Behavioral, affective, and cognitive alterations induced by individual and combined environmental stressors in rats

Objective: To evaluate whether exposing rats to individual or combined environmental stressors triggers endophenotypes related to mood and anxiety disorders, and whether this effect depends on the nature of the behavior (i.e., innate or learned). Methods: We conducted a three-phase experimental protocol. In phase I (baseline), animals subjected to mixed schedule of reinforcement were trained to press a lever with a fixed interval of 1 minute and a limited hold of 3 seconds. On the last day of phase I, an open-field test was performed and the animals were divided into four experimental groups (n=8/group). In phase II (repeated stress), each group was exposed to either hot air blast (HAB), paradoxical sleep deprivation (PSD) or both (HAB+PSD group) on alternate days over a 10-day period. Control group animals were not exposed to stressors. In phase III (post-stress evaluation), behavior was analyzed on the first (short-term effects), third (mid-term effects), and fifth (long-term effects) days after repeated stress. Results: The PSD group presented operant hyperactivity, the HAB group presented spontaneous hypoactivity and anxiety, and the HAB+PSD group presented spontaneous hyperactivity, operant hypoactivity, impulsivity, loss of interest, and cognitive impairment. Conclusion: A combination of environmental stressors (HAB and PSD) may induce endophenotypes related to bipolar disorder.

Diferenciación clínica del déficit cognitivo del CADASIL con respecto a otras demencias vasculares / Clinical differentiation of the cognitive deficit of CADASIL whit respect to the other vascular dementias

En el mundo hay unos 47 millones de personas que padecen demencia, y cada año se registran cerca de 10 millones de nuevos casos. La demencia es una de las principales causas de discapacidad y dependencia entre las personas mayores de 65 años. La demencia vascular constituye la segunda causa de demencia en adultos mayores y en ocasiones su diagnóstico es poco asertivo por la variedad y similitud de síntomas entre las diferentes enfermedades que originan demencia vascular, incluyendo CADASIL (acrónimo inglés de Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy); particularmente el déficit cognitivo es de los síntomas más complejos de diagnóstico, teniendo en cuenta que su manifestación clínica depende de la magnitud y localización de la lesión. La enfermedad de CADASIL, aunque se constituye como una infrecuente causa de demencia vascular de naturaleza hereditaria a nivel mundial, representa una patología de gran importancia en el ámbito nacional, dado que en familias colombianas se ha reportado mutaciones que conllevan a dicha patología. Por lo tanto, su diagnóstico y tratamiento constituyen un reto para el personal clínico, sabiendo que la identificación temprana y precisa es la mejor estrategia para evitar la progresión precoz de la enfermedad y el mejoramiento de la calidad de vida del paciente. De acuerdo con lo anterior, se realizó una revisión de la diferenciación clínica del déficit cognitivo del CADASIL con respecto a las demás demencias vasculares, con el fin de generar una herramienta que apoye la diferenciación clínica de dicha patología.

In the world, there are approximately 47 million people who have dementia, and every year they register near 10 million new cases. The dementia is one of the principal reasons for disability and dependence between people older than 65 years old. Vascular dementia constitutes the second reason of dementia in the elders, and sometimes the diagnosis is slightly assertive because of the variety and similarity of symptoms between the different diseases that originate vascular dementia, including CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy). Particularly, the cognitive deficit is one of the most complex symptoms of diagnosis, bearing in mind that its clinical manifestation depends on the magnitude and location of the injury. CADASIL disease, though it constituted as an infrequent reason of vascular dementia of hereditary nature worldwide, represents a pathology of great importance in the national area, because, in Colombian families, there have been reported mutations that carry to the above-mentioned pathology. Therefore, its diagnosis and treatment constitute a challenge for the clinical personnel, knowing that the early and precise identification is the best strategy to avoid the rapid progression of the disease and the improvement of the quality of life of the patient. In agreement with the previous information, there was made a review of the clinical differentiation of the cognitive deficit of CADASIL regarding other vascular dementias, to generate a tool that supports the clinical differentiation of the pathology mentioned above.

