Opsoclonus-myoclonus syndrome caused by organophosphate poisoning.

Opsoclonus-myoclonus syndrome is a combination of involuntary, arrhythmic, conjugate saccadic eye movements with myoclonus. The most common cause in adults is paraneoplastic encephalitis. Rarer causes include infections such as scrub typhus, and toxins such as organophosphates and cocaine. Organophosphates are one of the common poisonings in tropical countries such as India, causing both central and peripheral nervous system manifestations. We describe a middle-aged male farmer with unexplained altered consciousness and respiratory depression. After 2 days, he developed opsoclonus-myoclonus, and then bronchorrhoea and bradycardia, raising suspicion of organophosphate poisoning. After we had identified a very low serum cholinesterase concentration, he disclosed having consumed organophosphates.

Neuroleptic malignant syndrome associated with acute organophosphate poisoning: Case report / Síndrome neuroléptico maligno asociado con intoxicación aguda por un organofosforado: reporte de caso.

Neuroleptic malignant syndrome is a rare and potentially fatal clinical condition frequently associated with the use of antipsychotics. In the literature, there is only one case report associated with the intake of organophosphates. We present the case of a patient who presented with a clinical picture compatible with neuroleptic malignant syndrome, after the ingestion of an organophosphate (chlorpyrifos). A 57-year-old man who consulted for attempted suicide, acute deterioration of consciousness, torpid neurological evolution, and associated autonomic instability associated with rigidity, persistent hyperthermia, and elevated CPK. Bromocriptine treatment was offered, which resolved the clinical picture. The association with the ingestion of an organophosphate was established, and he was discharged without sequelae. The diagnosis of neuroleptic malignant syndrome is clinical and should be considered in any case of exposure to substances that may lead to dysregulation of dopaminergic neurotransmission in order to initiate timely therapy and impact outcomes.

El síndrome neuroléptico maligno es una condición clínica rara y potencialmente letal que frecuentemente se asocia con el uso de antipsicóticos. En la literatura especializada se encontró únicamente un reporte de caso relacionado con la ingestión de organofosforados. Se presenta un paciente con un cuadro clínico correspondiente al síndrome neuroléptico maligno posterior a la ingestión de clorpirifós. Como resultado de un intento de suicidio con el mencionado organofosforado, el hombre de 57 años presentó deterioro agudo del estado de consciencia, evolución neurológica tórpida e inestabilidad autonómica asociada a rigidez e hipertermia persistentes, así como incremento de la creatina-fosfocinasa (creatine phosphokinase, CPK). Se le administró tratamiento con bromocriptina, con lo cual el cuadro clínico remitió, y fue dado de alta sin secuelas. El diagnóstico del síndrome neuroléptico maligno es clínico y debe contemplarse en cualquier caso de exposición a sustancias que puedan resultar en una desregulación de la neurotransmisión dopaminérgica, con el fin de iniciar el tratamiento oportuno y contrarrestar efectivamente los efectos.

Occupational exposure to organophosphate pesticides and hematologic neoplasms: a systematic review. / Exposição ocupacional a agrotóxicos organofosforados e neoplasias hematológicas: uma revisão sistemática.

OBJECTIVE: To update findings of observational analytical studies on the association between occupational exposure to organophosphates and hematologic malignancies. METHODOLOGY: Systematic literature review, including cohort and case-control studies, without limitation of publication time, in Portuguese and English. The articles were traced from June 2017 to July 2019 in PubMed, MEDLINE, LILACS, Web of Science, and Scopus databases. The qualitative bias risk assessment was performed using the Newcastle-Ottawa Scale and the Downs and Black Checklist. Results were presented according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). RESULTS: Seventeen studies evaluated as good/high methodological quality were eligible. Exposure to diazinon (1 cohort), phonophos (1 cohort), dichlorvos, crotoxiphos and famphur (1 case control) was associated with leukemia, while exposure to organophosphate was associated to lymphomas (6 case control); the risk of non-Hodgkin's lymphoma was higher in those exposed to diazinon (1 control case) and malathion (3 control case) than non-exposed ones. Multiple myeloma occurred more commonly in organophosphate exposed than in non-exposed individuals (1 case-control). CONCLUSION: Occupational exposure to organophosphates increases the risk of hematologic malignancies, especially among individuals with longer exposure periods. Worker monitoring and exposure control measures are recommended.

