Screening for developmental delay in urban Rwandan children: a cross sectional study.

BACKGROUND: Systematic or targeted screening for developmental delay (DD) is critical to the early identification of developmental disabilities. With limited available information for urban Rwandan children, this study aimed to determine the prevalence of DD and associated risk factors in infants aged 9 to 16 months living in the urban Rwandan city of Kigali. METHODS: A cross-sectional study was conducted in Rwanda from August to November 2019. A convenience sample of 376 Rwandan parents/caregivers and their children attending urban health centers for their routine immunization visits at 9 and 15 months of age was studied. Parents/caregivers completed the official Kinyarwandan version of the Ages and Stages Questionnaire (ASQ-3) and established cutoffs were used to identify DD. Frequency and percentages were used to summarise the data. Logistic regression analysis was used to identify factors associated with DD. RESULTS: Of the 358 children screened using the ASQ-3, the overall prevalence of DD was 24.6%, with a 27.2% prevalence among 9-10-month old children and 22.4% prevalence among 15-16-month old children. Delays in the combined group among the domains of gross motor, communication, fine motor, personal social, and problem solving were 12.8%, 2.5%, 8.4%, 1.7% and 7.5%, respectively. Gestational age at delivery and district of origin were most highly associated with DD, with preterm children at significantly higher risk of having DD compared to term children (Adjusted Odd Ratio AOR = 8.3; 95% CI = 2.5-27.4) and children from Nyarugenge District at high risk of DD compared to children from Gasabo district (AOR = 2.15; 95% CI = 1.2-3.9). CONCLUSIONS: The prevalence of ASQ-detectable DD among urban Rwandan children between 9 and 16 months of age was 24.6%, with a high correlation to a history of prematurity and district of origin. This study demonstrates the need for thoughtful health planning regarding integrated developmental surveillance for children, particularly those at high risk, to allow for earlier identification and intervention in the urban area of Kigali, Rwanda.

Survey on the worldwide availability and affordability of antiseizure medications: Report of the ILAE Task Force on Access to Treatment.

Health systems worldwide are challenged in the provision of basic medical services and access to treatments for chronic conditions. Epilepsy, the most common severe chronic neurological disorder, does not receive sufficient attention despite being officially declared a public health priority by the World Health Organization. More than 80% of people with epilepsy live in middle- and low-income countries (MICs and LICs, respectively), where most of the population lacks reliable access to antiseizure medications (ASMs), contributing significantly to the large epilepsy treatment gap in these regions. The International League Against Epilepsy (ILAE) Task Force on Access to Treatment administered a global survey to report on the current access to ASMs worldwide. The survey was developed and distributed online through the ILAE and International Bureau of Epilepsy (IBE) secretariats to the chapter representatives. The survey was completed by one representative per country. Response rate was 73.2% (101 countries of the 138 represented in ILAE and/or IBE organizations). Availability and access of ASMs, including distribution problems and costs, reimbursement procedures, general barriers to access to care, and presence of projects targeted toward improving care access, were studied, and descriptive statistics on available responses were performed. Among the 15 first-generation ASMs surveyed, carbamazepine was reported as the most widely available globally. At least one first-generation ASM is widely available in most countries, but their number differs dramatically across income levels. Second- and third-generation ASMs are even more limited in MICs and LICs. Additionally, average retail prices for ASMs were not significantly different across countries despite the differences in per capita income from high-income countries to LICs. This survey provides a worrisome picture of availability and accessibility of ASMs across the world, with wide disparities according to socioeconomic status. Recommendations for direct action on improving access to care will be discussed.

EEG markers predictive of epilepsy risk in pediatric cerebral malaria - A feasibility study.

