Cognitive and motor performance in Congolese children with konzo during 4 years of follow-up: a longitudinal analysis

Background Konzo is an irreversible upper-motor neuron disorder affecting children dependent on bitter cassava for food. The neurocognitive ability of children with konzo over time has yet to be fully documented. Methods We did a longitudinal study in a konzo outbreak zone continuously affected by konzo since 1990, in the district of Kahemba, southern Bandundu Province, Congo. We enrolled children with a record of neurological diagnosis of konzo in Kahemba town. For all study children with konzo enrolled in the final sample for the baseline assessment, a neurological exam was done by neurologists to confirm konzo diagnosis using the 1996 WHO criteria at 2 years and 4 years. In the initial baseline sample for each child with konzo, we attempted to get consent from a comparison child without konzo (1996 WHO criteria) within 2 years of age, from a neighbouring household who met inclusion criteria. The neuropsychological assessments were the Kaufman Assessment Battery for Children, second edition (KABC-II), and the Bruininks-Oseretsky Test of Motor Proficiency, second edition (BOT-2). Findings Data collection occurred between Oct 12, 2011, and Aug 14, 2015, in the town of Kahemba. 123 children from the Congo with konzo and 87 presumably healthy children without konzo from neighbouring households were enrolled. The planned assessments were completed by 76 children with konzo and 82 children without konzo at 2-year follow-up, and by 55 children with konzo and 33 children without konzo at 4-year follow-up. Boys with konzo did worse than those without konzo on the KABC-II Learning (p=0·0424) and on the Mental Processing Index (MPI; p=0·0111) assessments at 2-year follow-up, but girls did not. These differences observed in boys might have been caused by stunting. At 4-year follow-up, the difference in KABC-II MPI score between boys or girls with or without konzo was not significant. Both boys and girls with konzo had lower scores on BOT-2 than children without konzo at both follow-up times (p<0·0001). These differences were not attenuated when controlling for physical growth. Boys with and without konzo declined on BOT-2 fine motor proficiency at 2-year follow-up (boys with konzo p=0·0076; boys without konzo p=0·0224) and KABC-II MPI performance at 2-year follow-up and 4-year follow-up (2 years: boys with konzo p<0·0001, boys without konzo p=0·0213; 4 years: boys with konzo p=0·0256, boys without konzo p=0·10), but that was not the case for the girls with scores remaining stable regardless of konzo status. For boys, increases in urinary thiocyanate concentration was significantly associated with reductions in BOT-2 motor proficiency (p=0·0321), but was not significantly associated in girls and urinary thiocyanate concentration was not associated with KABC-II MPI score for either boys or girls. Interpretation Motor and cognitive performance continues to be significantly impaired in boys with konzo at 2-year follow-up compared with boys without konzo. Because these impairments are associated in part with exposure to poorly processed cassava as measured by urinary thiocyanate, interventions are urgently needed to ensure improved processing of cassava to detoxify this food source

Indice global des signes neurologiques du konzo: marqueur clinique de multiples facteurs de susceptibilite et de gravite des troubles neurocognitifs chez l’enfant en milieu Konzo

