Effect of ethanolic extract of Coriandrum sativum L. on tacrine induced orofacial dyskinesia.

The effect of ethanolic extract of Coriandrum sativum L. seeds (100, 200 mg/kg) was studied on tacrine induced orofacial dyskinesia. Tacrine (2.5 mg/kg, i.p.) treated animals were observed for vacuous chewing movements (VCM), tongue protrusions (TP) and orofacial bursts (OB) for 1 h followed by observations for locomotor changes and cognitive dysfunction. Sub-chronic administration of Coriandrum sativum L. seed extract (E-CS) (100, 200 mg/kg, p.o., for 15 days significantly (P <0.05) decreased the tacrine induced VCM, TP and OB; and also significantly (P <0.05), increased locomotion and cognition compared to the tacrine treated group. Biochemical analysis revealed that tacrine administration significantly (P <0.05) decreased the levels of superoxide dismutase (SOD), Catalase (CAT), glutathione reductase (GSH) levels and also significantly (P <0.05) increased lipid peroxidation (LPO) as an index of oxidative stress, whereas sub-chronic administration of E-CS significantly (P <0.05) improved the antioxidant enzyme (i.e. SOD, CAT, and GSH) levels and also significantly (P <0.05) decreased lipid peroxidation (LPO). The results have demonstrated the protective role of ethanolic extract of Coriandrum sativum. L against tacrine induced orofacial dyskinesia.

Cognitive Dysfunction in Drug-induced Parkinsonism Caused by Prokinetics and Antiemetics

The use of prokinetics/antiemetics is one of the leading causes of drug-induced parkinsonism (DIP) observed in neurology clinics. Cognitive dysfunction in DIP has recently been recognized, but pathologies related with cognitive dysfunction is unknown. Among our retrospective cohort of 385 consecutive parkinsonian patients enrolled in our parkinsonism registry, 14 patients were identified who satisfied our inclusion criteria: parkinsonism caused by prokinetics/antiemetics, existing T1-weighted 3D volumetric MR images, and normal [18F]-N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane PET scan images. For the comparison of volumetric MR data, 30 age- and sex-matched healthy individuals were included in this study. Among 14 patients with DIP, 4 patients were diagnosed with dementia, and all other patients had mild cognitive impairment (MCI). Comparisons of MR volumetric data between DIP patients with MCI and controls show that cortical gray matter volumes are reduced bilaterally in DIP (P=0.041) without changes in either total white matter volume or total intracranial volume. Among subcortical structures, the volume of the right hippocampus is reduced in DIP patients compared with controls (P=0.011, uncorrected). In DIP, cortical thickness is reduced in the bilateral lingual (P=0.002), right fusiform (P=0.032) and part of the left lateral occipital gyri (P=0.007). Our results suggests that cognitive dysfunction in DIP caused by prokinetics/antiemetics is common. Structural changes in the brain by 3D MRI may be associated with cognitive decline in DIP.

Cannabinoides: un obstáculo cognitivo para conducir con seguridad / Cannabinoids: a cognitive obstacle to drive safely

Las altas pérdidas económicas y humanas que traen consigo los accidentes de tránsito, además de sus implicaciones sociales y políticas, hacen evidente la necesidad de una comprensión clara de todos los factores que modifican su incidencia y severidad, entre los cuales se enuncia el consumo de psicotrópicos como el cannabis. Tras dos décadas de reducciones sustanciales en la magnitud del problema de la ingesta de alcohol y accidentes de tránsito, el uso extendido de cannabis en todo el mundo es lo que la hace, después del alcohol, la sustancia psicotrópica más frecuentemente hallada en la sangre de los conductores implicados en este tipo de accidentes; la presencia de cannabis se asocia con el doble de riesgo de ser herido fatalmente en el tráfico. Contrario a la creencia general, la marihuana no debe ser considerada una droga benigna; su consumo se asocia con trastornos cardiovasculares, pulmonares, reproductivos, inmunológicos y sobretodo sobre el sistema locomotor y cognitivo; concentraciones de tetrahidrocannabinol en sangre de 2 a 5 ng/mL, se asocian con deterioro sustancial en las habilidades necesarias para operar un vehículo motorizado. Por esta razón, se requieren aún más investigaciones que establezcan nexos claros de causalidad, y que permitan generar a largo plazo políticas públicas de responsabilidad vial que divulguen las devastadoras repercusiones humanas, sociales y económicas que genera el hecho de consumir cannabis y operar un vehículo motorizado en la vía.

