The International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st) Project is a population-based, longitudinal study describing early growth and development in an optimally healthy cohort of 4607 mothers and newborns. At 24 months, children are assessed for neurodevelopmental outcomes with the INTERGROWTH-21st Neurodevelopment Package. This paper describes neurodevelopment tools for preschoolers and the systematic approach leading to the development of the Package.

Background: People living with HIV are at risk of developing HIV-associated neurocognitive disorders (HAND) which adversely affects their quality of life. Routine screening of HAND in HIV care is recommended to identify clinically important changes in cognitive functioning and allow for early interventions. However, HAND detection in routine clinical practice has never been reported in sub-Saharan Africa (SSA), partly due to a lack of adequately standardized screening tools. This review was conducted to identify the commonly used screening tools for HAND in SSA and document their psychometric properties and diagnostic accuracy. Methods: We searched Ovid Medline, PsycINFO and Web of Sciences databases for empirical studies published from 1/1/1980 to 31/8/2018 on HAND among adults living with HIV in SSA. Results: We identified 14 eligible studies, of which 9 were from South Africa. The International HIV Dementia Scale (IHDS) was the most frequently reported tool, being used in more than half of the studies. However most studies only reported the diagnostic accuracy of this and other tools, with specificity ranging from 37% to 81% and sensitivity ranging from 45% to 100%. Appropriate data on construct validity and reliability of tools was rarely documented. Although most tools performed well in screening for severe forms of HAND, they lacked sensitivity and specificity for mild forms of HAND. NeuroScreen, one of the newer tools, yielded good diagnostic accuracy in its initial evaluation in South Africa (81% to 93% sensitivity and 71% to 81% specificity). Conclusions: This review identified a lack of adequately standardized and contextually relevant HAND screening tools in SSA. Most screening tools for HAND used in SSA possess inadequate psychometric properties and diagnostic accuracy. There is a need for further validation of existing tools and development of new HAND screening tools in SSA.

Introduction: The growing impact of non-communicable diseases in low- to middle-income countries makes epilepsy a key research priority. We evaluated peer-reviewed published literature on childhood epilepsy specific to Kenya to identify knowledge gaps and inform future priorities. Methodology: A literature search utilizing the terms "epilepsy" OR "seizure" as exploded subject headings AND "Kenya" was conducted. Relevant databases were searched, generating 908 articles. After initial screening to remove duplications, irrelevant articles, and publications older than 15 years, 154 papers remained for full-article review, which identified 35 publications containing relevant information. Data were extracted from these reports on epidemiology, etiology, clinical features, management, and outcomes. Results: The estimated prevalence of lifetime epilepsy in children was 21-41 per 1,000, while the incidence of active convulsive epilepsy was 39-187 cases per 100,000 children per year. The incidence of acute seizures was 312-879 per 100,000 children per year and neonatal seizures 3,950 per 100,000 live births per year. Common risk factors for both epilepsy and acute seizures included adverse perinatal events, meningitis, malaria, febrile seizures, and family history of epilepsy. Electroencephalography abnormalities were documented in 20%-41% and neurocognitive comorbidities in more than half. Mortality in children admitted with acute seizures was 3%-6%, and neurological sequelae were identified in 31% following convulsive status epilepticus. Only 7%-29% children with epilepsy were on antiseizure medication. Conclusion: Active convulsive epilepsy is a common condition among Kenyan children, remains largely untreated, and leads to extremely poor outcomes. The high proportion of epilepsy attributable to preventable causes, in particular neonatal morbidity, contributes significantly to the lifetime burden of the condition. This review reaffirms the ongoing need for better public awareness of epilepsy as a treatable disease and for national-level action that targets both prevention and management.

Evidence from high-income countries demonstrates that co-morbid mental disorders in people with epilepsy adversely affect clinical and social outcomes. However, evidence from low-income countries is lacking. The objective of this study was to measure the association between co-morbid mental disorders and quality of life and functioning in people with epilepsy.