Exposição ocupacional a agrotóxicos organofosforados e neoplasias hematológicas: uma revisão sistemática / Occupational exposure to organophosphate pesticides and hematologic neoplasms: a systematic review

RESUMO: Objetivo: Atualizar achados de estudos observacionais analíticos sobre a associação entre exposição ocupacional a organofosforados e neoplasias hematológicas. Métodos: Revisão sistemática de literatura, incluindo estudos de coorte e caso controle, sem limitação de tempo de publicação, nos idiomas português e inglês. O rastreamento de artigos foi feito no período de junho de 2017 a julho de 2019 nas bases de dados PubMed, MEDLINE, LILACS, Web of Science e Scopus. A avaliação qualitativa de risco de viés foi feita com a Escala Newcastle-Otawa e com o Checklist Downs e Black. Os resultados foram apresentados segundo as recomendações da Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). Resultados: Foram elegíveis 17 estudos avaliados como de boa/alta qualidade metodológica. A exposição a diazinon (um coorte), fonofós (um coorte), diclorvós, crotoxifós e fanfur (um caso controle) associou-se à leucemia, enquanto a exposição a organofosforados associou-se aos linfomas (seis caso controle). O risco de linfoma não-Hodgkin foi maior para os indivíduos expostos a diazinon (um caso controle) e malation (três caso controle), em relação aos não expostos. O mieloma múltiplo ocorreu mais comumente em expostos a organofosforados do que entre os não expostos (um caso controle). Conclusão: A exposição ocupacional a organofosforados aumenta o risco de neoplasias hematológicas, sobretudo entre os indivíduos com maior período de exposição. Medidas de monitoramento de trabalhadores e de controle da exposição são recomendadas.

ABSTRACT: Objective: To update findings of observational analytical studies on the association between occupational exposure to organophosphates and hematologic malignancies. Methodology: Systematic literature review, including cohort and case-control studies, without limitation of publication time, in Portuguese and English. The articles were traced from June 2017 to July 2019 in PubMed, MEDLINE, LILACS, Web of Science, and Scopus databases. The qualitative bias risk assessment was performed using the Newcastle-Ottawa Scale and the Downs and Black Checklist. Results were presented according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). Results: Seventeen studies evaluated as good/high methodological quality were eligible. Exposure to diazinon (1 cohort), phonophos (1 cohort), dichlorvos, crotoxiphos and famphur (1 case control) was associated with leukemia, while exposure to organophosphate was associated to lymphomas (6 case control); the risk of non-Hodgkin's lymphoma was higher in those exposed to diazinon (1 control case) and malathion (3 control case) than non-exposed ones. Multiple myeloma occurred more commonly in organophosphate exposed than in non-exposed individuals (1 case-control). Conclusion: Occupational exposure to organophosphates increases the risk of hematologic malignancies, especially among individuals with longer exposure periods. Worker monitoring and exposure control measures are recommended.

Case Control Study of Impulsivity, Aggression, Pesticide Exposure and Suicide Attempts Using Pesticides among Farmers.

A case-control study was conducted to investigate associations between organophosphate pesticide (OP) exposure, aggression, impulsivity, and attempted suicide. Questionnaires were used to collect information; impulsivity and aggression were measured by the Barratt Impulsivity Scale (BIS) and the Aggression Inventory (AI). A greater number of OP symptoms was associated with an increased odds of a suicide attempt after adjusting for marital status and income (OR = 1.45; CI 1.14-1.86). Attempted suicide was significantly associated with high impulsivity scores (means: 72.4 vs. 60.6, P < 0.0001) and high aggression scores (means: 38.5 vs. 26.1, P < 0.0001). Suicide attempters had a higher number of OP exposure symptoms than controls and scored higher on scales of impulsivity and aggression.

Coronary artery bypass grafting in a patient with organophosphate poisoning.

