiency compared with 34 children with intact cognition (0.54, standard deviation (SD):0.003 vs. 0.56, SD:0.002, p < 0.001), which is equivalent to longer normalized network average path lengths (1.14, SD:0.05 vs. 1.10, SD:0.02, p = 0.003). In multivariable logistic regression cognitive impairment was not significantly associated with age of onset, duration of epilepsy, or number of antiseizure medications, but was independently associated with daily seizures (p = 0.04) and normalized average path length (p = 0.007). CONCLUSIONS: Higher structural network average path length and lower global network efficiency may be imaging biomarkers of cognitive impairment in epilepsy. Understanding what leads to changes in structural connectivity could aid identification of modifiable risk factors for cognitive impairment. These findings are only applicable to the specific cohort studied, and further confirmation in other cohorts is required.

Epilepsy-related mortality during the COVID-19 pandemic: A nationwide study of routine Scottish data.

OBJECTIVE: To examine whether epilepsy-related deaths increased during the COVID-19 pandemic and if the proportion with COVID-19 listed as the underlying cause is different between people experiencing epilepsy-related deaths and those experiencing deaths unrelated to epilepsy. METHODS: This was a Scotland-wide, population-based, cross-sectional study of routinely-collected mortality data pertaining to March-August of 2020 (COVID-19 pandemic peak) compared to the corresponding periods in 2015-2019. ICD-10-coded causes of death of deceased people of any age were obtained from a national mortality registry of death certificates in order to identify those experiencing epilepsy-related deaths (coded G40-41), deaths with COVID-19 listed as a cause (coded U07.1-07.2), and deaths unrelated to epilepsy (death without G40-41 coded). The number of epilepsy-related deaths in 2020 were compared to the mean observed through 2015-2019 on an autoregressive integrated moving average (ARIMA) model (overall, men, women). Proportionate mortality and odds ratios (OR) for deaths with COVID-19 listed as the underlying cause were determined for the epilepsy-related deaths compared to deaths unrelated to epilepsy, reporting 95% confidence intervals (CIs). RESULTS: A mean number of 164 epilepsy-related deaths occurred through March-August of 2015-2019 (of which a mean of 71 were in women and 93 in men). There were subsequently 189 epilepsy-related deaths during the pandemic March-August 2020 (89 women, 100 men). This was 25 more epilepsy-related deaths (18 women, 7 men) compared to the mean through 2015-2019. The increase in women was beyond the mean year-to-year variation seen in 2015-2019. Proportionate mortality with COVID-19 listed as the underlying cause was similar between people experiencing epilepsy-related deaths (21/189, 11.1%, CI 7.0-16.5%) and deaths unrelated to epilepsy (3,879/27,428, 14.1%, CI 13.7-14.6%), OR 0.76 (CI 0.48-1.20). Ten of 18 excess epilepsy-related deaths in women had COVID-19 listed as an additional cause. CONCLUSIONS: There is little evidence to suggest there have been any major increases in epilepsy-related deaths in Scotland during the COVID-19 pandemic. COVID-19 is a common underlying cause of both epilepsy-related and unrelated deaths.

Mortality in children with epilepsy: Cohort study using the clinical practice research datalink.

OBJECTIVE: To estimate Mortality Rate (MR) in UK children with epilepsy (CWE) compared to children without epilepsy (CWOE), describe causes of death, determine Mortality Rate Ratios (MRRs) for cause-specific mortality, and to analyse the contribution of co-morbidities (respiratory disease, neoplasm, and congenital disorders) to mortality rate. METHOD: Retrospective cohort study of children born between 1998 and 2017, using linked data from the Clinical Practice Research Datalink Gold (Set 18). Epilepsy diagnoses were identified using previously validated codes. Causes of death were defined as natural or non-natural. Epilepsy-related deaths in CWE were those where underlying or contributing cause of death was epilepsy, status epilepticus, seizures, ill-defined/unknown cause or sudden death. We used Cox proportional hazard analysis to investigate associations of epilepsy and mortality. RESULTS: There were 1,191,304 children followed for 13,994,916 person-years (median: 12) if which 9665 (0.8%) had epilepsy. Amongst CWE, 3.4% died. MR of CWE was 4.1 (95%CI 3.7-4.6)/1,000 person-years. CWE had an increased adjusted all-cause mortality (MRR 50.9,95%CI 44.8-57.7) compared to CWOE. Amongst the 330 deaths in CWE, 323 (98%) were natural, 7 (2%) non-natural, 80 (24%) epilepsy-related. MRR of non-natural deaths was 2.09 (95%CI 0.92,4.74, p = 0.08). SIGNIFICANCE: Amongst CWE, 3.4% died during the study period. All-cause mortality rate in CWE was 4/1,000 person-years representing a fifty-fold increased mortality risk, after taking into account sex and socioeconomic status, compared to similarly aged children who did not have epilepsy. Causes of death mostly were not seizure-related. Non-natural death in CWE was uncommon.

