Vagus nerve stimulation in lesional and Non-Lesional Drug-Resistant focal onset epilepsies.

PURPOSE: Drug-resistant epilepsy (DRE) affects one-third of patients with focal epilepsy. A large portion of patients are not candidates for epilepsy surgery, thus alternative options, such as vagus nerve stimulation (VNS), are proposed. Our objective is to study the effect of vagus nerve stimulation on lesional versus non-lesional epilepsies. METHODS: This is a retrospective cohort study in a single center in London, Ontario, which includes patients with DRE implanted with VNS, implanted between 1997-2018 and the date of analysis is December 2023. PARTICIPANTS: Patients implanted with VNS were classified by lesional (VNS-L) and non-lesional (VNS-NL) based on their MRI head findings. We further subdivided the VNS groups into patients with VNS alone versus those who also had additional epilepsy surgeries. RESULTS: A total of 29 patients were enrolled in the VNS-L, compared to 29 in the VNS-NL. The median age of the patients in the study was 31.8 years, 29.31 % were men (N = 17). 41.4 % (n = 12) of the patients were VNS responders (≥50 % seizure reduction) in the VNS-L group compared to 62.0 % (n = 18) in the VNS-NL group (p = 0.03). When other epilepsy surgeries were combined with VNS in the VNS-L group, the median rate of seizure reduction was greater (72.4 (IQR 97.17-45.88) than the VNS-NL group 53.9 (IQR 92.22-27.92); p = 0.27). CONCLUSIONS: VNS is a therapeutic option for patients with lesional epilepsy, with slightly inferior results compared to patients with non-lesional epilepsy. Patients implanted with VNS showed higher seizure reduction rates if they had previous epilepsy surgeries. This study demonstrates that VNS in lesional epilepsies can be an effective treatment.

Evaluating the Current State of Epilepsy Care in the Province of Ontario.

There are numerous challenges pertaining to epilepsy care across Ontario, including Epilepsy Monitoring Unit (EMU) bed pressures, surgical access and community supports. We sampled the current clinical, community and operational state of Ontario epilepsy centres and community epilepsy agencies post COVID-19 pandemic. A 44-item survey was distributed to all 11 district and regional adult and paediatric Ontario epilepsy centres. Qualitative responses were collected from community epilepsy agencies. Results revealed ongoing gaps in epilepsy care across Ontario, with EMU bed pressures and labour shortages being limiting factors. A clinical network advising the Ontario Ministry of Health will improve access to epilepsy care.

Phytohormones and related genes function as physiological and molecular switches regulating water stress response in the sunflower.

Water deficit stress reduces crop yield in field crops, including sunflowers, at any growth stage. In response, most plants activate hormonal and gene expression patterns to mitigate damage. In this study, we evaluated changes in the physiological and gene transcription levels of two sunflower (Helianthus annuus L.) inbred lines -one sensitive (B59 line) and one water stress-tolerant (B71)-in response to water stress, by using mannitol to simulate water deficit conditions, which provides moderate stress in both sunflower lines. The analyses of the accumulation of various phytohormones under this stress revealed that Jasmonic acid (JA) significantly increased in the shoots of both lines. Similarly, Salicylic acid (SA) increased in the shoots of both lines, although it also accumulated in B71 roots. In addition, Abscisic acid (ABA) and Indole-3-acetic acid (IAA) showed a considerable increase in the B59 shoots. Regarding the JA and SA pathways, the WRKY70 transcription levels were higher in the shoots of both lines and the roots of B71. The B59 line showed overtranscription of a gene related to the ABA pathway (XERICO) and genes associated with IAA (ARF9 and ARF16 genes). The B71 line, on the other hand, simultaneously triggered the JA, SA and ABA hormonal pathways in response to this stress condition. The ABA and JA hormonal pathways activated different TFs, such as RD20, RD22, RD26, ANAC19 and ANAC29, through MYC2. Both the JA and SA hormonal pathways activated the WRKY70 transcription factor. Altogether, each line triggered the hormonal and transcriptional pathways in response to water stress, although at varying intensities. The results suggest that the hormonal pathways of JA, SA, IAA and ABA, along with their primary associated genes, are activated in response to water deficit at the early growth stage in sunflower seedlings, which mitigates damage. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01497-8.

Trajectories of parent well-being in children with drug-resistant epilepsy.

