Background: Childhood malnutrition is common in Malawi, and the standard treatment, which follows international guidelines, results in poor recovery rates. Higher recovery rates have been seen in ...pilot studies of home-based therapy with ready-to-use therapeutic food (RUTF). Objective: The objective was to compare the recovery rates among children with moderate and severe wasting, kwashiorkor, or both receiving either home-based therapy with RUTF or standard inpatient therapy. Design: A controlled, comparative, clinical effectiveness trial was conducted in southern Malawi with 1178 malnourished children. Children were systematically allocated to either standard therapy (186 children) or home-based therapy with RUTF (992 children) according to a stepped wedge design to control for bias introduced by the season of the year. Recovery, defined as reaching a weight-for-height z score > -2, and relapse or death were the primary outcomes. The rate of weight gain and the prevalence of fever, cough, and diarrhea were the secondary outcomes. Results: Children who received home-based therapy with RUTF were more likely to achieve a weight-for-height z score > -2 than were those who received standard therapy (79% compared with 46%; P < 0.001) and were less likely to relapse or die (8.7% compared with 16.7%; P < 0.001). Children who received home-based therapy with RUTF had greater rates of weight gain (3.5 compared with 2.0 g . kg(-1) . d(-1); difference: 1.5; 95% CI: 1.0, 2.0 g . kg(-1) . d(-1)) and a lower prevalence of fever, cough, and diarrhea than did children who received standard therapy. Conclusion: Home-based therapy with RUTF is associated with better outcomes for childhood malnutrition than is standard therapy.
Febrile infection-related epilepsy syndrome (FIRES) is a devastating epilepsy affecting normal children after a febrile illness. FIRES presents with an acute phase with super-refractory status ...epilepticus and all patients progress to a chronic phase with persistent refractory epilepsy. The typical outcome is severe encephalopathy or death. The authors present 7 children from 5 centers with FIRES who had not responded to antiepileptic drugs or other therapies who were given cannabadiol (Epidiolex, GW Pharma) on emergency or expanded investigational protocols in either the acute or chronic phase of illness. After starting cannabidiol, 6 of 7 patients’ seizures improved in frequency and duration. One patient died due to multiorgan failure secondary to isoflourane. An average of 4 antiepileptic drugs were weaned. Currently 5 subjects are ambulatory, 1 walks with assistance, and 4 are verbal. While this is an open-label case series, the authors add cannabidiol as a possible treatment for FIRES.
CDKL5 deficiency disorder (CDD) is a rare, X-linked, developmental and epileptic encephalopathy characterised by severe global developmental impairment and seizures that can begin in the first few ...months after birth and are often treatment refractory. Ganaxolone, an investigational neuroactive steroid, reduced seizure frequency in an open-label, phase 2 trial that included patients with CDD. We aimed to further assess the efficacy and safety of ganaxolone in patients with CDD-associated refractory epilepsy.
In the double-blind phase of this randomised, placebo-controlled, phase 3 trial, done at 39 outpatient clinics in eight countries (Australia, France, Israel, Italy, Poland, Russia, the UK, and the USA), patients were eligible if they were aged 2–21 years with a pathogenic or probably pathogenic CDKL5 variant and at least 16 major motor seizures (defined as bilateral tonic, generalised tonic-clonic, bilateral clonic, atonic, or focal to bilateral tonic-clonic) per 28 days in each 4-week period of an 8-week historical period. After a 6-week prospective baseline period, patients were randomly assigned (1:1) via an interactive web response system to receive either enteral adjunctive ganaxolone or matching enteral adjunctive placebo (maximum dose 63 mg/kg per day for patients weighing ≤28 kg or 1800 mg/day for patients weighing >28 kg) for 17 weeks. Patients, caregivers, investigators (including those analysing data), trial staff, and the sponsor (other than the investigational product manager) were masked to treatment allocation. The primary efficacy endpoint was percentage change in median 28-day major motor seizure frequency from the baseline period to the 17-week double-blind phase and was analysed (using a Wilcoxon-rank sum test) in all patients who received at least one dose of trial treatment and for whom baseline data were available. Safety (compared descriptively across groups) was analysed in all patients who received at least one dose of trial treatment. This study is registered with ClinicalTrials.gov, NCT03572933, and the open-label extension phase is ongoing.