Current and emerging pharmacotherapy for the treatment of Lennox-Gastaut syndrome.

INTRODUCTION: Lennox-Gastaut syndrome (LGS) is a severe childhood-onset epileptic encephalopathy, characterized by multiple seizure types, generalized slow spike-and-wave complexes in the EEG, and cognitive impairment. Seizures in LGS are typically resistant to treatment with antiseizure medications (ASMs). Tonic/atonic ('drop') seizures are of particular concern, due to their liability to cause physical injury. AREAS COVERED: We summarize evidence for current and emerging ASMs for the treatment of seizures in LGS. The review focuses on findings from randomized, double-blind, placebo-controlled trials (RDBCTs). For ASMs for which no double-blind trials were identified, lower quality evidence was considered. Novel pharmacological agents currently undergoing investigation for the treatment of LGS are also briefly discussed. EXPERT OPINION: Evidence from RDBCTs supports the use of cannabidiol, clobazam, felbamate, fenfluramine, lamotrigine, rufinamide, and topiramate as adjunct treatments for drop seizures. Percentage decreases in drop seizure frequency ranged from 68.3% with high-dose clobazam to 14.8% with topiramate. Valproate continues to be considered the first-line treatment, despite the absence of RDBCTs specifically in LGS. Most individuals with LGS will require treatment with multiple ASMs. Treatment decisions should be individualized and take into account adverse effects, comorbidities, general quality of life, and drug interactions, as well as individual efficacy.

Screening for anxiety, depression and suicidality by epilepsy specialists in adult services in Scotland.

OBJECTIVE: Clinical guidelines recommend screening people with epilepsy (PWE) regularly for mental distress, but it is unclear how guidelines are implemented. We surveyed epilepsy specialists in adult Scottish services to determine approaches used to screen for anxiety, depression, and suicidality; the perceived difficulty of screening; factors associated with intention to screen; and treatment decisions made following positive screens. METHODS: An anonymous email-based questionnaire survey of epilepsy nurses and epilepsy neurology specialists (n = 38) was conducted. RESULTS: Two in every three specialists used a systematic screening approach; a third did not. Clinical interview was employed more often than standardized questionnaire. Clinicians reported positive attitudes towards screening but found screening difficult to implement. Intention to screen was associated with favorable attitude, perceived control, and social norm. Pharmacological and non-pharmacological interventions were proposed equally often for those screening positive for anxiety or depression. CONCLUSION: Routine screening for mental distress is carried out in Scottish epilepsy treatment settings but is not universal. Attention should be paid to clinician factors associated with screening, such as intention to screen and resulting treatment decisions. These factors are potentially modifiable, offering a means of closing the gap between guideline recommendations and clinical practice.

Comparison of Perinatal Outcomes for Women With and Without Epilepsy: A Systematic Review and Meta-analysis.

Importance: Pregnant women who have epilepsy need adequate engagement, information, and pregnancy planning and management to improve pregnancy outcomes. Objective: To investigate perinatal outcomes in women with epilepsy compared with women without epilepsy. Data Sources: Ovid MEDLINE, Embase, CINAHL, and PsycINFO were searched with no language or date restrictions (database inception through December 6, 2022). Searches also included OpenGrey and Google Scholar and manual searching in journals and reference lists of included studies. Study Selection: All observational studies comparing women with and without epilepsy were included. Data Extraction and Synthesis: The PRISMA checklist was used for abstracting data and the Newcastle-Ottawa Scale for risk-of-bias assessment. Data extraction and risk-of-bias assessment were done independently by 2 authors with mediation conducted independently by a third author. Pooled unadjusted odds ratios (OR) or mean differences were reported with 95% CI from random-effects (I2 heterogeneity statistic >50%) or fixed-effects (I2 < 50%) meta-analyses. Main Outcomes and Measures: Maternal, fetal, and neonatal complications. Results: Of 8313 articles identified, 76 were included in the meta-analyses. Women with epilepsy had increased odds of miscarriage (12 articles, 25 478 pregnancies; OR, 1.62; 95% CI, 1.15-2.29), stillbirth (20 articles, 28 134 229 pregnancies; OR, 1.37; 95% CI, 1.29-1.47), preterm birth (37 articles, 29 268 866 pregnancies; OR, 1.41; 95% CI, 1.32-1.51) and maternal death (4 articles, 23 288 083 pregnancies; OR, 5.00; 95% CI, 1.38-18.04). Neonates born to women with epilepsy had increased odds of congenital conditions (29 articles, 24 238 334 pregnancies; OR, 1.88; 95% CI, 1.66-2.12), neonatal intensive care unit admission (8 articles, 1 204 428 pregnancies; OR, 1.99; 95% CI, 1.58-2.51), and neonatal or infant death (13 articles, 1 426 692 pregnancies; OR, 1.87; 95% CI, 1.56-2.24). The increased odds of poor outcomes was increased with greater use of antiseizure medication. Conclusions and Relevance: This systematic review and meta-analysis found that women with epilepsy have worse perinatal outcomes compared with women without epilepsy. Women with epilepsy should receive pregnancy counseling from an epilepsy specialist who can also optimize their antiseizure medication regimen before and during pregnancy.