OBJECTIVE: This longitudinal cohort study aimed to identify trajectories of parent well-being over the first 2 years after their child's evaluation for candidacy for epilepsy surgery, and to identify the baseline clinical and demographic characteristics associated with these trajectories. Parent well-being was based on parent depressive and anxiety symptoms and family resources (i.e., family mastery and social support). METHODS: Parents of 259 children with drug-resistant epilepsy (105 of whom eventually had surgery) were recruited from eight epilepsy centers across Canada at the time of their evaluation for epilepsy surgery candidacy. Participants were assessed at baseline and 6-month, 1-year, and 2-year follow-up. The trajectories of parents' depressive symptoms, anxiety symptoms, and family resources were jointly estimated using multigroup latent class growth models. RESULTS: The analyses identified three trajectories: an optimal-stable group with no/minimal depressive or anxiety symptoms, and high family resources that remained stable over time; a mild-decreasing-plateau group with mild depressive and anxiety symptoms that decreased over time then plateaued, and intermediate family resources that remained stable; and a moderate-decreasing group with moderate depressive and anxiety symptoms that decreased slightly, and low family resources that remained stable over time. Parents of children with higher health-related quality of life, fathers, and parents who had higher household income were more likely to have better trajectories of well-being. Treatment type was not associated with the trajectory groups, but parents whose children were seizure-free at the time of the last follow-up were more likely to have better trajectories (optimal-stable or mild-decreasing-plateau trajectories). SIGNIFICANCE: This study documented distinct trajectories of parent well-being, from the time of the child's evaluation for epilepsy surgery. Parents who present with anxiety and depressive symptoms and low family resources do not do well over time. They should be identified and offered supportive services early in their child's epilepsy treatment history.

A longitudinal cohort study of mediators of health-related quality of life after pediatric epilepsy surgery or medical treatment.

OBJECTIVES: The purpose of this longitudinal cohort study was to examine the variables that influence health-related quality of life (HRQOL) after epilepsy surgery in children. We examined whether treatment type (surgical vs medical therapy) and seizure control are related to other variables that have been shown to influence HRQOL, namely depressive symptoms in children with epilepsy or their parents, and the availability of family resources. METHODS: In total, 265 children with drug-resistant epilepsy were recruited from eight epilepsy centers across Canada at the time of their evaluation for candidacy for epilepsy surgery and were assessed at baseline, 6-month, 1-year, and 2-year follow-up. Parents completed the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55) and measures of family resources and depression; children completed depression inventories. Causal mediation analyses using natural effect models were used to evaluate the extent to which the relationship between treatment and HRQOL was explained by seizure control, child and parent depressive symptoms, and family resources. RESULTS: Overall, 111 children underwent surgery and 154 were treated with medical therapy only. The HRQOL scores of surgical patients were 3.4 points higher (95% confidence interval [CI]: -0.2, 7.0) relative to medical patients at the 2-year follow-up after adjusting for baseline covariates, with 66% of the effect of surgery attributed to seizure control. Child or parent depressive symptoms and family resources had negligible mediation effects between treatment and HRQOL. The effect of seizure control on HRQOL was not mediated by child or parent depressive symptoms, or by family resources. SIGNIFICANCE: The findings demonstrate that seizure control is on the causal pathway between epilepsy surgery and improved HRQOL in children with drug-resistant epilepsy. However, child and parent depressive symptoms and family resources were not significant mediators. The results highlight the importance of achieving seizure control to improve HRQOL.

Seizure outcome of pediatric magnetic resonance-guided laser interstitial thermal therapy versus open surgery: A matched noninferiority cohort study.