The high economic and human losses that bring traffic accidents, as well as their social and political implications, make evident the need of a clear understanding of all the factors that influence its incidence and severity, between which states the use of psychotropic drugs as cannabis. After two decades of substantial reductions in the magnitude of the problem of alcohol consumption and traffic accidents, the widespread use of cannabis in the world is what makes it, after alcohol, the psychoactive substance most commonly found in the blood of drivers involved in such accidents; the presence of cannabis is associated with twice the risk of being fatally injured in traffic. Contrary to popular belief, marijuana should not be considered a benign drug, its use is associated with cardiovascular, pulmonary, reproductive, immunological, and especially with locomotor and cognitive disorders; blood tetrahydrocannabinol concentrations of 2-5 ng/mL are associated with substantial deterioration in the skills needed to operate a motor vehicle. Therefore, further investigations are required to establish clear causal links, to favor the generation of long-term public policy of vial responsibility, to divulge the devastating human, social and economic impacts that are generated because of the act of consuming cannabis while operating a motor vehicle on the track.

Agmatine Improves Cognitive Dysfunction and Prevents Cell Death in a Streptozotocin-Induced Alzheimer Rat Model

PURPOSE: Alzheimer's disease (AD) results in memory impairment and neuronal cell death in the brain. Previous studies demonstrated that intracerebroventricular administration of streptozotocin (STZ) induces pathological and behavioral alterations similar to those observed in AD. Agmatine (Agm) has been shown to exert neuroprotective effects in central nervous system disorders. In this study, we investigated whether Agm treatment could attenuate apoptosis and improve cognitive decline in a STZ-induced Alzheimer rat model. MATERIALS AND METHODS: We studied the effect of Agm on AD pathology using a STZ-induced Alzheimer rat model. For each experiment, rats were given anesthesia (chloral hydrate 300 mg/kg, ip), followed by a single injection of STZ (1.5 mg/kg) bilaterally into each lateral ventricle (5 microL/ventricle). Rats were injected with Agm (100 mg/kg) daily up to two weeks from the surgery day. RESULTS: Agm suppressed the accumulation of amyloid beta and enhanced insulin signal transduction in STZ-induced Alzheimer rats [experimetal control (EC) group]. Upon evaluation of cognitive function by Morris water maze testing, significant improvement of learning and memory dysfunction in the STZ-Agm group was observed compared with the EC group. Western blot results revealed significant attenuation of the protein expressions of cleaved caspase-3 and Bax, as well as increases in the protein expressions of Bcl2, PI3K, Nrf2, and gamma-glutamyl cysteine synthetase, in the STZ-Agm group. CONCLUSION: Our results showed that Agm is involved in the activation of antioxidant signaling pathways and activation of insulin signal transduction. Accordingly, Agm may be a promising therapeutic agent for improving cognitive decline and attenuating apoptosis in AD.

Neurobiological effect of 7-nitroindazole, a neuronal nitric oxide synthase inhibitor, in experimental paradigm of Alzheimer’s disease.

Nitric oxide plays a role in a series of neurobiological functions, underlying behaviour and memory. The functional role of nNOS derived nitric oxide in cognitive functions is elusive. The present study was designed to investigate the effect of specific neuronal nitric oxide synthase inhibitor, 7-nitroindazole, against intracerebroventricular streptozotocin-induced cognitive impairment in rats. Learning and memory behaviour was assessed using Morris water maze and elevated plus maze. 7-nitroindazole (25 mg/kg, ip) was administered as prophylactically (30 min before intracerebroventricular streptozotocin injection on day 1) and therapeutically (30 min before the assessment of memory by Morris water maze on day 15). Intracerebroventricular streptozotocin produced significant cognitive deficits coupled with alterations in biochemical indices.These behavioural and biochemical changes were significantly prevented by prophylactic treatment of 7-nitroindazole. However, therapeutic intervention of 7-nitroindazole did not show any significant reversal. The results suggests that 7-nitroindazole can be effective in the protection of dementiainduced by intracerebroventricular streptozotocin only when given prophylactically but not therapeutically.