Questionnaire-based screening for mental distress in epilepsy: Outline and feasibility of an outpatient screening and intervention pathway.

OBJECTIVE: Mental distress is present in a significant proportion of people with epilepsy (PWE), with a negative impact across life domains. It is underdiagnosed and under-treated despite guidelines recommending screening for its presence (e.g., SIGN, 2015). We describe a tertiary-care epilepsy mental distress screening and treatment pathway, with a preliminary investigation of its feasibility. METHODS: We selected psychometric screening instruments for depression, anxiety, quality of life (QOL), and suicidality, establishing treatment options matched to instrument scores on the Patient Health Questionnaire 9 (PHQ-9), along 'traffic light' lines. We determined feasibility outcomes including recruitment and retention rates, resources required to run the pathway, and level of psychological need. We undertook a preliminary investigation of change in distress scores over a 9-month interval and determined PWE engagement and the perceived usefulness of pathway treatment options. RESULTS: Two-thirds of eligible PWE were included in the pathway with an 88% retention rate. At the initial screen, 45.8% of PWE required either an 'Amber-2' intervention (for moderate distress) or a 'Red' one (for severe distress). The equivalent figure at the 9-month re-screen was 36.8%, reflective of an improvement in depression and QOL scores. Online charity-delivered well-being sessions and neuropsychology were rated highly for engagement and perceived usefulness, but computerized cognitive behavioral therapy was not. The resources required to run the pathway were modest. CONCLUSION: Outpatient mental distress screening and intervention are feasible in PWE. The challenge is to optimize methods for screening in busy clinics and to determine the best (and most acceptable) interventions for screening positive PWE.

Functional neurological disorder in children and young people: Incidence, clinical features, and prognosis.

AIM: To report incidence, demographic and clinical characteristics, and symptom outcome of functional neurological disorder (FND) in children. METHOD: Children diagnosed with FND at a regional children's hospital were prospectively recruited by weekly active surveillance for 36 months. Demographic, clinical, and follow-up data were retrospectively extracted by review of electronic records. Descriptive statistical analyses were used. RESULTS: Ninety-seven children (age range 5-15 years) met the case definition of FND (annual incidence 18.3 per 100 000 children). Children with FND were likely to be female (n = 68 [70%]) and older (median 13 years) with no difference in the Scottish Index of Multiple Deprivation (marker of socioeconomic status) compared with the general childhood population. Functional motor (41%) and sensory (41%) symptoms were most common; other somatic symptoms such as headache (31%) and pain (27%) were frequent. Self-reported psychiatric symptoms and infection/inflammation were the most common predisposing and precipitating factors respectively. At a median of 15 months follow-up, 49% of 75 children reported improvement or resolution of FND symptoms with no prognostic factors found. INTERPRETATION: At this regional centre, FND in children had a higher incidence than previously reported and a less optimistic outcome than in some other studies.

Using Critical Success Index or Gilbert Skill Score as composite measures of positive predictive value and sensitivity in diagnostic accuracy studies: Weather forecasting informing epilepsy research.

The Critical Success Index (CSI) and Gilbert Skill score (GS) are verification measures that are commonly used to check the accuracy of weather forecasting. In this article, we propose that they can also be used to simplify the joint interpretation of positive predictive value (PPV) and sensitivity estimates across diagnostic accuracy studies of epilepsy data. This is because CSI and GS each provide a single measure that takes the weather forecasting equivalent of PPV and sensitivity into account. We have re-analysed data from our recent systematic review of diagnostic accuracy studies of administrative epilepsy data using CSI and GS. We summarise the results and benefits of this approach.