OBJECTIVE: Minimally invasive magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) has been proposed as an alternative to open epilepsy surgery, to address concerns regarding the risk of open surgery. Our primary hypothesis was that seizure freedom at 1 year after MRgLITT is noninferior to open surgery in children with drug-resistant epilepsy (DRE). The secondary hypothesis was that MRgLITT has fewer complications and shorter hospitalization than surgery. The primary objective was to compare seizure outcome of MRgLITT to open surgery in children with DRE. The secondary objective was to compare complications and length of hospitalization of the two treatments. METHODS: This retrospective multicenter cohort study included children with DRE treated with MRgLITT or open surgery with 1-year follow-up. Exclusion criteria were corpus callosotomy, neurostimulation, multilobar or hemispheric surgery, and lesion with maximal dimension > 60 mm. MRgLITT patients were propensity matched to open surgery patients. The primary outcome was seizure freedom at 1 year posttreatment. The difference in seizure freedom was compared using noninferiority test, with noninferiority margin of -10%. The secondary outcomes were complications and length of hospitalization. RESULTS: One hundred eighty-five MRgLITT patients were matched to 185 open surgery patients. Seizure freedom at 1 year follow-up was observed in 89 of 185 (48.1%) MRgLITT and 114 of 185 (61.6%) open surgery patients (difference = -13.5%, one-sided 97.5% confidence interval = -23.8% to ∞, pNoninferiority  = .79). The lower confidence interval boundary of -23.8% was below the prespecified noninferiority margin of -10%. Overall complications were lower in MRgLITT compared to open surgery (10.8% vs. 29.2%, respectively, p < .001). Hospitalization was shorter for MRgLITT than open surgery (3.1 ± 2.9 vs. 7.2 ± 6.1 days, p < .001). SIGNIFICANCE: Seizure outcome of MRgLITT at 1 year posttreatment was inferior to open surgery. However, MRgLITT has the advantage of better safety profile and shorter hospitalization. The findings will help counsel children and parents on the benefits and risks of MRgLITT and contribute to informed decision-making on treatment options.

Does the duration of video-EEG recording influence diagnostic yield in pediatric epilepsy: Results from a single center study.

AIM: This exploratory study examines the association of the duration of electroencephalography (EEG) recordings to diagnostic yield in children undergoing evaluation for seizures. METHOD: Clinical and EEG data on three hundred and ten patients (167 males and 143 females) were reviewed retrospectively. 134 (43.2%) children with focal-onset seizures, and 59 (19%) children with generalized-onset seizures. The mean duration of recordings in studies interpreted as "diagnostic" was compared to studies that were interpreted as "non-diagnostic". EMU recordings were also compared to routine EEG studies to identify the relationship between routine EEG and diagnostic studies. RESULTS: The principal finding of this study indicates that a longer duration of monitoring is more likely to be associated with a positive diagnostic yield. Mean duration of recording in children with a "non-diagnostic study" was 31.05 hours versus 44.27 hours; p < 0.001 in a "diagnostic study". EMU recordings are likely to be diagnostic with longer epilepsy duration (2.6 years vs 3.7 years; p < 0.01). A diagnostic EEG from a prolonged recording is more likely to be achieved in children with abnormal routine EEG and focal-onset seizures. p < 0.001. INTERPRETATION: Tailoring the optimal duration of EEG recordings and factoring in confounding variables will reduce the need for repeated studies, improving diagnostic utility and permitting efficient utilization of resources.

Meta-analysis of the relationship between self-critical perfectionism and depressive symptoms: Comparison between Asian American and Asian international college students.

A body of research has been dedicated to demonstrating the relationship of perfectionism with a range of mental health indicators. Self-critical perfectionism, a component of perfectionism, has been framed primarily in a negative light within the mental health context. Given that research informs educational and clinical practices, it is important to explore the degree to which such findings generalize across cultures and subcultures. The current meta-analytic research systemically collated studies conducted with Asian college students with a particular attention to exploring whether orientation to Asian culture and cultural values correspondingly moderates the relationship between self-critical perfectionism and depressive symptoms. The degree of upholding Asian cultural values was represented by group identity (i.e., Asian American and Asian international). Eleven studies (N = 3,239) were identified through the literature search. Findings from the random-effects meta-analysis indicated a significant relationship between self-critical perfectionism and depressive symptoms in the overall sample. The group identity significantly moderated the relationship; among Asian international college students, self-critical perfectionism appeared to have a less harmful effect on mental distress compared to Asian American college students. Self-cultivation-one of the salient and virtuous Asian cultural values that aligns with self-critical perfectionism-may have motivated continuous striving for self-improvement to fulfill the honorable duty for their family for Asian international students. Additional findings and implications of the study are further discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Development and validation of machine learning models for prediction of seizure outcome after pediatric epilepsy surgery.