The Millennium Developmental Goals ensured a significant reduction in childhood mortality. However, this reduction simultaneously raised concerns about the long-term outcomes of survivors of early childhood insults. This systematic review focuses on the long-term neurocognitive and mental health outcomes of neonatal insults (NNI) survivors who are six years or older.

Timely detection and management of comorbid mental disorders in people with epilepsy is essential to improve outcomes. The objective of this study was to measure the performance of primary health care (PHC) workers in identifying comorbid mental disorders in people with epilepsy against a standardised reference diagnosis and a screening instrument in rural Ethiopia.

Globally, epilepsy is the most common chronic neurological disorder. The incidence in sub-Saharan Africa is 2-3 times higher than that in high income countries. Infection by Onchocerca volvulus may be an underlying risk factor for the high burden and based upon epidemiological associations, has been proposed to cause a group of disorders-Onchocerca associated epilepsies (OAE) like nodding syndrome (NS). To improve our understanding of the disease spectrum, we described the clinical, electroencephalographic (EEG) and magnetic resonance imaging (MRI) features of children with epilepsy and sero-positive for Onchocerca volvulus (possible OAEs other than nodding syndrome). Twenty-nine children and adolescents with non-nodding syndrome OAE in northern Uganda were enrolled. A diagnosis of OAE was made in patients with epilepsy and seizure onset after age 3 years, no reported exposure to perinatal severe febrile illness or traumatic brain injury, no syndromic epilepsy diagnosis and a positive Ov-16 ELISA test. Detailed clinical evaluation including psychiatric, diagnostic EEG, a diagnostic brain MRI (in 10 patients) and laboratory testing were performed. Twenty participants (69%) were male. The mean age was 15.9 (standard deviation [SD] 1.9) years while the mean age at seizure onset was 9.8 (SD 2.9) years. All reported normal early childhood development. The most common clinical presentation was a tonic-clonic seizure. The median number of seizures was 2 (IQR 1-4) in the previous month. No specific musculoskeletal changes, or cranial nerve palsies were reported, neither were any vision, hearing and speech difficulties observed. The interictal EEG was abnormal in the majority with slow wave background activity in 52% (15/29) while 41% (12/29) had focal epileptiform activity. The brain MRI showed mild to moderate cerebellar atrophy and varying degrees of atrophy of the frontal, parietal and occipital lobes. The clinical spectrum of epilepsies associated with Onchocerca may be broader than previously described. In addition, focal onset tonic-clonic seizures, cortical and cerebellar atrophy may be important brain imaging and clinical features.

Stroke is the second leading cause of death globally. Computerized tomography is used to distinguish between ischemic and hemorrhagic subtypes, but it is expensive and unavailable in low and middle income countries. Clinical stroke scores are proposed to differentiate between stroke subtypes but their reliability is unknown.

A high level of unmet communication need exists amongst children with developmental disabilities in sub-Saharan Africa. This study investigated preliminary evidence of the impact associated with a home-based, caregiver-implemented intervention employing AAC methods, with nine children in rural Kenya who have complex communication needs. The intervention used mainly locally-sourced low-tech materials, and was designed to make use of the child's strengths and the caregiver's natural expertise. A pretest-posttest design was used in the study. Data were gathered using an adapted version of the Communication Profile, which was based on the International Classification of Functioning, Disability, and Health (ICF) framework. The non-parametric Wilcoxon signed-rank test was applied to data from the first two sections of the Communication Profile-Adapted. Qualitative analysis was conducted on the final section. The data provided evidence of statistically significant positive changes in caregiver perceptions of communication at the levels of Body Structure and Function, and Activities for Communication. Also, analysis of the Participation for Communication section revealed some expansion to the children's social activities. The potential impact of the home-based intervention would benefit from investigation on a larger scale. Limitations of the study are discussed.