Disfunción neurocognitiva en niños con leucemia linfoide aguda / Neurocognitive disfunction in children with acute lymphoid leukemia

Introducción: se ha comunicado afectación neurocognitiva como secuela a largo plazo en pacientes curados de leucemia linfoide aguda que fueron irradiados durante el tratamiento. Más recientemente esto se plantea también para los tratados solo con quimioterapia. Sobre estos últimos no se conocen antecedentes en Cuba de estudios de este tipo. Métodos: se estudió el rendimiento intelectual de 77 pacientes entre 6 y 32 años (54 con tratamiento y 23 con sobrevida de más de 5 años) que no recibieron radiaciones durante su tratamiento, y de un grupo (n=20) de adolescentes sanos. Se utilizó la escala de inteligencia de Wechsler para niños (Wisc) y para adultos (Wais). Resultados: los resultados mostraron que las escalas totales, tanto de los enfermos como de los curados, se encontraba dentro de parámetros normales. Sin embargo, se obtuvieron notaciones significativamente más bajas en los pacientes curados que en los sanos en las pruebas de semejanzas, dígitos, ordenar figuras y diseño de bloques; también en el factor de distractibilidad. Los pacientes que se encontraban enfermos en la evaluación obtuvieron puntuación más baja que los normales solo en la prueba de dígitos. Conclusiones: estos resultados sugieren afectaciones subclínicas específicas relacionadas con la capacidad de asociación de conceptos verbales, memoria inmediata, capacidad de planeamiento estratégico, organización visoespacial, análisis y síntesis como procesos del pensamiento, así como una dificultad atencional en los pacientes curados como secuela de la quimioterapia

Introduction: neurocognitive disorders have been reported as long-term side effects in patients free from acute lymphoid leukemia that had undergone radiotherapy. These disorders have been likewise reported in those cases in which the patients had undergone chemotherapy. No antecedents about previous study on the latter in Cuba are known. Methods: the intellectual performance of 77 patients who did not undergo radiotherapy during their treatment, ages between 6 and 32 years old, was studied (54 of them under treatment and 23 had survived for more than 5 years); and the intellectual performance of a group of healthy teenagers (n=20). The Wechsler intelligence scales for children (WISC) and for adults (WAIS) were used. Results: the results showed that the Intelligence Quotient of the sick patients and of those already recovered was among standard parameters. However, the recovered patients obtained results significantly lower than those of healthy patients in the Similarity, Digit, Figures Arrangement and Design of Blocks subtests, as well as in the distractibility factor. The patients that were ill during the tests obtained lower results than the healthy ones only in the Digit subtest. Conclusions: these results suggest the presence of specific subclinical disorders related to the capacity of associating verbal concepts, short-term memory, capacity of strategic planning, visualspatial organization, analysis and synthesis such as thinking processes as well as an attention difficulty in recovered patients as a result of chemotherapy

Espontánea reversibilidad de un síndrome de parkinson tardío y de alteraciones cognitivas frontales; después de una intoxicación aguda con órganofosforados / Reversible parkinson syndrome and cognitive impairments due organophosphate acute poisoning

Clásicamente, la intoxicación aguda por órganofosforados produce una crisis colinérgica, que con frecuencia es continuada con un cuadro de debilidad muscular, expresión de un síndrome intermedio. La génesis de estos cuadros está relacionada con la inactivación de la acetilcolinesterasa por el insecticida. Mecanismos diferentes darían origen a polineuropatías y síndromes extrapiramidales tardíos. Se describe un paciente intoxicado agudamente con órganofosforados, que desarrolló una florida crisis colinérgica, que requirió ventilación mecánica invasiva. Después de tres semanas, ya recuperado de una neumonía y del síndrome colinérgico, se pudo definir un daño cognitivo de apariencia frontal, y se apreció la progresiva aparición de hipomimia, rigidez generalizada, bradikinesia y temblor, que configuraron un síndrome de Parkinson. Esta condición clínica se mantuvo al menos por dos semanas, siendo seguida de manera espontánea por una progresiva y completa mejoría del cuadro extrapiramidal y cognitivo. La literatura ha reportado, sólo por excepción casos similares, en los que se destacó tanto la aparición tardía del cuadro parkinsoniano, como su completa y espontánea remisión. Aunque la patogenia del cuadro parkinsoniano no está completamente establecida, existen evidencias experimentales que demuestran que los órganofosforados producen modificaciones en el transporte y en la recaptación de la dopamina. En este paciente se confirmó la doble acción patogénica de los órganofosforados, que habiéndose iniciado con un síndrome colinérgico agudo, finalizó con un compromiso dopaminérgico tardío. La completa recuperación de ambos efectos, permite encasillar a estos insecticidas como generadores de alteraciones funcionales, más que de gestores de daños o cambios estructurales.