Objectif : Quantifier la détérioration neurologique observée dans le konzo eu égard aux multiples déficiences incriminées dans sa pathogénie. Méthodes : Une étude transversale a été entreprise auprès de 123 enfants konzo et 87 non-konzo (4-17 ans) en 2011 à Kahemba, Congo-Kinshasa. L’indice global de signes neurologiques du konzo (IGSNK) était étudié en relation avec le niveau socio-économique familial évalué par le HOME, les performances cognitives au KABC-II et motrices au BOT-2, les taux sériques des isoprostanes, oligoéléments, et l’albuminémie et triglyceridémie mesurés respectivement par LC-MS/MS, ICP-MS, et automate Piccolo. Les tests de χ2, de Mann-Whitney et Kruskal-Wallis, ou la corrélation r de Spearman ont été appliqués au seuil de signification de 0,05. Résultats : L’augmentation de l’indice global des signes neurologiques du konzo était associée à la sévérité de la maladie (p &lt; 0,001), le niveau socioéconomique familial (r = – 0,25 ; p &lt; 0,001, la triglyceridémie (r = 0,55 , p = 0,001) et les 8,12-IsoProstaneF2-VI sériques (r = 0,33 , p= 0,06),), l’albuminémie (r = – 0,44 , p = 0,010 ) , la cuprémie ( r = – 0,36 , p= 0,048), le sélenium sérique (r = – 0,57, p = 0,001) ; en plus de l’habilité motrice globale (r = -0,861 ; p &lt; 0,001) et l’indice global de fonctionnement cognitif (r = – 0,44 ; p = 0,002).Conclusion : L’indice global des signes neurologiques du konzo paraît être un bon marqueur clinique de multiples déficiences (pauvreté socio-familiale, malnutrition, stress oxydatif) incriminées dans la sévérité du konzo.Mots clés: malnutrition, niveau socio-économique familial, stress oxydatif, konzo, intoxication cyanhydrique, troubles moteurs et cognitifs  Konzo global neurological index: a clinical marker of susceptibility and severity of neurocognitive deficits in children living in Konzo-affected areasObjective: To quantify the extent of neurological deficits in konzo in a context of multiple factors incriminated in its pathogenesis. Methods: A cross-sectional study was carried out to assess 123 children with and 87 presumably healthy controls (4-17 years) in 2011 in kahemba, congo-kinshasa. A konzo global neurological index (KGNI) was constructed and assessed in relation to socio-economic status (assessed using the home questionnaire),  cognitive and motor performances at the KABC-II and BOT-2, respectively; serum isoprostanes (measured by LC/MS-MS), trace elements (by ICP-MS), albumin and triglycerides (by automated Piccolo). The chi-square, Mann-Whitney and Kruskal-Wallis tests as well as the Spearman r coefficients were used at the 0.05 level of statistical significance.Results: A higher KGNI was significantly associated with the severity of konzo (p &lt; 0.001), poor socio-economic status (r = – 0.25, p &lt; 0.001), elevated serum triglycerides (r = 0.55, p = 0.001), 8,12-isoprostane F2-VI (r = 0.33, p = 0.06), hypoalbuminemia (r = – 0.44, p = 0.010), low serum concentrations copper (r = – 0.36, p = 0.048) or selenium (r = – 0.57, p = 0.001);in addition to poor scores at the BOT-2 testing (r = -0.86; p &lt; 0.001) and KABC-II testing for cognition (r = – 0.44; p = 0.002).Conclusion: The konzo global neurological index appears to be a good clinical marker of disease susceptibility factors (poor socio-economic status, malnutrition, oxidative stress) incriminated in the severity of konzo.Key words: malnutrition, socio-economic status, oxidative stress, cyanide intoxication, neurocognitio

Troubles socio-émotionnels de l’enfant en milieu Konzo, un syndrome paralytique de nature épidémique associé à une intoxication cyanhydrique d’origine alimentaire en Afrique sub-saharienne

Introduction:&nbsp;l’objectif de cette étude était d’élucider le profil socio-émotionnel de l’enfant en milieu Konzo, une paralysie toxico-nutritionnelle sévissant en Afrique sub-saharienne. Méthodes:&nbsp;nous avons évalué le profil socio-émotionnel de 210 enfants dont 123 avec konzo et 87 présumés contrôles sains (4-17 ans d’âge) après interview structuré avec les parents lors d’une enquête épidémio-clinique du konzo en 2011 au Congo-Kinshasa. Le profil neurocognitif était documenté par le KABC-II, le BOT-2 et l’indice global des signes neurologiques du Konzo (IGSNK). Les tests associatifs ont été réalisés par le test de Chi-carré, la régression logistique, dans le cas échéant par modèle linéaire généralisé, au seuil de signification de 0,05. Résultats:&nbsp;dans l’ensemble, l’irritabilité, la violence physique ou l’inhibition avec ou sans tristesse étaient respectivement retrouvés dans 46,0%, 30,2%, 18,7%; avec un risque accru pour le Konzo (OR = 2,6; IC95%: 1,4 - 4,8; p = 0,001). Le trouble socio-émotionnel était associé à l’insuffisance pondérale (OR: 0,49; IC95%: 0,31 - 0,78; p = 0,002) et à un IGSNK élevé (OR: 1,33; IC 95%: 1,1-1,63; p=0,019); et par ailleurs aggravait les déficits cognitifs dans le Konzo (interaction statut neurologique χ troubles socio-émotionnels, D = 6,297; p = 0,013). Des performances cognitives élevées étaient observées chez les enfants non-Konzo mais avec troubles socio-émotionnels. La concentration moyenne (écart-type ± ET) de thiocyanate urinaire était plus élevé (554,8 ± 371,6 µmol/l) chez les enfants Konzo avec troubles socio-émotionnels. Conclusion:&nbsp;l’enfant vivant en milieu Konzo présente des troubles socio-émotionnels. Leur nature psychopathologique et l’impact sur la cognition nécessitent des études approfondies