Between June 25, 2018, and July 2, 2020, 114 patients were screened for eligibility, of whom 101 (median age 6 years IQR 3 to 10) were randomly assigned to receive either ganaxolone (n=50) or placebo (n=51). All patients received at least one dose of a study drug, but seizure frequency for one patient in the ganaxolone group was not recorded at baseline and so the primary endpoint was analysed in a population of 100 patients. There was a median percentage change in 28-day major motor seizure frequency of –30·7% (IQR –49·5 to –1·9) in the ganaxolone group and of –6·9% (–24·1 to 39·7) in the placebo group (p=0·0036). The Hodges–Lehmann estimate of median difference in responses to ganaxolone versus placebo was –27·1% (95% CI –47·9 to – 9·6). Treatment-emergent adverse events occurred in 43 (86%) of 50 patients in the ganaxolone group and in 45 (88%) of 51 patients in the placebo group. Somnolence, pyrexia, and upper respiratory tract infections occurred in at least 10% of patients in the ganaxolone group and more frequently than in the placebo group. Serious adverse events occurred in six (12%) patients in the ganaxolone group and in five (10%) patients in the placebo group. Two (4%) patients in the ganaxolone group and four (8%) patients in the placebo group discontinued the trial. There were no deaths in the double-blind phase.
Ganaxolone significantly reduced the frequency of CDD-associated seizures compared with placebo and was generally well tolerated. Results from what is, to our knowledge, the first controlled trial in CDD suggest a potential treatment benefit for ganaxolone. Long-term treatment is being assessed in the ongoing open-label extension phase of this trial.
Marinus Pharmaceuticals.
Circumstances of the COVID-19 pandemic have mandated a change to standard management of infantile spasms. On April 6, 2020, the Child Neurology Society issued an online statement of immediate ...recommendations to streamline diagnosis and treatment of infantile spasms with utilization of telemedicine, outpatient studies, and selection of first-line oral therapies as initial treatment. The rationale for the recommendations and specific guidance including follow-up assessment are provided in this manuscript. These recommendations are indicated as enduring if intended to outlast the pandemic, and limited if intended only for the pandemic health care crisis but may be applicable to future disruptions of health care delivery.
Palliative Epilepsy Surgery Procedures in Children Matern, Tyson S.; DeCarlo, Rebecca; Ciliberto, Michael A. ...
Seminars in pediatric neurology,
October 2021, 2021-10-00, 20211001, Letnik:
39
Journal Article
Recenzirano
Surgical treatment of epilepsy typically focuses on identification of a seizure focus with subsequent resection and/or disconnection to “cure” the patient's epilepsy and achieve seizure freedom. ...Palliative epilepsy surgery modalities are efficacious in improving seizure frequency, severity, and quality of life. In this paper, we review palliative epilepsy surgical options for children: vagus nerve stimulation, responsive neurostimulation, deep brain stimulation, hemispherotomy, corpus callosotomy, lobectomy and/or lesionectomy and multiple subpial transection. Reoperation after surgical resection should also be considered. If curative resection is not a viable option for seizure freedom, these methods should be considered with equal emphasis and urgency in the treatment of drug-resistant epilepsy.
Objective
Drug‐resistant epilepsy (DRE) occurs at higher rates in children <3 years old. Epilepsy surgery is effective, but rarely utilized in young children despite developmental benefits of early ...seizure freedom. The present study aims to identify unique patient characteristics and evaluation strategies in children <3 years old who undergo epilepsy surgery evaluation as a means to assess contributors and potential solutions to health care disparities in this group.
Methods
The Pediatric Epilepsy Research Consortium Epilepsy Surgery Database, a multicentered, cross‐sectional collaboration of 21 US pediatric epilepsy centers, collects prospective data on children <18 years of age referred for epilepsy surgery evaluation. We compared patient characteristics, diagnostic utilization, and surgical treatment between children <3 years old and those older undergoing initial presurgical evaluation. We evaluated patient characteristics leading to delayed referral (>1 year) after DRE diagnosis in the very young.