Acute organophosphate poisoning usually produces a cholinergic crisis followed by muscular weakness or intermediate syndrome. The basis for these clinical manifestations is inactivation of acetylcholinesterase at the nicotinic and muscarinic nerve terminals and junctions. Different mechanism might lead to polyneuropathy and late extrapyramidal syndromes. We report a case of a male patient who ingested organophosphate with suicidal intentions. He developed a typical cholinergic crisis and required invasive mechanical ventilation. Three weeks later, frontal cognitive impairment was noticed and masklike face, generalized rigidity, bradykinesia and tremor progressively developed until a Parkinson syndrome was established. After his clinical condition had remained stable for at least two weeks, overt spontaneous improvement in motor and cognitive functions was observed. Similar reports in literature are infrequent. Although the pathophysiology that underlies extrapyramidal manifestations due organophosphate poisoning remains unclear, experimental evidence demostróte that organophosphate compounds impair dopamine transport and uptake. This case report suggests that organophosphate might act through a double pathogenic action i.e an initial acute cholinergic syndrome and a delayed disfunction in dopaminergic pathways. Complete spontaneous resolution of both effects allow us to classify organophosphate substances as a cause of functional impairment in the basal ganglia.

Anormalidades cognitivas no uso da cannabis / Cognitive abnormalities and cannabis use

OBJETIVO: Evidências de que o uso de cannabis prejudica funções cognitivas em humanos têm-se acumulado nas décadas recentes. O propósito desta revisão é o de atualizar o conhecimento nesta área com novos achados a partir da literatura mais recente. MÉTODO: As buscas na literatura foram realizadas utilizando-se o banco de dados Web of Science até fevereiro de 2010. Foram buscados os termos "cannabi*" ou "marijuana" e "cogniti*" ou "memory" ou "attention" ou "executive function", e os estudos em humanos foram revisados preferencialmente em relação aos estudos em animais. DISCUSSÃO: O uso de cannabis prejudica a memória, a atenção, o controle inibitório, as funções executivas e a tomada de decisões, tanto durante como após o período de intoxicação aguda, persistindo por horas, dias, semanas ou mais após o último uso. Os estudos de desafio farmacológico em humanos estão elucidando a natureza e os substratos neurais das alterações cognitivas associadas a vários canabinoides. O uso pesado ou de longo prazo de cannabis parece resultar em anormalidades cognitivas mais duradouras e possivelmente em alterações cerebrais estruturais. Efeitos cognitivos adversos maiores estão associados ao uso de cannabis quando este começa no início da adolescência. CONCLUSÃO: O sistema canabinoide endógeno está envolvido nos mecanismos de regulação neural que modulam os processos subjacentes a uma gama de funções cognitivas que estão prejudicadas pela cannabis. Os déficits em usuários humanos muito provavelmente refletem, portanto, neuroadaptações e o funcionamento alterado do sistema canabinoide endógeno.

OBJECTIVE: Evidence that cannabis use impairs cognitive function in humans has been accumulating in recent decades. The purpose of this overview is to update knowledge in this area with new findings from the most recent literature. METHOD: Literature searches were conducted using the Web of Science database up to February 2010. The terms searched were: "cannabi*" or "marijuana", and "cogniti*" or "memory" or "attention" or "executive function", and human studies were reviewed preferentially over the animal literature. DISCUSSION: Cannabis use impairs memory, attention, inhibitory control, executive functions and decision making, both during the period of acute intoxication and beyond, persisting for hours, days, weeks or more after the last use of cannabis. Pharmacological challenge studies in humans are elucidating the nature and neural substrates of cognitive changes associated with various cannabinoids. Long-term or heavy cannabis use appears to result in longer-lasting cognitive abnormalities and possibly structural brain alterations. Greater adverse cognitive effects are associated with cannabis use commencing in early adolescence. CONCLUSION: The endogenous cannabinoid system is involved in regulatory neural mechanisms that modulate processes underlying a range of cognitive functions that are impaired by cannabis. Deficits in human users most likely therefore reflect neuroadaptations and altered functioning of the endogenous cannabinoid system.