OBJECTIVE: Cerebral malaria (CM) affects 500,000 million children annually, 10% whom develop epilepsy within two years. Acute identification of biomarkers for post-CM epilepsy would allow for follow-up of the highest risk populations in resource-limited regions. We investigated the utility of electroencephalogram (EEG) and clinical metrics obtained during acute CM infection for predicting epilepsy. METHODS: We analyzed 70 EEGs recorded within 24 h of admission for CM hospitalization obtained during the Blantyre Malaria Project Epilepsy Study (2005-2007), a prospective cohort study of pediatric CM survivors. While all studies underwent spectral analyses for comparisons of mean power band frequencies, a subset of EEGs from the 10 subjects who developed epilepsy and 10 age- and sex-matched controls underwent conventional visual analysis. Findings were tested for relationships to epilepsy outcomes. RESULTS: Ten of the 70 subjects developed epilepsy. There were no significant differences between groups that were analyzed via visual EEG review; however, spectral EEG analyses revealed a significantly higher gamma-delta power ratio in CM survivors who developed epilepsy (0.23 ±â€¯0.10) than in those who did not (0.16 ±â€¯0.06), p = 0.003. Excluding potential confounders, multivariable logistic-regression analyses found relative gamma power (p = 0.003) and maximum temperature during admission (p = 0.03) significant and independent predictors of post-CM epilepsy, with area under receiver operating characteristics (AUROC) curve of 0.854. CONCLUSIONS: We found that clinical and EEG metrics acquired during acute CM presentation confer risk of post-CM epilepsy. Further studies are required to investigate the utility of gamma activity as a potential biomarker of epileptogenesis and study this process over time. Additionally, resource limitations currently prevent follow-up of all CM cases to surveil for epilepsy, and identification of acute biomarkers in this population would offer the opportunity to allocate resources more efficiently.

Global Health: Pediatric Neurology.

Neurologic disorders contribute significantly to both morbidity and mortality among children in resource-limited settings, but there are a few succinct studies summarizing the epidemiology of neurologic disorders in these settings. A review of available literature was performed to identify data on the prevalence, etiology, outcomes, and treatment of neurologic disorders in children in resource-limited settings. The burden of neurologic disorders in children is high in resource-limited settings. Barriers to optimal care include lack of trained personnel, limited access to diagnostic technology, and limited availability of drugs used to treat common conditions. Several solutions have been suggested to deal with these challenges including increased collaborations to train neurologists willing to practice in resource-limited settings and increased training of physician extenders or community health workers. Further studies are necessary to improve our understanding of the epidemiology of neurologic disorders in resource-limited settings. Future epidemiologic studies should incorporate multiple countries in resource-limited settings and utilize standardized definitions and methodologies to enable comparison across regions.

A pediatric epilepsy diagnostic tool for use in resource-limited settings: A pilot study.

OBJECTIVE: It is estimated that nearly 80% of the 50 million people affected with epilepsy globally live in regions where specialist care and diagnostic tests are scarce and care is often delivered through a primary health provider with limited training. To improve diagnostic accuracy of the history and physical examination, we developed and piloted a questionnaire to discriminate between focal versus generalized epilepsy, with the future goal to guide medication choices. METHODS: Through literature review and retrospective chart review of 75 children with epilepsy at Boston Children's Hospital, a 15-item questionnaire was developed. Simple motor seizures were excluded for the purposes of this questionnaire. The questionnaire was then translated in local dialects and prospectively validated at Muhimbili National Hospital in Dar Es Salaam, Tanzania, and University Teaching Hospital in Lusaka, Zambia. Children 6months-18years of age with suspected or active epilepsy were identified, and a nonphysician administered the questionnaire to the patient's caregiver. Next, each patient was evaluated by a pediatric neurologist blinded to the questionnaire results, and together with locally obtained but remotely interpreted EEG, an electroclinical diagnosis was made. The questionnaire data were compared with this clinical gold standard. RESULTS: A total of 59 children participated: 28 from Tanzania and 31 from Zambia. Sixteen patients were excluded: 5 were excluded because of incomplete data, and 11 did not meet criteria for epilepsy based on initial screening questions. Of the remaining 43 patients, 28 had focal or multifocal epilepsy (65%), and 15 (35%) had generalized epilepsy. The questionnaire had a sensitivity of 78% and positive predictive value of 81.5%. Data were analyzed using a Rasch model, testing the questionnaire's internal consistency, reliability, and its discriminative validity in classifying focal versus generalized epilepsy against an electroclinical diagnosis. The mean epilepsy score for focal epilepsy was 0.084 logits compared with -1.147 logits for generalized epilepsy, demonstrating a large effect size [F (1, 41)=13.490, p<0.001]. CONCLUSIONS: Our questionnaire provides a straightforward method to improve diagnostic accuracy, and could assist in bridging the diagnostic gap in pediatric epilepsy in resource-limited settings. This tool was specifically designed to be easily implemented by any healthcare provider. This pilot study prompts broader prospective validation in additional settings for further refinement, and for performance assessment of impact on provider's practice, ability to guide medication choices, and ultimately improve treatment outcomes in resource-limited regions.

