Angelina Kakooza-Mwesige

A new type of epilepsy syndrome, an etiology‐specific epilepsy syndrome, was defined in 2022 in recognition of major advances in identifying the many genetic and acquired etiologies underlying the epilepsies. An etiology‐specific epilepsy syndrome refers to where a known etiology is associated with a distinctive epilepsy presentation, including age at seizure onset, seizure types, and other morbidities, such as learning difficulties or intellectual disability, psychiatric features, gut and musculoskeletal problems. However, as we understand more about a specific etiology, such as a gene, it is clear that many etiologies are associated not just with one epilepsy syndrome, but with a range of epilepsy syndromes. Different epilepsy syndromes due to an abnormality in the same gene may reflect different types of dysfunction caused by the specific pathogenic genetic variant. Here, we expand the concept because—knowing the genetic etiology is not enough to ensure optimal clinical care—it requires a more nuanced approach to ensure the patient is managed appropriately. We define the concept of an etiology‐specific spectrum of epilepsy syndromes (ESSES), which incorporates understanding the range of epilepsy syndromes that may be associated with a specific etiology. In some cases, a genetic etiology may be associated with a functional spectrum, such as pathogenic variants in an ion channel subunit that cause loss‐of‐function, gain‐of‐function, or mixed functional effects, each associated with specific epilepsy syndromes that may require different treatment approaches. With other genes, the functional effect may not yet be known, but their spectrum of epilepsy syndromes may be well established through genotype–phenotype studies. The concept of ESSES has the flexibility to grow in its scope with new insights gained from understanding the breadth of epilepsy syndromes associated with a specific etiology and the associated functional impact.

Aim: To relate the trial‐based costs of the Akwenda Intervention Program, a multi‐component, community‐based intervention for children and young people with cerebral palsy (CP) in rural Uganda, to multiple prespecified child and caregiver outcomes. Method: An economic evaluation was conducted within a cluster‐randomized, assessor‐blinded trial of 94 participants with CP (aged 2–23 years; 42 females) and their caregivers, allocated to intervention or usual care. Programme delivery costs were assessed from a restricted health care or provider perspective; selected out‐of‐pocket costs incurred by participating families were reported separately over 12 months. Outcome‐specific incremental cost‐effectiveness ratios (ICERs) were estimated for child outcomes (66‐item Gross Motor Function Measure, Pediatric Evaluation of Disability Inventory [Ugandan version], and Picture My Participation) and caregiver outcomes (Zimbabwe Caregiver Challenges Scale and Pediatric Quality of Life Inventory Family Impact Module). Uncertainty was assessed using bootstrapping, cost‐effectiveness planes, and exploratory acceptability curves. Costs were also determined per minimal clinically important difference (MCID) gained. Results: The mean incremental cost per child was US$1069 to US$1075. Outcome‐specific ICERs ranged from US$26 to US$352 per unit of improvement for 10 of 11 outcomes; the Pediatric Evaluation of Disability Inventory (Ugandan version) mobility had a higher and highly uncertain ICER. Costs per MCID gained ranged from US$230 to US$600. Acceptability analyses were presented as exploratory uncertainty analyses because no established Uganda‐specific willingness‐to‐pay thresholds exist for these outcome measures. Interpretation: The Akwenda Intervention Program improved child functioning, participation, and caregiver well‐being at additional but predictable costs. This trial‐based economic evaluation quantifies the costs associated with improvement across multiple prespecified outcomes and provides economic information relevant to the implementation of community‐based rehabilitation in low‐resource settings.

The classification of the epilepsies has traditionally relied on clinical and electroencephalographic features. However, advancements in molecular genetics, neuroimaging, and our understanding of epilepsy pathophysiology necessitate a shift toward an etiology‐based approach. Etiology‐specific classification enables precision diagnosis and precision management by integrating genetic, structural, metabolic, infection, and immune‐related insights. Genetic advances have identified more than 1000 epilepsy‐related genes, revealing how variations in a single gene can produce diverse phenotypes and syndromes. Similarly, neuroimaging innovations, such as high‐resolution magnetic resonance imaging and functional imaging, have enhanced detection of subtle structural abnormalities and epileptogenic zones. In 2022, the International League Against Epilepsy introduced the concept of etiology‐specific epilepsy syndromes, emphasizing the interplay between etiology and syndrome. This paradigm shift moves beyond traditional classifications, offering tailored treatments that address seizures and comorbidities to improve prognosis and quality of life. Despite this progress, challenges persist. These include the complexity of defining genotype–phenotype functional relationships, limitations in diagnostic accessibility in resource‐limited settings, and the integration of multifactorial causes. This article proposes extending the concept of etiology‐specific epilepsy syndromes to encompass broader spectrums of phenotypes within each etiology, supported by detailed frameworks for analyzing clinical, imaging, genetic, and functional data. The aim is to refine the classification system to guide personalized, evidence‐based care. This etiology–syndromic spectrum model underscores the importance of lifelong, multidisciplinary approaches to epilepsy management, balancing the value of syndrome‐based insights with the transformative potential of precision medicine.