Lead exposure and early child neurodevelopment among children 12–24 months in Kinshasa, the Democratic Republic of Congo

Childhood lead exposure remains a problem in developing countries, and little is known about its effects on early child neurodevelopment and temperament in the Democratic Republic of Congo (DRC). We, therefore, conducted this study to determine the association between lead exposure and the neurodevelopment and behaviour of children aged 12–24 months in Kinshasa, DRC. A cross-sectional study was conducted between February and June 2012, and parents of 104 children were invited to participate. Blood lead levels (BLLs) of each child were tested using the flame atomic spectrophotometry method. All children were subject to a clinical examination and assessed with two selected early child neurodevelopmental tools, the Gensini–Gavito and the baby characteristics questionnaire, to measure their neurodevelopment and temperament. Detectable BLLs ranged from 1 to 30 μg/dl with a geometric mean of 6.9 (SD 4.8) μg/dl. BLLs at 5–9 and ≥10 μg/dl were significantly associated with the child temperament (p <0.05). Perinatal and maternal factors did not seem to affect early child neurodevelopment and temperament. Children exposed to lead were reported with more temperament difficulties at even blood lead levels <10 μg/dl, suggesting the need for preventive and intervention measures to reduce lead exposure among children in Kinshasa, DRC

Serum 8,12-iso-iPF2α-VI isoprostane marker of oxidative damage and cognition deficits in children with konzo.

We sought to determine whether motor and cognitive deficits associated with cassava (food) cyanogenic poisoning were associated with high concentrations of F2-isoprostanes, well-established indicators of oxidative damage. Concentrations of serum F2-isoprostanes were quantified by LC-MS/MS and anchored to measures of motor proficiency and cognitive performance, which were respectively assessed through BOT-2 (Bruininks/Oseretsky Test, 2nd Edition) and KABC-II (Kaufman Assessment Battery for Children, 2nd edition) testing of 40 Congolese children (21 with konzo and 19 presumably healthy controls, overall mean age (SD): 9.3 (3.2) years). Exposure to cyanide was ascertained by concentrations of its main metabolite thiocyanate (SCN) in plasma and urine. Overall, SCN concentrations ranged from 91 to 325 and 172 to 1032 µmol/l in plasma and urine, respectively. Serum isoprostanes ranged from 0.1 to 0.8 (Isoprostane-III), 0.8 to 8.3 (total Isoprostane-III), 0.1 to 1.5 (Isoprostane-VI), 2.0 to 9.0 (total Isoprostane-VI), or 0.2 to 1.3 ng/ml (8,12-iso-iPF2α-VI isoprostane). Children with konzo poorly performed at the BOT-2 and KABC-II testing relative to presumably healthy children (p<0.01). Within regression models adjusting for age, gender, motor proficiency, and other biochemical variables, 8,12-iso-iPF2α-VI isoprostane was significantly associated with the overall cognitive performance (β = -32.36 (95% CI: -51.59 to -13.03; P<0.001). This model explained over 85% of variation of the KABC-II score in children with konzo, but was not significant in explaining the motor proficiency impairment. These findings suggest that cognitive deficits and, possibly, brain injury associated with cassava poisoning is mediated in part by oxidative damage in children with konzo. 8,12-iso-iPF2α-VI isoprostane appears to be a good marker of the neuropathogenic mechanisms of konzo and may be used to monitor the impact of interventional trials to prevent the neurotoxic effects of cassava cyanogenic poisoning

