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

Konzo and dietary pattern in cassava-consuming populations of Popokabaka, Democratic Republic of Congo

Food frequencies and 24h diet recall were registered from 487 randomly selected heads of household in Popokabaka (Bandundu Province, DRC) where the first cases of konzo were reported more than seventy years ago. Konzo is still occurring in this area with a prevalence of 1.4%.. High prevalence of konzo was found to be associated with female gender (P = 0.0024), unmarried status (P = 0.030), illiteracy (P = 0.021), farmer as main occupation (P< 0.05) and with consumption of cassava from own farm land (P = 0.045). The diet was largely dominated by cassava. Luku, cassava flour stiff porridge, was consumed at least once during the day in 99.2% of households. A median of 304 g (max 592 g; min 120 g) of cassava flour providing 1070 Kcal (max 2085 Kcal; Min 422 Kcal)/ day/person was used to prepare luku. Saka-saka (pounded cassava leaves) (40%), cowpeas (30%), sesame (23.2%), mbondi (Salacia pynaertii) (18.1%), mushrooms (17.7%) and mfumbwa (Gnetum Africanum) (11.3%) were consumed as side-dishes with luku. These results showed that major foods consumed are of poor quality in protein, especially in sulphur containing amino acids

Neuroepidemiology of Konzo a Spastic Para-Tetraparesis of Acute Onset in a New Area of the Democratic Republic of Congo (English)

Background Konzo is an acute non-progressive spastic paraparesis associated with a consumption of insufficiently processed bitter cassava, and a low intake of sulfur amino acids. Method To determine whether an outbreak of spastic paraparesis in the Democratic Republic of Congo was compatible with konzo, we surveyed and screened the population in the affected area by using the WHO criteria. Interviews and focus group discussions were done on diet and the occurrence of konzo. Serum samples were analyzed for prealbumin, albumin and thiocyanate; urine samples for linamarin, thiocyanate and sulfate. Serum samples were tested for HIV1-2 (Behring ELISA) and HTLV I-II antibodies (ELISA/Wellcome). Results Of 2,723 inhabitants, 55 were affected by konzo i.e. a prevalence of 20 per thousand. The main symptom was a sudden onset of a non-progressive spastic paraparesis or a tetraparesis in severe cases. Bitter cassava was the staple diet. We found high exposure to cyanogenic compounds i.e., mean (± SD) concentration of serum thiocyanate 502 (±153) mmol/L, of urinary linamarin 482 (±322) mmol/L, and urinary thiocyanate 1128 (±670) mmol/L. The mean (± SD) urinary sulfate concentration was 4.0 ± 3.3 mmol/L. Most subjects had low proteins concentration in serum: of 38 subjects 37 and 28 were below the albumin and prealbumin reference values respectively. All 38 blood samples were negative to the tested retroviruses. Conclusion This outbreak was compatible with konzo. Improving cassava processing might prevent the disease. Résumé  Description Le Konzo est une paraparésie spastique permanente, à début brutal, associée à la consommation de manioc insuffisamment traité avec une alimentation pauvre en acides aminés soufrés. Objectif Déterminer si une épidémie de paraparésie spastique en République Démocratique du Congo était compatible avec le konzo. Methode Un dépistage des cas de konzo a été effectué au moyen des critères de l\' OMS. Des interviews ont été réalisées sur l\'alimentation et la maladie. Les taux sériques de préalbumine, albumine et thiocyanate furent mesurés ainsi que ceux de linamarine, thiocyanate et sulfate dans les urines. Les serums furent testés pour HIV 1-2 (Behring ELISA) et HTLV I-II (ELISA/Wellcome). Resultats Sur 2.723 habitants, 55 étaient affectés par le konzo, soit une prévalence de 20 pour mille. Le symptôme majeur était une paraparésie spastique permanente à début brutal ou une tétraparésie dans les cas sévères, le manioc amer était l\'aliment de base. Il y avait une importante exposition aux substances cyanogénétiques: concentration moyenne (± écart-type) de thiocyanate sérique 502 (±153) mmol/L, de linamarine urinaire 482 (±322) mmol/L, de thiocyanate urinaire 1128 (±670) mmol/L. La concentration moyenne (± écart-type) de sulfate urinaire était 4.0 ± 3.3 mmol/L. En majorité, le taux des protéines sériques était en dessous de la normale: sur 38 sujets, 37 et 28 l\'avait pour l\'albumine et la préalbumine respectivement. Tous les 38 serums collectés étaient négatifs aux rétrovirus testés. Conclusion Cette épidémie était compatible avec le konzo. Ameliorer le traitement du manioc peut prevenir la maladie. Keywords: acute spastic paraparesis, cassava, cyanogens exposure, konzo, manioc, konzo, paraparésie spastique aigue, substances cyanogènes Af J Neuro Sci: 2001 20(1