Propoxur-induced acetylcholine esterase inhibition and impairment of cognitive function: Attenuation by Withania somnifera.

Propoxur (2-isopropoxyphenyl N-methylcarbamate) is widely used as an acaricide in agriculture and public health programs. Studies have shown that sub-chronic exposure to propoxur can cause oxidative stress and immuno-suppression in rats. Carbamates are also known to exhibit inhibitory effect on cholinesterase activity, which is directly related to their cholinergic effects. In the present study, the effect of Withania somnifera (Ashwagandha), a widely used herbal drug possessing anti-stress and immuno-modulatory properties was studied on propoxur-induced acetylcholine esterase inhibition and impairment of cognitive function in rats. Male Wistar rats were divided into four groups. Group I was treated with olive oil and served as control. Group II was administered orally with propoxur (10 mg/kg b.wt.) in olive oil, group III received a combination of propoxur (10 mg/kg b.wt.) and W. somnifera (100 mg/kg b.wt.) suspension and group IV W. somnifera (100 mg/kg b.wt.) only. All animals were treated for 30 days. Cognitive behaviour was assessed by transfer latency using elevated plus maze. Blood and brain acetylcholine esterase (AChE) activity was also assessed. Oral administration of propoxur (10 mg/kg b.wt.) resulted in a significant reduction of brain and blood AChE activity. A significant prolongation of the acquisition as well as retention transfer latency was observed in propoxur-treated rats. Oral treatment of W. somnifera exerts protective effect and attenuates AChE inhibition and cognitive impairment caused by sub-chronic exposure to propoxur.

Efectos clínicos a largo plazo en niños intoxicados con plomo en una región del sur de Chile / Long term consequences among children exposed to lead poisoning

Background: In 1996 there was a massive lead poisoning in a southern rural community in Chile. The contamination source was a mill whose grinding stone was repaired with lead and contaminated the flour. Aim: To assess the presence of sequelae ten years later, among subjects that were exposed to lead on that occasion. Material and methods: Cross sectional study of 77 individuals (47 males), aged 10 to 25 years, that were exposed to lead in 1996 and were treated with EDTA. Results: Twenty one percent of subjects had a subnormal intellingence quotient (IQ). The risk of having a low IQ was significantly higher among those exposed before the age of six years. IQ was significantly lower among subjects that, immediately after the exposure, had a lead level over 48 fig/dl, compared with those that had a lead level below 43 fig/dl (86.7±7.3 and 93±11.6 respectively). No subjects with high blood pressure or evidences of nephrotoxicity were detected. Conclusions: Subjects aged ¡ess than six years at the moment of lead exposure had a lower IQ when assessed ten years later.

Efectos del consumo de marihuana en funciones cognitivas en jóvenes adolescentes / Effects of consumption of marihuana on cognitive functions in young students

El presente estudio explora el efecto de la marihuana en una población de jóvenes adolescentes escolares, que sólo consumen esta droga ilícita y no otra, y que jamás han consultado a un especialista por problemas de adicción. Los resultados muestran el efecto del consumo habitual de marihuana en funciones cognitivas involucradas en el aprendizaje. Una vez identificados los sujetos, se realizan evaluaciones individuales de estudiantes consumidores y no consumidores de educación media de establecimientos de dependencia municipal, particular subvencionada y particular pagada del Area Metropolitana (Santiago de Chile). Se evidencian efectos nocivos sobre la memoria inmediata, atención-concentración y estrategias de ejecución en los consumidores, con diferencias estadísticamente significativas respecto al grupo control. Se constata mayor consumo relativo en colegios pertenecientes a sectores marginales y escasa o inexistente percepción de daño asociado al consumo de la droga, especialmente entre los consumidores habituales. Las niñas tienden a igualar los niveles de consumo de los varones.