Dietary cyanogen exposure and early child neurodevelopment: An observational study from the Democratic Republic of Congo

<div><p>Background</p><p>Dietary cyanogen exposure from ingesting bitter (toxic) cassava as a main source of food in sub-Saharan Africa is related to neurological impairments in sub-Saharan Africa. We explored possible association with early child neurodevelopmental outcomes.</p><p>Methods</p><p>We undertook a cross-sectional neurodevelopmental assessment of 12–48 month-old children using the Mullen Scale of Early Learning (MSEL) and the Gensini Gavito Scale (GGS). We used the Hopkins Symptoms Checklist-10 (HSCL-10) and Goldberg Depression Anxiety Scale (GDAS) to screen for symptoms of maternal depression-anxiety. We used the cyanogen content in household cassava flour and urinary thiocyanate (SCN) as biomarkers of dietary cyanogen exposure. We employed multivariable generalized linear models (GLM) with Gamma link function to determine predictors of early child neurodevelopmental outcomes.</p><p>Results</p><p>The mean (<i>SD</i>) and median (IQR) of cyanogen content of cassava household flour were above the WHO cut-off points of 10 ppm (52.18 [32·79]) and 50 (30–50) ppm, respectively. Mean (<i>SD</i>) urinary levels of thiocyanate and median (IQR) were respectively 817·81 (474·59) and 688 (344–1032) μmole/l in mothers, and 617·49 (449·48) and 688 (344–688) μmole/l in children reflecting individual high levels as well as a community-wide cyanogenic exposure. The concentration of cyanide in cassava flour was significantly associated with early child neurodevelopment, motor development and cognitive ability as indicated by univariable linear regression (<i>p</i> < 0.05). After adjusting for biological and socioeconomic predictors at multivariable analyses, fine motor proficiency and child neurodevelopment remained the main predictors associated with the concentration of cyanide in cassava flour: coefficients of -0·08 to -.15 (<i>p</i> < 0·01). We also found a significant association between child linear growth, early child neurodevelopment, cognitive ability and motor development at both univariable and multivariable linear regression analyses coefficients of 1.44 to 7.31 (<i>p</i> < 0·01).</p><p>Conclusion</p><p>Dietary cyanogen exposure is associated with early child neurodevelopment, cognitive abilities and motor development, even in the absence of clinically evident paralysis. There is a need for community-wide interventions for better cassava processing practices for detoxification, improved nutrition, and neuro-rehabilitation, all of which are essential for optimal development in exposed children.</p></div

Proportion of different factors related to the child’s medical and perinatal history, parental level of education, stimulation & learning opportunities for the 114 studied children aged 12–48 months in Kahemba, Democratic Republic of Congo.

<p>Proportion of different factors related to the child’s medical and perinatal history, parental level of education, stimulation & learning opportunities for the 114 studied children aged 12–48 months in Kahemba, Democratic Republic of Congo.</p

Overall and by household groups crude coefficient (<i>p</i>-value) from the univariable linear regression for scores derived from Mullen Scale of Early Learning, Gensini Gavito Scale, and cassava cyanogen content for the 114 studied children aged 12–48 months in Kahemba, democratic republic of Congo.

<p>Overall and by household groups crude coefficient (<i>p</i>-value) from the univariable linear regression for scores derived from Mullen Scale of Early Learning, Gensini Gavito Scale, and cassava cyanogen content for the 114 studied children aged 12–48 months in Kahemba, democratic republic of Congo.</p

Mullen Scale for Early Learning and Gensini Gavito Scale scores of the 114 studied children aged 12–48 months old in Kahemba, Democratic Republic of Congo.

<p>Mullen Scale for Early Learning and Gensini Gavito Scale scores of the 114 studied children aged 12–48 months old in Kahemba, Democratic Republic of Congo.</p