Background: Mortality among children under 5 years in sub-Saharan Africa (SSA) has declined substantially since 2000, but progress in the developmental status of surviving children under the Sustainable Development Goals, 2015-2030 (SDGs) remains unclear. This paper examines mortality and disability among children under 5 years in SSA to inform regional global health priorities. Methods: We conducted a sub-regional and national analysis of the Global Burden of Disease Study (GBD) 2023 for all 48 countries in SSA to compare changes in all-cause mortality, developmental disabilities, and Years Lived with Disability (YLDs) between 2000 and 2023. The prevalence of attention-deficit/hyperactivity disorder, autism spectrum disorder, developmental intellectual disability, epilepsy, hearing loss, vision loss and aggregate disabilities in 2023 was also analysed. Estimates are reported with 95% uncertainty intervals. Findings: Whereas child mortality declined by 31.1% (30.0 to 32.2) from 3.8 million (95% UI:3.8–3.9) in 2000 to 2.6 million (2.6–2.7) in 2023, the number of children with a disability rose by 67.0% (22.9–127.1) from 7.0 million (6.0–8.5) in 2000 to 11.6 million (9.6–15.9) in 2023, representing a 6.4% (5.3-8.7) prevalence. YLDs rose by 74.3% (1.5–199.2) from 0.8 million (0.6–1.1) to 1.4 million (1.0–2.3) within this period. In 2023, the prevalence of developmental disabilities and YLDs was greatest in Eastern SSA. Some 61.2% of children with disabilities resided in the ten top countries, collectively accounting for 67.2% of the region’s child mortality. Nigeria, the Democratic Republic of Congo, and Ethiopia accounted for the most overlapping burden of child mortality and disability. Hearing loss was the most prevalent disability (2.4% [2.1-2.6]), affecting 4.3 million (3.8–4.8) children. Epilepsy was associated with the greatest YLDs. Interpretation: The growing burden of developmental disabilities in SSA calls for global action to place the affected children on a trajectory for optimal development and inclusive learning, as mandated by the SDGs. Improved primary data sources and surveillance systems are also required for more precise disability estimates.

Background Epilepsy affects 70 million people worldwide, 80% of whom are in low-and-middle income countries (LMICs). Parasitic infections contribute considerably to the burden of epilepsy in LMICs, but the nature and presentation of epilepsy following these infections is not fully understood. We examined if epilepsy outcomes are associated with the exposure to parasitic infections. Methods This was a case-comparison study nested in a cross-sectional survey of people with active convulsive epilepsy, with cases as those exposed to parasitic infections, and comparison as those unexposed. Associations of exposure to parasites with clinical and electroencephalographic features of epilepsy were done using a modified mixed effects Poisson regression model across five sites in Africa. Multiplicative and additive scale (RERI) interactions were explored to determine the effect of co-infections on epilepsy features. Population attributable fractions (PAF) were calculated to determine the proportion of severe clinical and electroencephalographic features of epilepsy attributable to parasitic infections. Results A total of 997 participants with active convulsive epilepsy from the five African sites were analyzed, 51% of whom were males. Exposure to parasitic infections was associated with more frequent seizures in adult epilepsy (relative risk (RR) = 2.58, 95% confidence interval (95%CI): 1.71–3.89). In children, exposure to any parasite was associated with convulsive status epilepticus (RR = 4.68, (95%CI, 3.79–5.78), intellectual disabilities (RR = 2.13, 95%CI: 1.35–3.34) and neurological deficits (RR = 1.92, 95%CI: 1.42–2.61). Toxoplasma gondii and Onchocerca volvulus interacted synergistically to increase the risk of status epilepticus (RERI = 0.91, 95%CI = 0.48–1.35) in the data pooled across the sites. Exposure to parasitic infections contributed to 30% of severe features of epilepsy as shown by PAF. Conclusions Parasitic infections may be associated with features and phenotypes of epilepsy through synergistic or antagonistic interactions, which can be different in children and adults. Interventions to control or manage infections may reduce complications and improve prognosis in people with epilepsy.

To describe the implementation of goal-directed therapy (GDT) and provision of assistive devices (ADs) within the Akwenda Intervention Program, a structured community-based rehabilitation program, and to examine goal attainment, AD use, and caregiver perspectives in a rural setting in eastern Uganda. This study included 50 children and young people aged 2-23 years with cerebral palsy. The intervention formed part of an 11-month multi-component program including caregiver training, therapist-led sessions, communication and advocacy, GDT, and AD-provision. Therapists received structured training in collaborative goal setting using Goal Attainment Scaling (GAS). ADs, including wheelchairs, standing frames, posture support chairs, walkers, orthoses, and toileting devices, were provided with training and follow-up. Goal attainment was evaluated using GAS, while AD use and caregiver satisfaction were assessed through usage diaries and a structured questionnaire. A total of 146 goals were set, of which 63% were achieved. Most goals targeted activity (56%) and participation (32%). Participants with milder motor impairments demonstrated higher goal attainment than those with more severe impairments (p = 0.04). Goal attainment was moderately associated with reduced caregiver assistance in self-care (r = 0.41, p = 0.006) and reduced caregiver burden (r = 0.40, p = 0.008), but not with other child-related outcomes. Twenty-four participants received 66 ADs, of which 85% remained in use after six months. Caregiver satisfaction exceeded 80% across domains. GDT and AD-provision were feasible to implement within a community-based rehabilitation program in a rural Ugandan setting, supporting meaningful functional outcomes.