Acetaminophen and Ibuprofen in Pediatric Central Nervous System Malaria: A Randomized Clinical Trial.

Importance: A third of children who survive malaria with neurological involvement (central nervous system [CNS] malaria) develop sequelae. A higher maximum temperature (Tmax) and seizures are risk factors for sequelae. Objective: To compare aggressive antipyretic therapy using scheduled acetaminophen and ibuprofen vs usual care with acetaminophen alone given only for a temperature of 38.5 °C or higher. Design, Setting, and Participants: This randomized clinical trial was conducted at inpatient pediatric services of 1 tertiary care and 1 district hospital in Zambia and a tertiary care center in Malawi. Included were children aged 2 to 11 years with CNS malaria (excluding those with creatinine >1.2 mg/dL), who were enrolled from 2019 to 2022. Data analysis took place from December 2022 to April 2023. Intervention: The aggressive antipyretic group received acetaminophen (30 mg/kg load, then 15 mg/kg) plus ibuprofen, 10 mg/kg, every 6 hours, regardless of clinical temperature for 72 hours. The usual care group received 15 mg/kg of acetaminophen as needed every 6 hours for a temperature of 38.5 °C or higher. Main Outcomes and Measures: The primary outcome variable was Tmax over 72 hours, the total duration of follow-up. Secondary outcomes included seizures and parasite clearance. Results: Five hundred fifty-three patients were screened, 226 (40.9%) were ineligible, and 57 (10.3%) declined. A total 256 participants (n = 128/group) had a mean (SD) age of 4.3 (2.1) years; 115 (45%) were female, and 141 (55%) were male. The aggressive antipyretic group had a lower Tmax, 38.6 vs 39.2 °C (difference, -0.62 °C; 95% CI, -0.82 to -0.42; P < .001) and lower odds of experiencing multiple or prolonged seizures, 10 (8%) vs 34 children (27%) in the usual care group (odds ratio [OR], 0.26; 95% CI, 0.12 to 0.56). No group difference in parasite clearance time was detected. Severe adverse events occurred in 40 children (15%), 25 (20%) in the usual care group and 15 (12%) in the aggressive antipyretic group, including 13 deaths (10 [8%] and 3 [2%], respectively). Increased creatinine resulted in study drug discontinuation in 8 children (6%) in the usual care group and 13 children (10%) in the aggressive antipyretic group (OR, 1.74; 95% CI, 0.63 to 5.07). Conclusions and Relevance: This study found that aggressive antipyretic therapy reduced mean Tmax to temperature levels comparable with the Tmax among children without neurological impairments in prior observational studies and improved acute seizure outcomes with no prolongation of parasitemia. Trial Registration: ClinicalTrials.gov Identifier: NCT03399318.

Protocol for a magnetic resonance imaging study of participants in the fever RCT: Does fever control prevent brain injury in malaria?