This study evaluates the effects of marihuana in a population of 14 to 17 year old secondary school students, who consume exclusively this illegal drug, and who have never consulted a specialist for addiction problems. The results show the effects of habitual consumption of marihuana on cognitive functions involved in the learning process. Once the subjects have been identified, individual evaluations are performed on students who consume and who do not consume marihuana in public, subsidized public, and private schools of Santiago, Chile. Harmful effects are detected on immediate memory, attention-concentration and execution strategies in consumers, with statistically significant differences in comparison to the control group. Higher consumption is found in schools in poorer districts. There is impaired perception of harm associated with the consumption of the drug especially among habitual consumers. Girls tend to consume the same amount as boys.

Opióides e a cognição de doentes com dor crônica: revisão sistemática / Opioids and cognition by patients with chronic pain: a systematic review

OBJETIVO: A crescente utilização de opióides em doentes com dor crônica de etiologias variadas e os possíveis efeitos desses fármacos em atividades diárias suscitam a importância de se avaliar tais efeitos. Com essa finalidade, desenvolveu-se este estudo de revisão sistemática que avaliou a influência de opióides nas funções cognitivas de doentes com dor crônica. MÉTODOS: Onze bases de dados foram analisadas utilizando-se os descritores opioids, opiates, narcotics, cognitive impairment, cognitive dysfunction, cognitive disorders e pain. Os critérios de inclusão foram: ensaios clínicos ou relatos de caso de dor crônica em tratamento com opióides, testes específicos para avaliação cognitiva e publicação em inglês, espanhol ou português. RESULTADOS: Dezesseis pesquisas, publicadas entre 1980 e 2004, atenderam aos critérios: seis ensaios controlados, sendo dois deles randomizados, e dez estudos de menor força de evidência científica. Os ensaios de melhor qualidade, no contexto clínico do doente com dor crônica, principalmente na dor de origem não oncológica, mostraram que o uso de opióides não prejudica a função cognitiva. CONCLUSÃO: A ausência de prejuízo cognitivo com uso de opióides precisa ser confirmada em novos ensaios randomizados com número maior de pacientes com dor crônica.

OBJECTIVE: The increasing use of opioids by patients suffering from chronic pain caused by different etiologies, and the possible effects of those substances on everyday activities, require careful evaluation of their effects. For this purpose, a systematic review was developed to assess the influence of opioids on the cognitive function in patients with chronic pain. METHODS: Eleven databases were analyzed using the following descriptors: opioids, opiates, narcotics, cognitive impairment, cognitive dysfunction, cognitive disorders and pain. The inclusion criteria were: clinical trials or case reports which included patients with chronic pain in treatment with opioids, cognitive assessment by specific tests and publication in English, Spanish or Portuguese. RESULTS: Sixteen surveys published between 1980 and 2004 met the criteria: six controlled trials, two randomized trials, and 10 studies of a lower scientific evidence level. All better quality controlled trials did not show cognitive impairment of patients under opioid therapy. CONCLUSION: These results must be confirmed by additional randomized trials including a greater number of patients with chronic pain.

Alteração na atenção e o tratamento da dor do câncer / Alteration in attention and cancer pain treatment

Os danos à vida diária que a alteração cognitiva pode provocar motivaram a elaboração deste estudo, cujo objetivo foi analisar o impacto do tratamento da dor com opióides sobre a atenção. Os doentes foram divididos em grupos que recebiam (n=14) e não recebiam opióides (n=12). Foram feitas três entrevistas, utilizando-se o Trail Making Test e o Digit Span Test, que avaliam a atenção. Os grupos foram homogêneos nas variáveis sociodemográficas, dor e depressão; não foram homogêneos no índice de Karnofsky e no recebimento de analgésicos adjuvantes. Os doentes sem opióides tiveram melhor desempenho no Digit Span Test - ordem inversa, na segunda avaliação (p=0,29) e não foram observadas diferenças no Trail Making Test. As alterações observadas foram limitadas, mas, enquanto novos estudos não confirmem os achados, doentes, profissionais e cuidadores devem ser alertados dos possíveis efeitos deletérios dos opióides sobre a função cognitiva.