Perfil neuropsicológico y efectos de la rehabilitación cognitiva en la leucemia linfoblástica aguda: a propósito de un caso / Neuropsychological profile and cognitive rehabilitation training effects on acute lymphoblastic leukaemia: a case study

La Leucemia Linfoblástica Aguda (LLA) infantil es el cáncer pediátrico más frecuente. Actualmente cuenta con un alto porcentaje de supervivencia, pero dichos pacientes presentan secuelas cognitivas secundarias a la enfermedad debidas, principalmente, al tratamiento médico recibido para evitar la recidiva del cáncer. Por lo tanto, resulta necesaria la implementación de programas de rehabilitación cognitiva específicos para este tipo de población. Es por ello que el objetivo del presente estudio fue describir los déficits cognitivos en un varón de 17 años que fue diagnosticado con LLA a los 9 años. Tras la valoración neuropsicológica inicial se desarrolló un programa de rehabilitación cognitiva intensivo durante dos años consecutivos. Realizamos un estudio pre-post en el que administramos el Conners Continuous Performance Test (CPT-II) y la Escala de Inteligencia de Wechsler para niños (WISC-IV). Los resultados, antes de la intervención, mostraron que el paciente manifestaba una menor velocidad de procesamiento y dificultades de atención sostenida y alternante, comprensión verbal y razonamiento perceptivo. Además, también presentó un número considerable de errores perseverativos, signo de dificultades de flexibilidad cognitiva y control inhibitorio. Dichos déficits mejoraron notablemente tras el programa de rehabilitación cognitiva. En conclusión, nuestro estudio pone de manifiesto la necesidad de aplicar programas de rehabilitación cognitiva tempranos para paliar las secuelas cognitivas derivadas de la LLA y de su tratamiento médico, así como mejorar la calidad de vida del paciente, ya que las mejoras cognitivas redundarán en su rendimiento académico y en su funcionamiento cotidiano.

Childhood Acute Lymphoblastic Leukemia (ALL) is the most common pediatric cancer. It currently has a high survival rate, but these patients have cognitive sequelae secondary to the disease, mainly due to the medical treatment received to prevent cancer recurrence. Therefore, it is necessary to implement specific cognitive rehabilitation programs for this type of population. Hence, the main objective of this study was to describe cognitive deficits in a 17-year-old male who was diagnosed with ALL when he was 9 years old. After the initial neuropsychological evaluation, an intensive cognitive rehabilitation program was developed during two consecutive years. We conducted a pre-post study in which we administered the Conners Continuous Performance Test (CPT-II) and the Wechsler Intelligence Scale for Children (WISC-IV). Results, before the intervention, showed that the patient presented a lower processing speed and difficulties of sustained and alternating attention, verbal comprehension and perceptive reasoning; in addition to a large number of perseverative errors, sign of self-monitoring difficulties and inhibitory control. These deficits improved markedly after a program of cognitive rehabilitation. In conclusion, our study highlights the need to apply early cognitive rehabilitation programs to alleviate the cognitive sequelae derived from ALL and its medical treatment. In addition, any improvement in their cognitive capabilities will have a positive impact in their academic performance and quality of life.

Alteraciones del neurodesarrollo en pacientes con hipotiroidismo congénito: Recomendaciones para el seguimiento / Neurodevelopmental assessment of patients with congenital hypothyroidism

Congenital hypothyroidism (CH) is the most common cause of preventable cognitive disability worldwide. Generally, it is produced by an alteration in the embryogenesis of the thyroid gland or by an alteration in the synthesis of thyroid hormones, which determine that affected patients have low or absent thyroid hormone concentrations. The importance of this fact is that brain development during the first three years of life is highly dependent on thyroid hormones. Prior to the implementation of national neonatal screening programs around the world, 8 to 27% of children with CH had an IQ lower than 70. Nowadays, this percentage is close to 0 in countries that have implemented the program. In Chile, CH neonatal screening program achieved national coverage in 1996. Currently, the incidence of the disease in our country is 1: 3163. The degree of disability produced by CH not only depends on the time of detection of the disease and the prompt start of therapy, but also on an adequate monitoring. Despite screening programs, neurocognitive impairment in schoolchildren and teenagers with CH is still observed, reflected in lower scores in cognitive, language and gross motor assessments, receptive communication, expressive communication, fine motor and gross motor skills compared to healthy children. Also, lesser achievements in learning and language disorders are observed. The objective of this review is to update the information available on neurodevelopment of patients with CH.

Cognitive performance of premature infants: association between bronchopulmonary dysplasia and cognitive skills. Cross-sectional study / Desempenho cognitivo de prematuros: associação da displasia broncopulmonar com as habilidades cognitivas. Estudo transversal