BACKGROUND: Despite eradication efforts, ~135,000 African children sustained brain injuries as a result of central nervous system (CNS) malaria in 2021. Newer antimalarial medications rapidly clear peripheral parasitemia and improve survival, but mortality remains high with no associated decline in post-malaria neurologic injury. A randomized controlled trial of aggressive antipyretic therapy with acetaminophen and ibuprofen (Fever RCT) for malarial fevers being conducted in Malawi and Zambia began enrollment in 2019. We propose to use neuroimaging in the context of the RCT to further evaluate neuroprotective effects of aggressive antipyretic therapy. METHODS: This observational magnetic resonance imaging (MRI) ancillary study will obtain neuroimaging and neurodevelopmental and behavioral outcomes in children previously enrolled in the Fever RCT at 1- and 12-months post discharge. Analysis will compare the odds of any brain injury between the aggressive antipyretic therapy and usual care groups based upon MRI structural abnormalities. For children unable to undergo imaging without deep sedation, neurodevelopmental and behavioral outcomes will be used to identify brain injury. DISCUSSION: Neuroimaging is a well-established, valid proxy for neurological outcomes after brain injury in pediatric CNS malaria. This MRI ancillary study will add value to the Fever RCT by determining if treatment with aggressive antipyretic therapy is neuroprotective in CNS malaria. It may also help elucidate the underlying mechanism(s) of neuroprotection and expand upon FEVER RCT safety assessments.

Protocol for a Magnetic Resonance Imaging (MRI) Study of Participants in the Fever Randomized Controlled Trial: Does fever control prevent brain injury in malaria?

Background: Despite eradication efforts, ~135,000 African children sustained brain injuries as a result of central nervous system (CNS) malaria in 2021. Newer antimalarial medications rapidly clear peripheral parasitemia and improve survival, but mortality remains high with no associated decline in post-malaria neurologic injury. A randomized controlled trial of aggressive antipyretic therapy with acetaminophen and ibuprofen (Fever RCT) for malarial fevers being conducted in Malawi and Zambia began enrollment in 2019. We propose to use neuroimaging in the context of the RCT to further evaluate neuroprotective effects of aggressive antipyretic therapy. Methods: This observational magnetic resonance imaging (MRI) ancillary study will obtain neuroimaging and neurodevelopmental and behavioral outcomes in children previously enrolled in the Fever RCT at 1- and 12-months post discharge. Analysis will compare the odds of any brain injury between the aggressive antipyretic therapy and usual care groups based upon MRI structural abnormalities. For children unable to undergo imaging without deep sedation, neurodevelopmental and behavioral outcomes will be used to identify brain injury. Discussion: Neuroimaging is a well-established, valid proxy for neurological outcomes after brain injury in pediatric CNS malaria. This MRI ancillary study will add value to the Fever RCT by determining if treatment with aggressive antipyretic therapy is neuroprotective in CNS malaria. It may also help elucidate the underlying mechanism(s) of neuroprotection and expand upon FEVER RCT safety assessments.

Consensus Competencies for Postgraduate Fellowship Training in Global Neurology.

BACKGROUND AND OBJECTIVES: Use a modified Delphi approach to develop competencies for neurologists completing ≥1 year of advanced global neurology training. METHODS: An expert panel of 19 United States-based neurologists involved in global health was recruited from the American Academy of Neurology Global Health Section and the American Neurological Association International Outreach Committee. An extensive list of global health competencies was generated from review of global health curricula and adapted for global neurology training. Using a modified Delphi method, United States-based neurologists participated in 3 rounds of voting on a survey with potential competencies rated on a 4-point Likert scale. A final group discussion was held to reach consensus. Proposed competencies were then subjected to a formal review from a group of 7 neurologists from low- and middle-income countries (LMICs) with experience working with neurology trainees from high-income countries (HICs) who commented on potential gaps, feasibility, and local implementation challenges of the proposed competencies. This feedback was used to modify and finalize competencies. RESULTS: Three rounds of surveys, a conference call with United States-based experts, and a semistructured questionnaire and focus group discussion with LMIC experts were used to discuss and reach consensus on the final competencies. This resulted in a competency framework consisting of 47 competencies across 8 domains: (1) cultural context, social determinants of health and access to care; (2) clinical and teaching skills and neurologic medical knowledge; (3) team-based practice; (4) developing global neurology partnerships; (5) ethics; (6) approach to clinical care; (7) community neurologic health; (8) health care systems and multinational health care organizations. DISCUSSION: These proposed competencies can serve as a foundation on which future global neurology training programs can be built and trainees evaluated. It may also serve as a model for global health training programs in other medical specialties as well as a framework to expand the number of neurologists from HICs trained in global neurology.