Substantial evidence indicates that parents of autistic individuals often display milder forms of autistic traits referred to as the broader autism phenotype (BAP). To determine if discrete endophenotypes of autism can be identified, we reviewed the literature to assess the evidence of behavioral, cognitive, and psychiatric profiles of the BAP. A systematic review was conducted using EMBASE, MEDLINE, PsycINFO, PsycEXTRA, and Global Health. Sixty papers met our inclusion criteria and results are discussed according to the proportion of studies that yield significant deficits per domain. The behavioral, cognitive, and psychiatric endophenotypes in parents of autistic probands are still not clarified; however, evidence suggests mild social/communication deficits, rigid/aloof personality traits, and pragmatic language difficulties as the most useful sociobehavioral candidate endophenotype traits. The existence of deficits in the cognitive domain does suggest familial vulnerability for autism. Furthermore, increased depressed mood and anxiety can also be useful markers; however, findings should be interpreted with caution because of the small number of studies in such heterogeneously broad domains and several methodological limitations.

Health risk behavior (HRB) is of concern during adolescence. In sub-Saharan Africa, reliable, valid and culturally appropriate measures of HRB are urgently needed. This study aims at assembling and psychometrically evaluating a comprehensive questionnaire on HRB of adolescents in Kilifi County at the coast of Kenya.

The prevalence of CD36 deficiency in East Asian and African populations suggests that the causal variants are under selection by severe malaria. Previous analysis of data from the International HapMap Project indicated that a CD36 haplotype bearing a nonsense mutation (T1264G; rs3211938) had undergone recent positive selection in the Yoruba of Nigeria. To investigate the global distribution of this putative selection event, we genotyped T1264G in 3420 individuals from 66 populations. We confirmed the high frequency of 1264G in the Yoruba (26%). However, the 1264G allele is less common in other African populations and absent from all non-African populations without recent African admixture. Using long-range linkage disequilibrium, we studied two West African groups in depth. Evidence for recent positive selection at the locus was demonstrable in the Yoruba, although not in Gambians. We screened 70 variants from across CD36 for an association with severe malaria phenotypes, employing a case-control study of 1350 subjects and a family study of 1288 parent-offspring trios. No marker was significantly associated with severe malaria. We focused on T1264G, genotyping 10,922 samples from four African populations. The nonsense allele was not associated with severe malaria (pooled allelic odds ratio 1.0; 95% confidence interval 0.89-1.12; P = 0.98). These results suggest a range of possible explanations including the existence of alternative selection pressures on CD36, co-evolution between host and parasite or confounding caused by allelic heterogeneity of CD36 deficiency.

The aim of this study was to describe the normative development of the electrophysiological response to auditory and visual novelty in children living in rural Kenya.

Neurological complications due to chikungunya virus (CHIKV) infection have been described in different parts of the world, with children being disproportionately affected. However, the burden of CHIKV-associated neurological disease in Africa is currently unknown and given the lack of diagnostic facilities in routine care it is possible that CHIKV is an unrecognized etiology among children with encephalitis or other neurological illness.

To search for antibodies against neuronal cell surface proteins.

Epilepsy is one of the most common neurological conditions globally, estimated to constitute 0.75% of the global burden of disease, with the majority of this burden found in low- and middle- income countries (LMICs). Few studies from LMICs, including much of sub-Saharan Africa, have described the incidence, remission or mortality rates due to epilepsy, which are needed to quantify the burden and inform policy. This study investigates the epidemiological parameters of convulsive epilepsy within a context of high HIV prevalence and an emerging burden of cardiovascular disease.

The burden of autism spectrum disorders (ASDs) in sub-Saharan Africa (SSA) is not well known. We carried out a systematic review of the literature to identify published work from SSA. We have systematically searched four databases, namely, Medline, PsycINFO, CINAHL, and Child Development & Adolescent Studies, through EBSCO and identified studies from across SSA. Based on predefined inclusion criteria, 47 studies were included in this review. Most of the identified studies (74%) were conducted in only 2 African countries, that is, South Africa and Nigeria. Additionally, most of these studies (83%) were carried out in the last decade. These studies had four major themes: development of measurement tools of ASD in Africa, examining the prevalence of ASD, identifying risk factors and risk markers, and examining psychosocial issues. We identified only a single population level study aimed at documenting the prevalence of ASD and could not identify a single case-control study aimed at examining a comprehensive set of potential risk factors. All intervention studies were based on very small sample sizes. Put together, our findings suggest that current evidence base is too scanty to provide the required information to plan adequately for effective intervention strategies for children with ASD in Africa.