OBJECTIVE: There is substantial variability in reported seizure outcome following pediatric epilepsy surgery, and lack of individualized predictive tools that could evaluate the probability of seizure freedom postsurgery. The aim of this study was to develop and validate a supervised machine learning (ML) model for predicting seizure freedom after pediatric epilepsy surgery. METHODS: This is a multicenter retrospective study of children who underwent epilepsy surgery at five pediatric epilepsy centers in North America. Clinical information, diagnostic investigations, and surgical characteristics were collected, and used as features to predict seizure-free outcome 1 year after surgery. The dataset was split randomly into 80% training and 20% testing data. Thirty-five combinations of five feature sets with seven ML classifiers were assessed on the training cohort using 10-fold cross-validation for model development. The performance of the optimal combination of ML classifier and feature set was evaluated in the testing cohort, and compared with logistic regression, a classical statistical approach. RESULTS: Of the 801 patients included, 61.3% were seizure-free 1 year postsurgery. During model development, the best combination was XGBoost ML algorithm with five features from the univariate feature set, including number of antiseizure medications, magnetic resonance imaging lesion, age at seizure onset, video-electroencephalography concordance, and surgery type, with a mean area under the curve (AUC) of .73 (95% confidence interval [CI] = .69-.77). The combination of XGBoost and univariate feature set was then evaluated on the testing cohort and achieved an AUC of .74 (95% CI = .66-.82; sensitivity = .87, 95% CI = .81-.94; specificity = .58, 95% CI = .47-.71). The XGBoost model outperformed the logistic regression model (AUC = .72, 95% CI = .63-.80; sensitivity = .72, 95% CI = .63-.82; specificity = .66, 95% CI = .53-.77) in the testing cohort (p = .005). SIGNIFICANCE: This study identified important features and validated an ML algorithm, XGBoost, for predicting the probability of seizure freedom after pediatric epilepsy surgery. Improved prognostication of epilepsy surgery is critical for presurgical counseling and will inform treatment decisions.

Moyamoya Syndrome in an Infant with Aicardi-Goutières and Williams Syndromes: A Case Report.

Stroke in infancy is a rare phenomenon but can lead to significant long-term disability. We present the story of a 6-month-old Old Order Amish infant with underlying Williams syndrome, a rare neurodevelopmental disorder caused by a microdeletion, encompassing the elastin gene that produces abnormalities in elastic fibers of the lungs and vessels. This infant presented with lethargy, irritability, and a new-onset generalized tonic-clonic seizure. Brain magnetic resonance imaging (MRI) was consistent with ischemic stroke in the supratentorial regions. MR angiogram demonstrated bilateral narrowing of the internal carotid arteries with "ivy sign," suggestive of Moyamoya. Moyamoya disease/syndrome is a cerebrovascular condition that is associated with progressive stenosis of the intracranial vessels and can cause ischemic stroke in young children. Targeted mutation analysis revealed a homozygous c.1411-2A > G splice site variant in the SAMHD1 gene, consistent with a diagnosis of Aicardi-Goutières syndrome type 5 (AGS5), an autosomal recessive condition with multisystem involvement. In our unique case of infantile stroke with Moyamoya syndrome and dual diagnosis of Williams syndrome and AGS5, both diagnoses likely contributed to the cerebrovascular pathology. This case report highlights the importance of suspecting and testing for multiple genetic abnormalities in children presenting with Moyamoya-related stroke.

An international consortium in epilepsy surgery education: Clinical case-based discussions between Latin-American and Canadian Epilepsy Centers.

An international consortium with a focus on Epilepsy Surgery Education was established with members from different centers in Latin America and Canada. All members of the consortium and attendees from different centers in Latin America and Canada have been meeting to discuss epilepsy surgery cases in a virtual manner. We surveyed all to assess the value of the meetings. The results and description of these meetings are being presented.

Mise en œuvre de la capacité de réponse à la COVID-19 dans un hôpital au Brésil.

After the declaration of a public health emergency of international importance, hospitals have become a benchmark in the response to the pandemic. It is important to assess health professionals' response capacity to the COVID-19 pandemic at a referral hospital in Pernambuco, in northeastern Brazil. This study deals with qualitative evaluative research, of the case study type. Three methods were used to identify critical events: interviews with 18 healthcare professionals who had worked on the "front line" of care for people with COVID-19; direct observation in the sectors of this hospital; and literature review. The interviews were transcribed and analyzed using MaxQDA Analytics pro 2020® software, using the Actor-Network Theory for analysis; and to interpret the critical events the categories of resilience: absorption, adaptation and transformation. It was found that the response capacity of professionals was influenced by five critical events: the arrival of cases, new ways to connect the patients with their social support network, social and personal impact on the daily life of professionals, insufficient supplies, essential equipment and confirmatory tests, and shortage and illness of professionals. In everyday experiences, the response capacity of professionals has led to a process of priority adaptation, which can accelerate important changes in the health system.

Longitudinal changes in emotional functioning following pediatric resective epilepsy surgery: 2-Year follow-up.