Recommendations for treatment strategies in people with epilepsy during times of shortage of antiseizure medications

In times of severe antiseizure medication (ASM) shortage due to emergency situations (e.g., disasters, conflicts, sudden disruption to international supply chains), management of people with epilepsy with available ASMs can be difficult. A group of experts was brought together by the International League Against Epilepsy (ILAE) to formulate recommendations for such circumstances. Every effort was made to base these recommendations on direct published literature or extrapolations from basic information available about ASMs. Actual published literature in this area is, however, limited, and at times, assumptions were made by the experts to generate these recommendations. During times of shortage of ASMs, switching between different ASMs (e.g., oxcarbazepine and carbamazepine) can occasionally be considered as a mitigation procedure. However, for many ASMs, the option of an overnight switch to another drug does not exist. Switching from brand to generic or between generic products has often been shown to be safe, if required. Finally, when supplies of benzodiazepines or equipment to administer medications intravenously are not available, rectal administration of some ASMs may be an emergency alternative route for treating serial seizures and status epilepticus. Decision-making with regard to treatment and possible options should be driven by what is best for the patient.

Identifying biomarkers for epilepsy after cerebral malaria in Zambian children: rationale and design of a prospective observational study.

INTRODUCTION: Malaria affecting the central nervous system (CM) is a major contributor to paediatric epilepsy in resource-poor settings, with 10%-16% of survivors developing epilepsy within 2 years of infection. Despite high risk for post-malaria epilepsy (PME), biomarkers indicating which CM survivors will develop epilepsy are absent. Such biomarkers are essential to identify those at highest risk who might benefit most from close surveillance and/or preventive treatments. Electroencephalography (EEG) contains signals (specifically gamma frequency activity), which are correlated with higher risk of PME and provide a biomarker for the development of epilepsy. We propose to study the sensitivity of quantitative and qualitative EEG metrics in predicting PME, and the potential increased sensitivity of this measure with additional clinical metrics. Our goal is to develop a predictive PME index composed of EEG and clinical history metrics that are highly feasible to obtain in low-resourced regions. METHODS AND ANALYSES: This prospective observational study being conducted in Eastern Zambia will recruit 250 children aged 6 months to 11 years presenting with acute CM and follow them for two years. Children with pre-existing epilepsy diagnoses will be excluded. Outcome measures will include qualitative and quantitative analysis of routine EEG recordings, as well as clinical metrics in the acute and subacute period, including histidine-rich protein 2 levels of parasite burden, depth and length of coma, presence and severity of acute seizures, presence of hypoglycaemia, maximum temperature and 1-month post-CM neurodevelopmental assessment scores. We will test the performance of these EEG and clinical metrics in predicting development of epilepsy through multivariate logistic regression analyses. ETHICS AND DISSEMINATION: This study has been approved by the Boston Children's Hospital Institutional Review Board, University of Zambia Biomedical Research Ethics Committee, and National Health Research Authority of Zambia. Results will be disseminated locally in Zambia followed by publication in international, open access, peer-reviewed journals when feasible.

Magnetic resonance imaging-guided laser-induced thermal therapy for functional hemispherotomy in a child with refractory epilepsy and multiple medical comorbidities.

Magnetic resonance imaging-guided laser-induced thermal therapy (MRgLITT) is a minimally invasive surgical approach increasingly employed for precise targeted ablation of epileptogenic brain foci. Recent reports have described corpus callosotomy using MRgLITT, though its application in more extensive functional disconnections has not been documented. Here, the authors detail its use in achieving a palliative hemispherotomy in a 5-year-old with medically refractory hemiclonic seizures following a hemispheric infarction, highlighting a novel use of this surgical technique. In this particular case, open craniotomy was deemed high risk given the multiple medical comorbidities including congenital cardiac disease and end-stage renal failure. MRgLITT was considered an alternative approach with a lower risk for periprocedural hemodynamic perturbations. The patient tolerated the procedure well, attaining an Engel class IB outcome at 16 months' follow-up. This suggests that MRgLITT may be an alternative approach to an open hemispherectomy, particularly in cases in which multiple comorbidities pose significant risks and preclude an open procedure.