A 43-year-old male, with no previous history of mental illness, was diagnosed with coronary heart disease, after which he became acutely depressed and attempted suicide by ingesting an organophosphate pesticide. He was admitted to an intensive care unit and treated with pralidoxime, atropine, and oxygen. His coronary occlusion pattern required early coronary artery bypass grafting (CABG) surgery. His family, apprehensive of a repeat suicidal attempt, requested surgery be performed as soon as possible. He recovered well from the OP poisoning and was mentally fit to express informed consent 2 weeks after admission. Seventeen days after poisoning, he underwent coronary artery bypass grafting and recovered uneventfully. Six years later, he remains in excellent health. We report this case because to the best of our knowledge there is no literature regarding CABG performed soon after organophosphate poisoning.

Increased risk of deep vein thrombosis and pulmonary thromboembolism in patients with organophosphate intoxication: a nationwide prospective cohort study.

Organophosphate (OP) poisoning is a critical cause of morbidity and mortality worldwide. We conducted a nationwide longitudinal cohort study to investigate the development of deep vein thrombosis (DVT) and pulmonary thromboembolism (PTE) among patients admitted with OP intoxication.We identified patients with OP intoxication by using the Taiwan National Health Insurance Research Database and enrolled 9223 patients who were hospitalized for OP intoxication between 2000 and 2011. OP intoxication was diagnosed based on a clinical assessment and serum acetylcholinesterase levels at the time of hospital admission. Each patient in the OP intoxication cohort was randomly frequency matched with 4 patients without OP intoxication based on their age, sex, and index year (36,892 patients as control cohort), and all patients were observed from the index date until the appearance of a DVT or a PTE event, or until December 31, 2011. We analyzed the risks of DVT and PTE by using Cox proportional hazards regression models that included the demographic variables of sex, age, and comorbidities (eg, hypertension, diabetes, cerebral vascular disease, heart failure, all cancer types, and lower leg fracture or surgery).The results revealed a significantly increased risk of developing DVT among patients with OP poisoning (adjusted hazard ratio [HR] = 1.55; 95% confidence interval [CI] = 1.03-2.34) but not PTE (adjusted HR = 1.44; 95% CI = 0.83-2.52). Among the patients without comorbidities, the OP poisoning patients compared with controls had a higher adjusted HR of 2.12 (95% CI = 1.21-3.71) for DVT.The results of this nationwide cohort study indicate that the risk of developing DVT is markedly higher in patients with OP intoxication compared with that of the general population.

An uncommon pattern of polyneuropathy induced by lifetime exposures to drift containing organophosphate pesticides.

The natural history of chronic peripheral polyneuropathy following lifetime low-level organophosphate (OP) exposure was investigated. A pilot study (1984-1987) conducted in rural communities in Israel detected subtle reversible in-season changes in nerve conduction patterns of 17 field workers out of 214 residents exposed to seasonal drift containing OP's. We examined 60 individuals (males: 50/60; 83.3%) from the original cohort still residing (more than 40 years) in the same communities. Exposure assessment was based on reports by Israeli institutions and the Bureau of Statistics. Information on personal status, work experience, exposures and symptoms was collected by questionnaires. The nervous system was systematically studied, evaluating cortical upper motor neurons, corticospinal tracts, lower motor neurons and peripheral nerves. Electrophysiological studies included conduction velocities, amplitudes and distal latencies of sensory and motor median, ulnar, tibial and sural nerves; F-waves for proximal nerve functions; thermal and pain thresholds for small thinly-myelinated and non-myelinated fibers; transcranial magnetic stimulation for large fibers. Clinical and electrophysiological features of Carpal Tunnel Syndrome were found in 18% of the subjects, atypically in males only. Fingertips' tingling correlated with both axonal and myelin-dependent parameters (lower wave amplitudes and prolonged latency periods, respectively) in the sensory median nerves bilaterally. OP exposure significantly correlated to prolonged distal latency in the right median sensory nerve (r=0.29; p=0.052; n=45) and lower wave amplitude in the right sural nerve (p=0.031). These findings attest to subtle, predominantly sensory peripheral polyneuropathy following lifetime low-level exposures to drifts containing OP.