OBJECTIVE: To examine longitudinal changes and predictors of depression and anxiety 2 years following resective epilepsy surgery, compared to no surgery, in children with drug-resistant epilepsy (DRE). METHOD: This multicenter cohort study involved 128 children and adolescents with DRE (48 surgical, 80 nonsurgical; 8-18 years) who completed self-report measures of depression and anxiety at baseline and follow-up (6-month, 1-year, 2-year). Child demographic (age, sex, IQ) and seizure (age at onset, duration, frequency, site and side) variables were collected. RESULTS: Linear mixed-effects models controlling for age at enrolment found a time by treatment by seizure outcome interaction for depression. A negative linear trend across time (reduction in symptoms) was found for surgical patients, irrespective of seizure outcome. In contrast, the linear trend differed depending on seizure outcome in nonsurgical patients; a negative trend was found for those with continued seizures, whereas a positive trend (increase in symptoms) was found for those who achieved seizure freedom. Only a main effect of time was found for anxiety indicating a reduction in symptoms across patient groups. Multivariate regressions failed to find baseline predictors of depression or anxiety at 2-year follow-up in surgical patients. Older age, not baseline anxiety or depression, predicted greater symptoms of anxiety and depression at 2-year follow-up in nonsurgical patients. CONCLUSION: Children with DRE reported improvement in anxiety and depression, irrespective of whether they achieve seizure control, across the 2 years following surgery. In contrast, children with DRE who did not undergo surgery, but achieved seizure freedom, reported worsening of depressive symptoms, which may indicate difficulty adjusting to life without seizures and highlight the potential need for ongoing medical and psychosocial follow-up and support.

Pediatric Hyperacute Arterial Ischemic Stroke Pathways at Canadian Tertiary Care Hospitals.

BACKGROUND: Childhood acute arterial ischemic stroke (AIS) is diagnosed at a median of 23 hours post-symptom onset, delaying treatment. Pediatric stroke pathways can expedite diagnosis. Our goal was to understand the similarities and differences between Canadian pediatric stroke protocols with the aim of optimizing AIS management. METHODS: We contacted neurologists at all 16 Canadian pediatric hospitals regarding AIS management. Established protocols were analyzed for similarities and differences in eight domains. RESULTS: Response rate was 100%. Seven (44%) centers have an established AIS protocol and two (13%) have a protocol under development. Seven centers do not have a protocol; two redirect patients to adult neurology, five rely on a case-by-case approach for management. Analysis of the seven protocols revealed differences in: 1) IV-tPA dosage: age-dependent 0.75-0.9 mg/kg (N = 1) versus age-independent 0.9 mg/kg (N = 6), with maximum doses of 75 mg (N = 1) or 90 mg (N = 6); 2) IV-tPA lower age cut-off: 2 years (N = 5) versus 3 or 10 years (each N = 1); 3) IV-tPA exclusion criteria: PedNIHSS score <4 (N = 3), <5 (N = 1), <6 (N = 3); 4) first choice of pre-treatment neuroimaging: computed tomography (CT) (N = 3), magnetic resonance imaging (MRI) (N = 2) or either (N = 2); 5) intra-arterial tPA use (N = 3) and; 6) mechanical thrombectomy timeframe: <6 hour (N = 3), <24 hour (N = 2), unspecified (N = 2). CONCLUSIONS: Although 44% of Canadian pediatric hospitals have established AIS management pathways, several differences remain among centers. Some criteria (dosage, imaging) reflect adult AIS literature. Canadian expert consensus regarding IV-tPA and endovascular treatment should be established to standardize and implement AIS protocols across Canada.

Spatiotemporal variations in salicylic acid and hydrogen peroxide in sunflower seeds during transition from dormancy to germination.

Phytohormones and reactive oxygen species mediate processes such as germination and dormancy. The elucidation of the physiological and biochemical events implicated in the transition from dormancy to germination in different plant species such as sunflower becomes a topic of interest. In this study, we investigated the spatiotemporal variation of salicylic acid (SA), hydrogen peroxide (H2 O2 ) and the activity of two antioxidant enzymes (catalase, CAT - EC 1.11.1.6 and ascorbate peroxidase - EC 1.11.1.11) in embryonic axis and cotyledons of dry and imbibed seeds of dormant (B123) and non-dormant (B91) sunflower lines. The results showed that embryonic axis had higher level of SA and H2 O2 than cotyledons in both lines. In dry seeds, B123 embryo (embryonic axis + cotyledons) showed a higher SA content than B91. After dry storage at room temperature, SA decreased in B123 embryos to a value close to that registered in B91 embryos. B123 embryonic axis of dry seeds presented higher H2 O2 levels than B91. Dry storage led to an increase of H2 O2 levels and a decrease of CAT activity in B123 embryonic axis. During imbibition, B123 seeds stored for 33 days displayed an increase in SA level in the embryonic axis (3 h of imbibition) and this lower level correlated with a decrease in H2 O2 (6 h of imbibition). Thus, the embryo-imposed dormancy in B123 dry seeds was associated with high levels of SA and low H2 O2 , whereas the dormancy release was linked with SA decrease and increase of H2 O2 as a consequence of lower CAT activity.