Results
The cohort included 437 children, of whom 71 (16%) were <3 years of age at referral. Children evaluated before the age of 3 years more commonly had abnormal neurological examinations (p = .002) and daily seizures (p = .001). At least one ancillary test was used in 44% of evaluations. Fifty‐nine percent were seizure‐free following surgery (n = 34), with 35% undergoing limited focal resections. Children with delayed referrals more often had focal aware (p < .001) seizures and recommendation for palliative surgeries (p < .001).
Significance
There are relatively few studies of epilepsy surgery in the very young. Surgery is effective, but may be disproportionally offered to those with severe presentations. Relatively low utilization of ancillary testing may contribute to reduced surgical therapy for those without evident lesions on magnetic resonance imaging. Despite this, a sizeable portion of patients have favorable outcome after focal epilepsy surgery resections.
Objectives
Corpus callosotomy (CC) is used to reduce seizures, primarily in patients with generalized drug‐resistant epilepsy (DRE). The invasive nature of the procedure contributes to ...underutilization despite its potential superiority to other palliative procedures. The goal of this study was to use a multi‐institutional epilepsy surgery database to characterize the use of CC across participating centers.
Methods
Data were acquired from the Pediatric Epilepsy Research Consortium (PERC) Surgery Database, a prospective observational study collecting data on children 0–18 years referred for surgical evaluation of DRE across 22 U.S. pediatric epilepsy centers. Patient, epilepsy, and surgical characteristics were collected across multiple CC modalities. Outcomes and complications were recorded and analyzed statistically.
Results
Eighty‐three patients undergoing 85 CC procedures at 14 participating epilepsy centers met inclusion criteria. Mean age at seizure onset was 2.3 years (0–9.4); mean age for Phase I evaluation and surgical intervention were 9.45 (.1–20) and 10.46 (.2–20.6) years, respectively. Generalized seizure types were the most common (59%). Complete CC was performed in 88%. The majority of CC procedures (57%) were via open craniotomy, followed by laser interstitial thermal therapy (LiTT) (20%) and mini‐craniotomy/endoscopic (mc/e) (22%). Mean operative times were significantly longer for LiTT, whereas mean estimated blood loss was greater in open cases. Complications occurred in 11 cases (13%) and differed significantly between surgical techniques (p < .001). There was no statistically significant difference in length of postoperative stay across approaches. Mean follow‐up was 12.8 months (range 1–39). Favorable Engel outcomes were experienced by 37 (78.7%) of the patients who underwent craniotomy, 10 (58.8%) with LiTT, and 12 (63.2%) with mc/e; these differences were not statistically significant.
Significance
CC is an effective surgical modality for children with DRE. Regardless of surgical modality, complication rates are acceptable and seizure outcomes generally favorable. Newer, less‐invasive, surgical approaches may lead to increased adoption of this efficacious therapeutic option for pediatric DRE.
Objective
Persons with drug‐resistant epilepsy may benefit from epilepsy surgery and should undergo presurgical testing to determine potential candidacy and appropriate intervention. Institutional ...expertise can influence use and availability of evaluations and epilepsy surgery candidacy. This census survey study aims to examine the influence of geographic region and other center characteristics on presurgical testing for medically intractable epilepsy.
Methods
We analyzed annual report and supplemental survey data reported in 2020 from 206 adult epilepsy center directors and 136 pediatric epilepsy center directors in the United States. Test utilization data were compiled with annual center volumes, available resources, and US Census regional data. We used Wilcoxon rank‐sum, Kruskal–Wallis, and chi‐squared tests for univariate analysis of procedure utilization. Multivariable modeling was also performed to assign odds ratios (ORs) of significant variables.