Afectación de las funciones cognitivas y motoras en niños residentes de zonas rurales de Jujuy y su relación con plaguicidas inhibidores de la colinesterasa: Un estudio piloto / Impairment of cognitive and motor functions in children from rural areas of Jujuy, and its relationship with cholinesterase inhibitor pesticides: A pilot study

El objetivo de este trabajo fue estudiar el efecto de la exposición a plaguicidas en las funciones cognitivas y motoras de 42 niños de una zona rural con mayor probabilidad de exposición a plaguicidas organofosforados y carbámicos (Yuto, Jujuy). Los resultados de las pruebas realizadas para estudiar el efecto fueron comparados con los resultados obtenidos con 29 niños con menor exposición a plaguicidas (León, Jujuy). A todos los participantes se les realizó historia clínica, evaluación médica, revisión de antecedentes, pruebas neuroconductuales, de motricidad gruesa y equilibrio, y medición de biomarcadores (colinesterasa plasmática y eritrocitaria). Se realizó una historia clínica neurológica estándar con las siguientes pruebas: Subtest de Dígitos y Símbolos, Subtest de Recuerdo de Dígitos, Subtest de Laberinto del WISC-III de Wechsler. En la prueba de Laberintos realizada en el presente estudio se observan diferencias entre las localidades y se comprobó una relación lineal inversa entre los años de residencia y la puntuación de la prueba. Se observó reducción en las actividades de acetilcolinesterasas en los niños pertenecientes a Yuto. No se observó una correlación signifca-tiva entre los niveles de actividad de las enzimas y el rendimiento en la prueba, para ninguna de las dos localidades. Los resultados señalaron la probabilidad de que la exposición crónica a bajas dosis de plaguicidas pudiera estar dañando algunas funciones cognitivas y que esto dependería de la duración de la exposición. Por falta de correlación entre las actividades de las enzimas y los resultados adversos en las pruebas neuroconductuales de motricidad y de equilibrio, no fue evidente una asociación entre ambos.

The aim of this research was to study the effects of these toxics on the cognitive and motor functions of a group of 42 children of a rural town with high percentage of exposure to organophosphate and carbamic pesticide (Yuto) and compare the results with a group of 29 children with low percentage of exposure to pesticides. In both cases a research of the patients history was done, a medical revision and a full checkup including neurobehavioral tests, motor and balance tests and biomarkers levels (plasma pseudocholinesterase and erythrocyte cholinesterase). The behavioral assessment was performed by a standard neurological clinic history, a digital and symbol subtest, a digital memory, a maze test, intelligence test WISC-III of Wechsler and gross motor and balance tests. In the group from Yuto, Pearson correlations were done between the years of residency and the neurobehavioral tests and the linear correlation between the years of residency and the acetylcholinesterase activities. In the maze test results there were differences between the two towns and it was proved an inverse lineal relation between the years of residency and the tests scores. It was also observed a reduction in the acetylcholinesterase activities both erythrocyte and plasma in the children from Yuto. Nevertheless there were not signifcant correlations between the levels of enzyme activities and the performance in the tests for neither of the towns. The results achieved did not point out that chronic exposure to low-dose pesticides can produce cognitive malfunctions, such as psychomotor problems. The lack of correlations between the activities of the acetylcholinesterase enzyme and the negative results of the neurobehavioral motor and balance tests couldn´t be associated.

Changes in male hormone profile after occupational organophosphate exposure. A longitudinal study.