Background: Over 50 million children under five have disabilities, the majority residing in resource-limited settings. Many children with neurodevelopmental disabilities (NDDs) remain undetected due to lack of culturally appropriate tools for identification. This study aimed to develop and evaluate the feasibility of the Identification of Neurodevelopmental Disabilities to Improve Global Outcomes (INDIGO) tool to identify NDDs in children aged 0 −3 years. Methods: A systematic approach was used to construct the INDIGO tool. First, 114 items of the Malawi Developmental Assessment Tool (MDAT) were mapped onto the International Classification of Functioning, Disability and Health for Children and Youth (ICF-CY). Gaps were identified leading to review of 2,158 items from existing tools. After consensus, 59 additional items (28 existing, 31 newly created) were incorporated, ensuring comprehensive coverage of ICF-CY domains. The preliminary INDIGO tool (203 items) was pilot tested in Uganda, Malawi and Pakistan with a gold standard assessment protocol developed to validate diagnostic accuracy. Feasibility outcomes including recruitment, diagnostic accuracy, cultural applicability and practical implementation were assessed. Items with over 80% diagnostic accuracy were retained for the final INDIGO prototype. Results: A total of 425 children (151 Malawi, 145 Pakistan, 129 Uganda) were assessed using both INDIGO and gold standard evaluation. The feasibility study highlighted challenges in recruiting younger children with behavioural or socioemotional conditions and difficulties assessing sensory impairment due to resource constraints. Despite challenges, 99 high performing items were selected for the final INDIGO prototype emphasizing diagnostic accuracy, feasibility and cultural neutrality. Conclusions: The INDIGO tool is a novel, rigorously developed instrument designed for early detection of NDDs in children 0-3 years in LMICs. By integrating a broad range of developmental domains, INDIGO addressed key limitations of existing tools. Future large-scale validation and implementation studies are needed to assess its effectiveness in routine child health surveillance programmes. Key Messages: What is already known on this topic: Most existing developmental screening tools used globally are not culturally adapted for LMICs, require specialized training, and fail to comprehensively assess structural, functional, and environmental factors important for detecting NDDs in early childhood. What this study adds: This study presents the development and feasibility testing of the INDIGO tool, a novel screening instrument for identifying moderate to severe NDDs in children under 3 years in resource-limited settings, incorporating items to assess structural anomalies, sensory impairments, and participation, offering a more holistic and contextually relevant approach to NDD detection. The study provides strong initial evidence of diagnostic accuracy across multiple LMIC settings, with high feasibility and acceptability among caregivers and health workers. How this study might affect research, practice or policy: Future studies could enable scaled up implementation of tools such as INDIGO integrated into national child health systems for early NDD detection, enhancing referral and intervention in LMICs.

Introduction: Childhood disability is increasingly prevalent, particularly in low-income and middle-income countries, as more children survive worldwide. Global practice guidelines are essential to address the need for timely identification, evaluation and management of children with developmental disabilities, particularly in resource-limited settings. This scoping review aims to summarise recent evidence-based practice guidelines for the assessment and care of children aged 0–5 years at risk or with developmental disabilities and identify those practice guidelines that are suitable for use across both global and resource-limited settings. Methods: We searched PubMed, Scopus, CINAHL as well as websites for professional associations using Google to identify evidence-based practice guidelines for specific developmental disabilities with established global prevalence estimates. We identified additional literature through snowballing. Practice guidelines were included if they were published between September 2012 and June 2024, were in English, and demonstrated a systematic process of reviewing available evidence, which then provided information on the detection, diagnosis, treatment and management of children under five with developmental disabilities. Three reviewers independently screened results by title, abstract and full text. Study characteristics and outcome data were extracted, and results were narratively synthesised. Results: 43 practice guidelines met the eligibility search criteria. Few evidence-based practice guidelines were generated from resource-limited settings (n=3, 7.0%). Of these, two were published in Malaysia and one from Cameroon. Most of the practice guidelines focused on both assessment and management (n=20, 46.5%), with some addressing only assessment (n=9, 20.9%) or management of the conditions (n=14, 32.6%). Conclusions: Practice guidelines focusing on the identification and support of children with developmental disabilities, chiefly published within high-income settings, are available to be selectively adapted and utilised across similar localities globally. All young children with developmental disabilities worldwide have the right to access equitable, timely and quality health and developmental care services.