Vagus nerve stimulation in patients with therapy-resistant generalized epilepsy.

BACKGROUND: For patients with generalized epilepsy who do not respond to antiseizure medications, the therapeutic options are limited. Vagus nerve stimulation (VNS) is a treatment mainly approved for therapy-resistant focal epilepsy. There is limited information on the use of VNS on generalized epilepsies, including Lennox-Gastaut Syndrome (LGS) and genetic generalized epilepsy (GGE). METHODS: We identified patients with a diagnosis of generalized epilepsy (including LGS and GGE), who underwent VNS implantation at the London Health Sciences Centre and Western University, London, Ontario, since this treatment became available in Canada in 1997 until July 2018. We assessed response to the treatment, including admissions to hospital and complications. RESULTS: A total of 46 patients were included in this study with a history of therapy-resistant generalized epilepsy. The mean age at implantation was 24 years (interquartile range [IQR] = 17.8-31 years), significantly younger in the LGS group (p = 0.02) and 50% (n = 23) were female. The most common etiologies were GGE in 37% (n = 17) and LGS in 63% (n = 29). Median follow-up since VNS implantation was 63 months (IQR: 31-112.8 months). Of the LGS group 41.7% (n = 12) of patients had an overall seizure reduction of 50% or more, and 64.7% (n = 11) in the GGE group without statistical significance between the groups. The best response in seizure reduction was seen in generalized tonic-clonic seizures, with a significant reduction in the GGE group (p = 0.043). There was a reduction of seizure-related hospital admissions from 91.3% (N = 42) preimplantation, to 43.5% (N = 20) postimplantation (p < 0.05). The frequency of side effects due to the stimulation was almost equal in both groups (62.1% in LGS and 64.7% in GGE). CONCLUSIONS: Vagus nerve stimulation should be considered as a treatment in patients with therapy-resistant generalized epilepsy, especially in cases with GGE.

Seizure freedom improves health-related quality of life after epilepsy surgery in children.

AIM: To determine whether epilepsy surgery improved health-related quality of life (HRQoL) and whether seizure freedom after surgery mediated the improvement in HRQoL. METHOD: This multicenter cohort study compared HRQoL after epilepsy surgery to pharmacological management in children with drug-resistant epilepsy (DRE). HRQoL was measured using the Quality of Life in Childhood Epilepsy (QOLCE) questionnaire at baseline and 1-year follow-up. The mediator between treatment type and HRQoL was seizure freedom. RESULTS: Two hundred and thirty-seven patients were recruited (surgery group: n=147 [92 males, 45 females]; pharmacological group: n=90 [53 males, 37 females]). Mean age at seizure onset was 6 years (SD 4y 4mo) in the surgical group and 6 years 1 month (SD 4y) in the pharmacological group. The odds ratio of seizure freedom was higher for the surgery versus pharmacological group (ß=4.24 [95% confidence interval {CI}: 2.26-7.93], p<0.001). Surgery had no direct effect on total QOLCE score at 1-year (ß=0.24 [95% CI -2.04 to 2.51], p=0.839) compared to pharmacological management, but had an indirect effect on total QOLCE that was mediated by seizure freedom (ß=0.92 [95% CI 0.19-1.65], p=0.013), adjusting for baseline total QOLCE score. Surgery had a direct effect on improving social function (p=0.043), and an indirect effect on improving physical function (p=0.016), cognition (p=0.042), social function (p=0.012) and behavior (p=0.032), mediated by seizure freedom. INTERPRETATION: Greater seizure freedom achieved through epilepsy surgery mediated the improvement in HRQoL compared to pharmacological management in children with DRE. WHAT THIS PAPER ADDS: Seizure freedom is higher after pediatric epilepsy surgery compared to pharmacologically managed epilepsy. Surgery indirectly improves health-related quality of life (HRQoL) mediated by seizure freedom compared to pharmacological management. Surgery has a direct effect on improving social function relative to pharmacological management. Baseline HRQoL was an important predictor of HRQoL after treatment.