The upsurge in the uptake of antiretroviral therapy (ART) has led to a significant increase in the survival of vertically acquired HIV infected children, many of whom are currently living into adolescence and early adulthood. However little if anything is known of the lived experiences and the challenges faced by HIV positive adolescents in the African context. We set out to investigate psychosocial challenges faced by HIV infected adolescents on the Kenyan coast.

Antibodies that immunoprecipitate (125)I-alpha-dendrotoxin-labelled voltage-gated potassium channels extracted from mammalian brain tissue have been identified in patients with neuromyotonia, Morvan's syndrome, limbic encephalitis and a few cases of adult-onset epilepsy. These conditions often improve following immunomodulatory therapies. However, the proportions of the different syndromes, the numbers with associated tumours and the relationships with potassium channel subunit antibody specificities have been unclear. We documented the clinical phenotype and tumour associations in 96 potassium channel antibody positive patients (titres >400 pM). Five had thymomas and one had an endometrial adenocarcinoma. To define the antibody specificities, we looked for binding of serum antibodies and their effects on potassium channel currents using human embryonic kidney cells expressing the potassium channel subunits. Surprisingly, only three of the patients had antibodies directed against the potassium channel subunits. By contrast, we found antibodies to three proteins that are complexed with (125)I-alpha-dendrotoxin-labelled potassium channels in brain extracts: (i) contactin-associated protein-2 that is localized at the juxtaparanodes in myelinated axons; (ii) leucine-rich, glioma inactivated 1 protein that is most strongly expressed in the hippocampus; and (iii) Tag-1/contactin-2 that associates with contactin-associated protein-2. Antibodies to Kv1 subunits were found in three sera, to contactin-associated protein-2 in 19 sera, to leucine-rich, glioma inactivated 1 protein in 55 sera and to contactin-2 in five sera, four of which were also positive for the other antibodies. The remaining 18 sera were negative for potassium channel subunits and associated proteins by the methods employed. Of the 19 patients with contactin-associated protein-antibody-2, 10 had neuromyotonia or Morvan's syndrome, compared with only 3 of the 55 leucine-rich, glioma inactivated 1 protein-antibody positive patients (P < 0.0001), who predominantly had limbic encephalitis. The responses to immunomodulatory therapies, defined by changes in modified Rankin scores, were good except in the patients with tumours, who all had contactin-associated-2 protein antibodies. This study confirms that the majority of patients with high potassium channel antibodies have limbic encephalitis without tumours. The identification of leucine-rich, glioma inactivated 1 protein and contactin-associated protein-2 as the major targets of potassium channel antibodies, and their associations with different clinical features, begins to explain the diversity of these syndromes; furthermore, detection of contactin-associated protein-2 antibodies should help identify the risk of an underlying tumour and a poor prognosis in future patients.

Epilepsy remains misunderstood, particularly in resource poor countries (RPC). We developed and validated a tool to assess beliefs and attitudes about epilepsy among people with epilepsy (PWE) in Kilifi, Kenya. The 50-item scale was developed through a literature review and qualitative study findings, and its reliability and validity were assessed with 673 PWE. A final scale of 34 items had Cronbach's alpha scores for the five subscales: causes of epilepsy (α=0.71); biomedical treatment of epilepsy (α=0.70); cultural treatment of epilepsy (α=0.75); risk and safety concerns about epilepsy (α=0.56); and negative attitudes about epilepsy (α=0.76) and entire scale (α=0.70). Test-retest reliability was acceptable for all the subscales. The Kilifi Epilepsy Beliefs and Attitude Scale is a reliable and valid tool that measures beliefs and attitudes about epilepsy. It may be useful in other RPC or as a tool to assess the effectiveness of interventions to improve knowledge, beliefs, and attitudes about epilepsy.