Cognitive impairment can negatively impact daily routine. This fact encouraged the elaboration of this study, which analyzed the impact of pain treatment with opioids on attention. Patients were divided into groups that were given (n=14) and were not given opioids (n=12). Three interviews were conducted to assess attention using the Trail Making Test and the Digit Span Test. The groups were homogeneous regarding socio-demographic variables, pain and depression; they were not homogeneous regarding the Karnofsky scale and the use of adjuvant analgesics. The patients in treatment without opioids had better performance in the Digit Span Test - reverse order, in the second assessment (p=0.29); no differences were observed on the Trail Making Test. The observed impairments were limited, but while new studies do not confirm the findings, patients, professionals and caregivers must be alert about the possible deleterious effects of opioids on the cognitive function.

Los daños a la vida diaria que la alteración cognoscitiva puede causar motivaron la elaboración de este estudio, cuyo objetivo fue analizar el impacto del tratamiento del dolor con los opioides en la atención. Los enfermos fueron divididos en grupos que recibieron (n=14) y no recibieron opioides (n=12). Fueron realizadas tres entrevistas utilizándose el Trail Making Test y el Digit Span Test, que evalúan la atención. Los grupos fueron homogéneos en las variables sociodemográficas, dolor y depresión; no fueron homogéneos en el índice de Karnofsky y en el suministro de analgésicos adyuvantes. Los pacientes sin opioides tuvieron mejor desempeño en el Digit Span Test - reverse order, en la segunda entrevista (p=0,29) y no se observaron diferencias en el Trail Making Test. Las alteraciones observadas fueron limitadas, sin embargo mientras nuevos estudios no confirmen los resultados, pacientes, profesionales y cuidadores deben ser alertados sobre los posibles efectos deletéreos de los opioides en la función cognoscitiva.

Revisão: funcionamento executivo e uso de maconha / Review: executive functioning and cannabis use

OBJETIVO: A maconha é a droga ilícita mais consumida no mundo, porém ainda existem poucos estudos examinando eventuais prejuízos cognitivos relacionados ao seu uso. As manifestações clínicas associadas a esses déficits incluem síndrome amotivacional, prejuízo na flexibilidade cognitiva, desatenção, dificuldade de raciocínio abstrato e formação de conceitos, aspectos intimamente ligados às funções executivas, as quais potencialmente exercem um papel central na dependência de substâncias. O objetivo do estudo foi fazer uma revisão a respeito das implicações do uso da maconha no funcionamento executivo. MÉTODO: Esta revisão foi conduzida utilizando-se bases de dados eletrônicas (MedLine, Pubmed, SciELO and Lilacs). DISCUSSÃO: Em estudos de efeito agudo, doses maiores de tetrahidrocanabinol encontram-se associadas a maior prejuízo no desempenho de usuários leves em tarefas de controle inibitório e planejamento; porém, este efeito dose-resposta não ocorre em usuários crônicos. Embora haja controvérsias no que se refere a efeitos residuais da maconha, déficits persistentes parecem estar presentes após 28 dias de abstinência, ao menos em um subgrupo de usuários crônicos. CONCLUSÕES: Os estudos encontrados não tiveram como objetivo principal a avaliação das funções executivas. A seleção de testes padronizados, desenhos de estudos mais apropriados e o uso concomitante com técnicas de neuroimagem estrutural e funcional podem auxiliar na melhor compreensão das conseqüências deletérias do uso crônico da maconha no funcionamento executivo.

OBJECTIVE: Cannabis is the most used illicit drug worldwide, however only a few studies have examined cognitive deficits related to its use. Clinical manifestations associated with those deficits include amotivational syndrome, impairment in cognitive flexibility, inattention, deficits in abstract reasoning and concept formation, aspects intimately related to the executive functions, which potentially exert a central role in substance dependence. The objective was to make a review about consequences of cannabis use in executive functioning. METHOD: This review was carried out on reports drawn from MedLine, SciELO, and Lilacs. DISCUSSION: In studies investigating acute use effects, higher doses of tetrahydrocannabinol are associated to impairments in performance of nonsevere users in planning and control impulse tasks. However, chronic cannabis users do not show those impairments. Although demonstration of residual effects of cannabis in the executive functioning is controversial, persistent deficits seem to be present at least in a subgroup of chronic users after 28 days of abstinence. CONCLUSIONS: The neuropsychological studies found did not have as a main aim the evaluation of executive functioning. A criterial selection of standardized neuropsychological tests, more appropriate study designs as well as concomitant investigations with structural and functional neuroimaging techniques may improve the understanding of eventual neurotoxicity associated with cannabis use.