Results
The response rate was 100% with individual element missingness < 11% across 342 observations undergoing univariate analysis. A total of 278 complete observations were included in the multivariable models, and significant regional differences were present. For instance, compared to centers in the South, those in the Midwest used neuropsychological testing (OR = 2.87, 95% confidence interval CI = 1.2–6.86; p = .018) and fluorodeoxyglucose–positron emission tomography (OR = 2.74, 95% CI = = 1.14–6.61; p = .025) more commonly. For centers in the Northeast (OR = .46, 95% CI = .23–.93; p = .031) and West (OR = .41, 95% CI = .19–.87; p = .022), odds of performing single‐photon emission computerized tomography were lower by nearly 50% compared to those in the South. Center accreditation level, demographics, volume, and resources were also associated with varying individual testing rates.
Significance
Presurgical testing for drug‐resistant epilepsy is influenced by US geographic region and other center characteristics. These findings have potential implications for comparing outcomes between US epilepsy centers and may inject disparities in access to surgical treatment.
Nearly one-third of persons with epilepsy will continue having seizures despite trialing multiple antiseizure medications. Epilepsy surgery may be beneficial in these cases, and evaluation at a ...comprehensive epilepsy center is recommended. Numerous palliative and potentially curative approaches exist, and types of surgery performed may be influenced by center characteristics. This article describes epilepsy center characteristics associated with epilepsy surgery access and volumes in the United States.
We analyzed National Association of Epilepsy Centers 2019 annual report and supplemental survey data obtained with responses from 206 adult epilepsy center directors and 136 pediatric epilepsy center directors in the United States. Surgical treatment volumes were compiled with center characteristics, including US Census region. We used multivariable modeling with zero-inflated Poisson regression models to present ORs and incidence rate ratios of receiving a given surgery type based on center characteristics.
The response rate was 100% with individual element missingness less than 4% across 352 observations undergoing univariate analysis. Multivariable models included 319 complete observations. Significant regional differences were present. The rates of laser interstitial thermal therapy (LITT) were lower at centers in the Midwest (incidence rate ratio IRR 0.74, 95% CI 0.59-0.92;
= 0.006) and Northeast (IRR 0.77, 95% CI 0.61-0.96;
= 0.022) compared with those in the South. Conversely, responsive neurostimulation implantation rates were higher in the Midwest (IRR 1.45, 95% CI 1.1-1.91;
= 0.008) and West (IRR 1.91, 95% CI 1.49-2.44;
< 0.001) compared with the South. Center accreditation level, institution type, demographics, and resources were also associated with variations in access and rates of potentially curative and palliative surgical interventions.
Epilepsy surgery procedure volumes are influenced by US epilepsy center region and other characteristics. These variations may affect access to specific surgical treatments for persons with drug resistant epilepsy across the United States.
Immunotherapies have emerged as one of the most promising approaches to treat patients with cancer. Recently, the entire medical oncology field has been revolutionized by the introduction of immune ...checkpoints inhibitors. Despite success in a variety of malignancies, responses typically only occur in a small percentage of patients for any given histology or treatment regimen. There are also concerns that immunotherapies are associated with immune-related toxicity as well as high costs. As such, identifying biomarkers to determine which patients are likely to derive clinical benefit from which immunotherapy and/or be susceptible to adverse side effects is a compelling clinical and social need. In addition, with several new immunotherapy agents in different phases of development, and approved therapeutics being tested in combination with a variety of different standard of care treatments, there is a requirement to stratify patients and select the most appropriate population in which to assess clinical efficacy. The opportunity to design parallel biomarkers studies that are integrated within key randomized clinical trials could be the ideal solution. Sample collection (fresh and/or archival tissue, PBMC, serum, plasma, stool, etc.) at specific points of treatment is important for evaluating possible biomarkers and studying the mechanisms of responsiveness, resistance, toxicity and relapse. This white paper proposes the creation of a network to facilitate the sharing and coordinating of samples from clinical trials to enable more in-depth analyses of correlative biomarkers than is currently possible and to assess the feasibilities, logistics, and collated interests. We propose a high standard of sample collection and storage as well as exchange of samples and knowledge through collaboration, and envisage how this could move forward using banked samples from completed studies together with prospective planning for ongoing and future clinical trials.
PDF