Interventions for chronic pruritus of unknown origin.

BACKGROUND: Pruritus is a sensation that leads to the desire to scratch; its origin is unknown in 8% to 15% of affected patients. The prevalence of chronic pruritus of unknown origin (CPUO) in individuals with generalised pruritus ranges from 3.6% to 44.5%, with highest prevalence among the elderly. When the origin of pruritus is known, its management may be straightforward if an effective treatment for the causal disease is available. Treatment of CPUO is particularly difficult due to its unknown pathophysiology. OBJECTIVES: To assess the effects of interventions for CPUO in adults and children. SEARCH METHODS: We searched the following up to July 2019: Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and trials registries. We checked the reference lists of included studies for additional references to relevant trials. SELECTION CRITERIA: We sought to include randomised controlled trials and quasi-randomised controlled trials that assessed interventions for CPUO, as defined in category VI ('Other pruritus of undetermined origin, or chronic pruritus of unknown origin') of the International Forum for the Study of Itch (IFSI) classification, in children and adults. Eligible interventions were non-pharmacological or topical or systemic pharmacological interventions, and eligible comparators were another active treatment, placebo, sham procedures, or no treatment or equivalent (e.g. waiting list). DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Our primary outcomes were 'Patient- or parent-reported pruritus intensity' and 'Adverse events'. Our secondary outcomes were 'Health-related quality of life', 'Sleep disturbances', 'Depression', and 'Patient satisfaction'. We used GRADE to assess the certainty of evidence. MAIN RESULTS: We found there was an absence of evidence for the main interventions of interest: emollient creams, cooling lotions, topical corticosteroids, topical antidepressants, systemic antihistamines, systemic antidepressants, systemic anticonvulsants, and phototherapy. We included one study with 257 randomised (253 analysed) participants, aged 18 to 65 years; 60.6% were female. This study investigated the safety and efficacy of three different doses of oral serlopitant (5 mg, 1 mg, and 0.25 mg, once daily for six weeks) compared to placebo for severe chronic pruritus; 25 US centres participated (clinical research centres and universities). All outcomes were measured at the end of treatment (six weeks from baseline), except adverse events, which were monitored throughout. A pharmaceutical company funded this study. Fifty-five per cent of participants suffered from CPUO, and approximately 45% presented a dermatological diagnosis (atopic dermatitis/eczema 37.3%, psoriasis 6.7%, acne 3.6%, among other diagnoses). We unsuccessfully attempted to retrieve outcome data from study authors for the subgroup of participants with CPUO. Participants had pruritus for six weeks or longer. Total study duration was 10 weeks. Participants who received serlopitant 5 mg may have a greater rate of relief of patient-reported pruritus intensity as measured by the visual analogue scale (VAS; a reduction in VAS score indicates improvement) compared to placebo (126 participants, risk ratio (RR) 2.06, 95% confidence interval (CI) 1.27 to 3.35; low-certainty evidence). We are uncertain of the effects of serlopitant 5 mg compared to placebo on the following outcomes due to very low-certainty evidence: adverse events (127 participants; RR 1.48, 95% CI 0.87 to 2.50); health-related quality of life (as measured by the Dermatology Life Quality Index (DLQI); a higher score indicates greater impairment; 127 participants; mean difference (MD) -4.20, 95% CI -11.68 to 3.28); and sleep disturbances (people with insomnia measured by the Pittsburgh Sleep Symptom Questionnaire-Insomnia (PSSQ-I), a dichotomous measure; 128 participants; RR 0.49, 95% CI 0.24 to 1.01). Participants who received serlopitant 1 mg may have a greater rate of relief of patient-reported pruritus intensity as measured by VAS compared to placebo; however, the 95% CI indicates that there may also be little to no difference between groups (126 participants; RR 1.50, 95% CI 0.89 to 2.54; low-certainty evidence). We are uncertain of the effects of serlopitant 1 mg compared to placebo on the following outcomes due to very low-certainty evidence: adverse events (128 participants; RR 1.45, 95% CI 0.86 to 2.47); health-related quality of life (DLQI; 128 participants; MD -6.90, 95% CI -14.38 to 0.58); and sleep disturbances (PSSQ-I; 128 participants; RR 0.38, 95% CI 0.17 to 0.84). Participants who received serlopitant 0.25 mg may have a greater rate of relief of patient-reported pruritus intensity as measured by VAS compared to placebo; however, the 95% CI indicates that there may also be little to no difference between groups (127 participants; RR 1.66, 95% CI 1.00 to 2.77; low-certainty evidence). We are uncertain of the effects of serlopitant 0.25 mg compared to placebo on the following outcomes due to very low-certainty evidence: adverse events (127 participants; RR 1.29, 95% CI 0.75 to 2.24); health-related quality of life (DLQI; 127 participants; MD -5.70, 95% CI -13.18 to 1.78); and sleep disturbances (PSSQ-I; 127 participants; RR 0.60, 95% CI 0.31 to 1.17). The most commonly reported adverse events were somnolence, diarrhoea, headache, and nasopharyngitis, among others. Our included study did not measure depression or patient satisfaction. We downgraded the certainty of evidence for all outcomes due to indirectness (only 55% of study participants had CPUO) and imprecision. We downgraded outcomes other than patient-reported pruritus intensity a further level due to concerns regarding risk of bias in selection of the reported result and some concerns with risk of bias due to missing outcome data (sleep disturbances only). We deemed risk of bias to be generally low. AUTHORS' CONCLUSIONS: We found lack of evidence to address our review question: for most of our interventions of interest, we found no eligible studies. The neurokinin 1 receptor (NK1R) antagonist serlopitant was the only intervention that we could assess. One study provided low-certainty evidence suggesting that serlopitant may reduce pruritus intensity when compared with placebo. We are uncertain of the effects of serlopitant on other outcomes, as certainty of the evidence is very low. More studies with larger sample sizes, focused on patients with CPUO, are needed. Healthcare professionals, patients, and other stakeholders may have to rely on indirect evidence related to other forms of chronic pruritus when deciding between the main interventions currently used for this condition.