There is a growing concern about the endocrine effects of long-term, low-level exposure to organophosphate (OP) compounds. Studies on experimental animals have found that OP pesticides have an impact on the endocrine system and a few clinical and epidemiological studies have also shown that OPs may affect the male hormone profile, although results are inconsistent. We have evaluated the effect of exposure to OP pesticides, measured through urinary levels of six dialkylphosphate (DAP) metabolites, on male hormone profile in 136 floriculture workers from the State of Mexico and Morelos during two agricultural periods with different degree of pesticide exposure. Generalized estimated equations (GEE) models were developed and adjusted for several potential confounders, including PON1 enzyme activity, as a biomarker of susceptibility, and serum levels of p,p'-DDE, a metabolite of the pesticide DDT widely used in Mexico until 1999 for control of agricultural pests and malaria. Exposure of male floriculture workers to OP pesticides was associated with increased serum levels of follicle-stimulating hormone (FSH) and prolactin and with decreased serum testosterone and inhibin B levels. Among all DAPs tested, only DETP was inversely associated with luteinizing hormone (LH). Estradiol showed a marginally significant positive trend with DEP and DETP derivatives. In conclusion, OP pesticides may have an impact on the endocrine function because of their potential to modify the male hormone profile as a function of the type of pesticide used as well as the magnitude of exposure.

Intoxicación por organofosforados: experiencia institucional / By organophosphate poisoning: institutional experience

Objetivo. Describir las características epidemiológicas así como los síntomas y signos de presentación y su relación con el curso evolutivo de los pacientes que ingresan a la Unidad de Urgencias (UU) del Hospital de Clínicas, La Paz, con intoxicación por organofosforados (OF) y carbamatos (CM), con el objetivo de determinar que factores podrian predecir una evolución hospitalaria complicada. Métodos. Se realizó un estudio de serie de casos con 300 pacientes, en base a criterios predefinidos, durante el periodo del 1 de enero al 31 de diciembre de 2003. Resultados. Todas las intoxicaciones fuerón por vía oral, la mayor parte intencionales (97 por ciento), y en pacientes jóvenes (edad media 23.9 rango 13-62). Las mujeres excedieron en número a los varones en proporción de casi 2:1.Los sintomas más comunes en la presentación fueron el dolor abdominal (83 por ciento), nauseas/vómitos (79 por ciento), miosis (72 por ciento), broncorrea (44 por ciento), diarrea (41 por ciento) y fasciculaciones (31 por ciento). Las complicaciones más frecuentes fueron la aspiración (18 por ciento), el paro cardiorrespiratorio (9 por ciento) y convulsiones (7 por ciento); la mortalidad fue del 6 por ciento. Los tratamientos incluyeron el lavado gástrico en 96 por ciento de pacientes, y atropina (dosis media 7.75 mg por paciente.=7.33mg). El predominio de signos colinérgicos se asocio con una proporción más alta de complicaciones. Aunque casi todas intoxicaciones eran tentativas de suicidio, menos de la mitad de los pacientes recibió apoyo psiquiátrico posterior. Conclusiones. La intoxicación por OF es una causa común de morbilidad y mortalidad autoinfligida entre las personas jóvenes en La Paz, Bolivia. La presencia predominante de signos colinérgicos predice una probabilidad más alta de complicaciones durante la hospitalización.

Objective The objective of this study was to describe the demographics, symptoms and hospital course of patients admitted to the Emergency Department (ED) of the Hospital de Clinicas, La Paz, Bolivia with organophosphate (OP) intoxication, with the aim of determining which factors might predict a complicated hospital course. METHODSThis was a retrospective chart review using predefined criteria of 300 patients, who were admitted between Jan. 1, 2003 and Dec. 31, 2003. RESULTSThe intoxications were all oral ingestion, mostly intentional (97%), and in young patients (mean age 23.9, range 13-62). Females outnumbered males almost 2:1. The most common symptoms on admission were abdominal pain (83%), nausea/vomiting (79%), miosis (72%), bronchorrhea (44%), diarrhea (41%) and fasciculations (31%). The most frequent complications were aspiration (18%), cardiopulmonary arrest (9%) and seizure (7%); mortality was 6%. Treatments included gastric lavage in 96% of patients, and atropine (mean dose 7.75mg per patient, σ = 7.33mg). A predominance of cholinergic symptoms at admission was associated with a higher rate of complications. Although almost all intoxications were suicide attempts, less than half of patients received psychiatric consultation. CONCLUSIONSOP intoxication is a common cause of self-inflicted morbidity and mortality among young people in La Paz, Bolivia. Presence of predominantly cholinergic...