Bone Health Screening Practices Among Neurologists in Patients on Antiepileptic Drugs: A Quality Improvement Project.

BACKGROUND: Pediatric patients with epilepsy are at risk for low vitamin D levels, increasing the risk for bone fractures, yet standardized bone health screening is not part of routine care. METHODS: We surveyed pediatric neurologists (n = 68) at our center regarding screening practices, using an 11-item survey; constructed a bone health treatment algorithm; and developed a training intervention to improve screening rates. RESULTS: The overall survey response rate was 47%. Among respondents, 64% estimated that they screened for bone health less than 25% of the time. Chart review before the intervention demonstrated an overall screening rate of 25.1% (n = 50/199). One year after implementation of a standardized algorithm, the overall screening rates increased to 53.8% (n = 100/186). The frequency of prescribing vitamin D for patients treated with antiepileptic medications increased among general neurologists (preintervention rate 16%, postintervention rate 51%, P < 0.01) as well as among epileptologists (preintervention rate 45%, postintervention rate 57%, P = 0.04). CONCLUSION: In a relatively short follow-up period, there were significant changes in care patterns regarding screening for bone health in pediatric patients with epilepsy. Further implementation measures are underway to increase bone health screening and care in this population.

Ketogenic diet in Zambia: Managing drug-resistant epilepsy in a low and middle income country.

Globally, drug-resistant epilepsy affects one third of people living with epilepsy. With limitations in treatment options for refractory epilepsy in resource-limited regions, ketogenic diet therapy is an important option to consider. Utilizing the 2015 International League Against Epilepsy recommended minimum requirements for ketogenic diet therapy, three male children with refractory epilepsy, aged 2.5, 6.5 and 10 years, were initiated on the classical ketogenic diet using locally available food in August 2017 at University Teaching Hospitals-Children's Hospital in Lusaka, Zambia, through partnership with the Epilepsy Program at Boston Children's Hospital in the United States. Following successful initiation in all three children, the diet was discontinued in the 10-year-old due to difficulties complying with the diet. The youngest child demonstrated an over 50% seizure reduction and gained developmental milestones. The third child achieved seizure freedom and showed marked improvement in behaviour. This pilot demonstrates the feasibility of ketogenic diet as an important therapeutic option for refractory epilepsy in Zambia. Given the limitations in treatment choices and medication accessibility, dietary therapy offers an alternative management strategy in our setting. Collaboration with an established ketogenic diet centre contributes to a successful program.

Development and Evaluation of a Pediatric Epilepsy Training Program for First Level Providers in Zambia.

Introduction. The developing world continues to face challenges in closing the large treatment gap for epilepsy, due to a high burden of disease and few experienced providers to manage the condition. Children with epilepsy are susceptible to higher rates of developmental impairments and refractory disease due to delays or absence of appropriate management as a result. We demonstrated that a structured education intervention on pediatric epilepsy can improve knowledge, confidence, and impact clinical practice of first level providers in Zambia. Methods. Three first-level facilities across Zambia were included. After initial pilot versions and revisions, the final course was implemented at each site. Pre- and post-intervention knowledge and confidence assessments were performed. Additionally, chart reviews were conducted prior to intervention and 4 months after completion of training at each site to assess change on management. Results. Twenty-three of the original 24 participants from all 3 sites completed the training; 48% clinical officers, 43% nurses, 9% other expertise. Of the 15 concepts tested by knowledge assessment, 12 showed trends in improvement, 7 of which were significant (P < .05). Chart reviews demonstrated significant improvement in documentation of seizure description (P = .008), seizure frequency (P = .00), and possible causes of seizures/epilepsy (P = .034). Discussion. Key elements of success to this program included hands on clinical skills building and case-based teaching, development of a program with direct and ongoing input from the target audience, and inclusion of assessments to monitor impact on clinical practice. Future studies looking at health outcomes are necessary to determine sustained impact.