Anatomical Venous Variants in Children With Cerebral Sinovenous Thrombosis.

Background and Purpose- Literature is sparse on the frequency and significance of anatomical venous variants (AVVs) in pediatric cerebral sinovenous thrombosis (CSVT). Methods- We retrospectively reviewed children with CSVT and controls undergoing computed tomography/magnetic resonance venography from January 2008 to 2014. Clinical features examined included raised intracranial pressure, risk factors, and treatment. Radiological features examined included CSVT location, presence and type of AVVs, hemorrhagic venous infarction, and venous collateralization. Clinical outcome was measured by the pediatric stroke outcome measure and radiological outcome by thrombus recanalization. Results- Fifty-one children with CSVT were identified. Twenty-two (43%) had AVVs at presentation. Nineteen (86%) had hypoplasia/absence of major dural sinus, 5 (23%) had persistent fetal structures, 3 (14%) had duplications/fenestrations, and 1 (5%) had disconnected superficial and deep venous systems. Controls had a slightly higher but nonsignificant prevalence 26 (51%) of AVVs. No significant clinical and radiological differences were observed between children with CSVT and AVVs compared with those with typical venous anatomy. Conclusions- AVVs are seen in many children with and without CSVT and do not seem to alter the presentation or clinical course. The influence of these variations on the brain's ability to tolerate venous congestion because of thrombosis merits further study.

Long-Day Photoperiod Enhances Jasmonic Acid-Related Plant Defense.

Agricultural crops are exposed to a range of daylengths, which act as important environmental cues for the control of developmental processes such as flowering. To explore the additional effects of daylength on plant function, we investigated the transcriptome of Arabidopsis (Arabidopsis thaliana) plants grown under short days (SD) and transferred to long days (LD). Compared with that under SD, the LD transcriptome was enriched in genes involved in jasmonic acid-dependent systemic resistance. Many of these genes exhibited impaired expression induction under LD in the phytochrome A (phyA), cryptochrome 1 (cry1), and cry2 triple photoreceptor mutant. Compared with that under SD, LD enhanced plant resistance to the necrotrophic fungus Botrytis cinerea This response was reduced in the phyA cry1 cry2 triple mutant, in the constitutive photomorphogenic1 (cop1) mutant, in the myc2 mutant, and in mutants impaired in DELLA function. Plants grown under SD had an increased nuclear abundance of COP1 and decreased DELLA abundance, the latter of which was dependent on COP1. We conclude that growth under LD enhances plant defense by reducing COP1 activity and enhancing DELLA abundance and MYC2 expression.