Disminución de ácido fólico y alteraciones cognitivas en pacientes con epilepsia tratados con fenitoína o carbamazepina, estudio piloto / Decrease of folic acid and cognitive alterations in patients with epilepsy treated with phenytoin or cartnabazepine, pilot study

Introduction. Phenytoin and carbamazepine were the antiepileptic drugs most frequently used in Mexico and throughout the world. Epileptic patients who take these drugs have a variety of collateral effects including the decrease of Mates plas-matic level. Low serie folie acid concentration has been associated with a decline in cognitive functions. The administration of a combined treatment with folie acid could ameliorate these difficulties. Objective.To describe the effect of the folie acid in the cognitive function in epileptic patients who take phenytoin and carbamazepine. Methods. We chose patient who have epilepsy and that are being treated with phenytoin, carbamazepine or both and formed two groups. The study group was treated with a daily dose of 5 mg of folie acid and the control group was administered placebo for a period of six months, with nine patients in each group of same age, sex, education level, epilepsy's evolution, frequency of seizures, EEG abnormalities and antiepileptic drugs plasma levels. We registered data at the beginning (basal) and at the end of the study. Results.Measurements of basal folie acid plasma levels in both groups were under the referential value. The neuropsychological assessment at the beginning (Mini-Barcelona test) showed a deficit in the verbal memory skills in both groups. After six months of treatment with folie acid (study group), the folie acid plasma level was 12.2 mg/mL (p < 0.01) higher than the basal value. Verbal memory test has improved with respect to the basal value (p < 0.05). The numbers of seizures and the plasma levels of the antiepileptic drugs remained unchanged. On the other hand, the group treated with placebo did not improve. Conclusion.Treatment with folie acid is safe and without side effects, it improved the cognitive function in patients with epilepsy treated with phenytoin and carbamazepine.

Introducción. La difenilhidantoína (DFH) y la carbamazepina (CBZ) son los antiepilépticos más empleados en México y en el mundo, los pacientes con epilepsia que emplean estos fármacos presentan una disminución en las concentraciones séricas de ácido fólico, una de las causas que pueden contribuir a un deterioro cognitivo, por lo que la terapia sustitutiva con ácido fólico pudiera mejorar estas alteraciones. Objetivo. Describir el efecto de la disminución del ácido fólico en la cognición de pacientes con epilepsia tratados con difenilhidantoína y carbamazepina. Material y métodos. Incluimos pacientes tratados con carbamazepina, fenitoína o ambos, con epilepsia. Formamos dos grupos: Un grupo experimental recibió ácido fólico 5 mg/día y otro grupo control recibió placebo durante seis meses, nueve pacientes en cada grupo; pareados en la edad, sexo, escolaridad, tiempo de evolución, námero de crisis, alteraciones EEG, niveles séricos de anticonvulsivos, realizamos estudios neuropsicológicos al inicio (básales) y al final del estudio a ambos grupos. Resultados. Las básales del ácido fólico en ambos grupos estuvieron por debajo del valor de referencias. En las pruebas neuropsicológicas (básales) (prueba de Mini-Barcelona) se halló un déficit en el área de la memoria verbal en ambos grupos. Después de seis meses de tratamiento con ácido fólico (grupo experimental) los niveles de ácido fólico alcanzaron 12.2 ng/mL (p < 0.01) con respecto a su basal; las pruebas de memoria verbal mejoraron con respecto a su basal (p < 0.05); el námero de crisis y los niveles séricos de los anticonvulsivos no se modificaron. El grupo con placebo no presentó ninguna mejoría. Conclusiones. El tratamiento coadyuvante con ácido fólico es seguro, libre de efectos adversos y mejoró las alteraciones cognitivas (memoria verbal) de estos pacientes.