Focal epilepsy features in a child with Congenital Zika Syndrome.

Zika virus (ZIKV) is a mosquito-borne, single-stranded DNA flavivirus that is teratogenic and neurotropic. Similar to the teratogenic effects of other TORCH infections, ZIKV infection during pregnancy can have an adverse impact on fetal and neonatal development. Epilepsy is detected in 48-96% of children with Congenital Zika Syndrome (CZS) and microcephaly. Early epilepsy surveillance is needed in children with prenatal ZIKV exposure; yet, most ZIKV-endemic regions do not have specialist epilepsy care. Here, we describe the demographic, clinical, imaging, and EEG characteristics of a 2-year-old child with CZS and microcephaly who presented with focal epileptiform activity, suboptimal growth, and severe neurodevelopmental delays. Administration of a brief seizure questionnaire by allied health professionals to the patient's caregiver helped to characterize the child's seizure semiology and differentiate focal from generalized seizure features. A telemedicine EEG interpretation platform provided valuable diagnostic information for the patient's local pediatrician to integrate into her treatment plan. This case illustrates that CZS can present with focal epilepsy features and that a telemedicine approach can be used to bridge the gap between epilepsy specialists and local care providers in resource limited ZIKV-endemic regions to achieve better seizure control in children with CZS.

Epilepsy surveillance in normocephalic children with and without prenatal Zika virus exposure.

Children with Congenital Zika Syndrome and microcephaly are at high risk for epilepsy; however, the risk is unclear in normocephalic children with prenatal Zika virus (ZIKV) exposure [Exposed Children (EC)]. In this prospective cohort study, we performed epilepsy screening in normocephalic EC alongside a parallel group of normocephalic unexposed children [Unexposed Children (UC)]. We compared the incidence rate of epilepsy among EC and UC at one year of life to global incidence rates. Pregnant women were recruited from public health centers during the ZIKV outbreak in Grenada, West Indies and assessed for prior ZIKV infection using a plasmonic-gold platform that measures IgG antibodies in serum. Normocephalic children born to mothers with positive ZIKV results during pregnancy were classified as EC and those born to mothers with negative ZIKV results during and after pregnancy were classified as UC. Epilepsy screening procedures included a pediatric epilepsy screening questionnaire and video electroencephalography (vEEG). vEEG was collected using a multi-channel microEEG® system for a minimum of 20 minutes along with video recording of participant behavior time-locked to the EEG. vEEGs were interpreted independently by two pediatric epileptologists, who were blinded to ZIKV status, via telemedicine platform. Positive screening cases were referred to a local pediatrician for an epilepsy diagnostic evaluation. Epilepsy screens were positive in 2/71 EC (IR: 0.028; 95% CI: 0.003-0.098) and 0/71 UC. In both epilepsy-positive cases, questionnaire responses and interictal vEEGs were consistent with focal, rather than generalized, seizures. Both children met criteria for a clinical diagnosis of epilepsy and good seizure control was achieved with carbamazepine. Our results indicate that epilepsy rates are modestly elevated in EC. Given our small sample size, results should be considered preliminary. They support the use of epilepsy screening procedures in larger epidemiological studies of children with congenital ZIKV exposure, even in the absence of microcephaly, and provide guidance for conducting epilepsy surveillance in resource limited settings.

Keeping people with epilepsy safe during the COVID-19 pandemic.

OBJECTIVES: To provide information on the effect of the coronavirus disease of 2019 (COVID-19) pandemic on people with epilepsy and provide consensus recommendations on how to provide the best possible care for people with epilepsy while avoiding visits to urgent care facilities and hospitalizations during the novel coronavirus pandemic. METHODS: The authors developed consensus statements in 2 sections. The first was "How should we/clinicians modify our clinical care pathway for people with epilepsy during the COVID-19 pandemic?" The second was "What general advice should we give to people with epilepsy during this crisis? The authors individually scored statements on a scale of -10 (strongly disagree) to +10 (strongly agree). Five of 11 recommendations for physicians and 3/5 recommendations for individuals/families were rated by all the authors as 7 or above (strongly agree) on the first round of rating. Subsequently, a teleconference was held where statements for which there was a lack of strong consensus were revised. RESULTS: After revision, all consensus recommendations received a score of 7 or above. The recommendations focus on administration of as much care as possible at home to keep people with epilepsy out of health care facilities, where they are likely to encounter COVID-19 (including strategies for rescue therapy), as well as minimization of risk of seizure exacerbation through adherence, and through ensuring a regular supply of medication. We also provide helpful links to additional helpful information for people with epilepsy and health providers. CONCLUSION: These recommendations may help health care professionals provide optimal care to people with epilepsy during the coronavirus pandemic.

Improving paediatric epilepsy management at the first level of care: a pilot education intervention for clinical officers in Zambia.

OBJECTIVE: Epilepsy affects approximately 50 million people globally, with approximately 80% living in low/middle-income countries (LMIC), where access to specialist care is limited. In LMIC, primary health workers provide the majority of epilepsy care, despite limited training in this field. Recognising this knowledge gap among these providers is an essential component for closing the epilepsy treatment gap in these regions. SETTING: In Zambia, the vast majority of healthcare is provided by clinical officers (COs), primary health providers with 3 years post-secondary general medical education, who predominantly work in first-level health centres around the country. PARTICIPANTS: With cooperation from the Ministry of Health, a total of 10 COs from 4 surrounding first-level health centres around the capital city of Lusaka participated, with 9 completing the entire course. INTERVENTION: COs were trained in a 3-week structured course on paediatric seizures and epilepsy, based on adapted evidence-based guidelines. RESULTS: Preassessment and postassessment were conducted to assess the intervention. Following the course, there was improved overall knowledge about epilepsy (69% vs 81%, p<0.05), specifically knowledge regarding medication management and recognition of focal seizures (p<0.05), improved seizure history taking and appropriate medication titration (p<0.05). However, knowledge regarding provoked seizures, use of diagnostic studies and general aetiologies of epilepsy remained limited. CONCLUSIONS: This pilot project demonstrated that a focused paediatric epilepsy training programme for COs can improve knowledge and confidence in management, and as such is a promising step for improving the large epilepsy treatment gap in children in Zambia. With feasibility demonstrated, future projects are needed to expand to more rural regions for more diverse and larger sample of primary health provider participants and encompass more case-based training and repetition of key concepts as well as methods to improve and assess long-term knowledge retention.

Bridging the childhood epilepsy treatment gap in northern Nigeria (BRIDGE): Rationale and design of pre-clinical trial studies.

Epilepsy is the most common serious childhood neurological disorder. In the low- and middle-income countries (LMICs) of Africa, children with epilepsy suffer increased morbidity and mortality compared to their counterparts in high-income countries, and the majority do not receive treatment - the childhood epilepsy treatment gap. Reports of the childhood epilepsy treatment gap in Africa are likely underestimates; most surveys do not include several common childhood seizure types, including most types of non-convulsive epilepsy. Efforts to scale up childhood epilepsy care services in the LMICs of Africa must contend with a shortage of physicians and diagnostic technology [e.g., electroencephalograms (EEGs)]. One pragmatic solution is to integrate epilepsy care into primary care by task-shifting to community health extension workers. The aims of this project (BRIDGE) are to: 1) train, develop, and pilot task-shifted epilepsy care teams; 2) develop and pilot innovative childhood epilepsy screening and diagnostic paradigms adapted to the local Hausa language/culture in Kano, northern Nigeria; and, 3) quantify and map the childhood epilepsy treatment gap, using geographic information systems (GIS), to target limited resources to areas of greatest need. Task-shifted teams will diagnose and manage childhood epilepsy using an innovative epilepsy screening tools and diagnostic and management paradigms in environments with limited EEG access. If validated and demonstrated efficacious in clinical trials, this project can be taken to scale across broader areas of west Africa's LMICs that share language and culture. BRIDGE has the potential to enhance access to basic childhood epilepsy care and establish the foundation for childhood epilepsy clinical trials in west Africa.