ABSTRACT CONTEXT AND OBJECTIVE: Children born prematurely often have worse cognitive performance than those born at term regarding skills such as memory, attention and processing speed. Bronchopulmonary dysplasia may compromise cognitive development. The aims here were: a) To describe the cognitive performance of preterm infants with very low birth weight; b) To investigate its association with bronchopul-monary dysplasia adjusted for sociodemographic, neonatal and post-neonatal factors. DESIGN AND SETTING: Cross-sectional study developed in a public tertiary-care hospital. METHODS: To evaluate cognition among 112 children, we applied an intelligence scale (Wechsler scale). The average scores for children with and without bronchopulmonary dysplasia were compared across the fve domains of the scale. Associations with bronchopulmonary dysplasia were investigated for domains that showed signifcant diferences between the two groups. Associations between exposure and outcome were estimated via multivariate logistic regression. RESULTS: There were no diferences in averages for the full-scale intelligence quotient, verbal intelligence quotient, performance intelligence quotient and general language composite domains. The processing speed quotient was the only domain that presented a signifcant diference between the two groups (P = 0.02). Among the children with bronchopulmonary dysplasia, low full-scale intelligence quotient was observed in 28.1%. In the multivariate analysis, bronchopulmonary dysplasia (odds ratio: 3.1; 95conf-dence interval: 1.1-8.7) remained associated with the outcome of processing speed quotient. CONCLUSION: Bronchopulmonary dysplasia was an independent risk factor for alteration of the processing speed quotient.

RESUMO CONTEXTO E OBJETIVO: Crianças nascidas prematuras com frequência apresentam pior desempenho cognitivoque as nascidas a termo em habilidades como memória, atenção, velocidade de processamento. A displasia broncopulmonar pode comprometer o desenvolvimento cognitivo. Os objetivos aqui foram: a) Descrever o desempenho cognitivo de crianças nascidas prematuras com muito baixo peso; b) Investigar sua associação com a displasia broncopulmonar ajustada para fatores sócio-demográfcos, neonatais e pós-neonatais. TIPO DE ESTUDO E LOCAL: Estudo transversal desenvolvido em hospital público de cuidados terciários. MÉTODOS: Para a avaliação cognitiva de 112 crianças, aplicamos a escala de inteligência (Wechsler scale). Foram comparadas as médias dos escores das crianças com e sem displasia broncopulmonar nos cinco domínios da escala. A associação com a displasia broncopulmonar foi investigada para os domínios que apresentaram diferença signifcativa entre os dois grupos. A associação entre a exposição e o desfecho foi estimada por regressão logística multivariada. RESULTADOS: Não houve diferença entre as médias dos domínios do quociente de inteligência total, quociente de inteligência verbal, quociente de inteligência de execução e composto de linguagem geral. O quociente de velocidade de processamento foi o único domínio que apresentou diferença signifcativa entre os dois grupos (P = 0,02). Entre as crianças com displasia broncopulmonar, quociente de inteligência total baixo ocorreu em 28,1%. Na análise multivariada, a displasia broncopulmonar (odds ratio: 3,1; intervalo de confança: 1,1-8,7) permaneceu associada ao desfecho quociente de velocidade de processamento. CONCLUSÃO: A displasia broncopulmonar foi um fator de risco independente para alteração no quociente de velocidade de processamento.

Functional decline in the elderly with MCI: Cultural adaptation of the ADCS-ADL scale / Declínio funcional em idosos com comprometimento cognitivo leve: adaptação cultural da escala ADCS-ADL

Summary Objective: Translate, transcultural adaptation and application to Brazilian Portuguese of the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) scale as a cognitive screening instrument. Method: We applied the back translation added with pretest and bilingual methods. The sample was composed by 95 elderly individuals and their caregivers. Thirty-two (32) participants were diagnosed as mild cognitive impairment (MCI) patients, 33 as Alzheimer's disease (AD) patients and 30 were considered as cognitively normal individuals. Results: There were only little changes on the scale. The Cronbach alpha coefficient was 0.89. The scores were 72.9 for control group, followed by MCI (65.1) and by AD (55.9), with a p-value < 0.001. The ROC curve value was 0.89. We considered a cut point of 72 and we observed a sensibility of 86.2%, specificity of 70%, positive predictive value of 86.2%, negative predictive value of 70%, positive likelihood ratio of 2.9 and negative likelihood ratio of 0.2. Conclusion: ADCS-ADL scale presents satisfactory psychometric properties to discriminate between MCI, AD and normal cognition.

Resumo Objetivo: Tradução, adaptação transcultural para o português brasileiro e aplicação da escala Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) como instrumento de triagem cognitiva. Método: Retrotradução associada ao método bilíngue e de pré-teste. A amostra foi constituída por 95 idosos e seus respectivos acompanhantes, sendo 30 controles, 32 portadores de comprometimento cognitivo leve (CCL) e 33 portadores de demência de Alzheimer (DA) em fase inicial. Resultados: Um pequeno número de modificações ocorreu na escala. O coeficiente alpha de Cronbach foi 0,89. O grupo controle pontuou 72,9, seguido pelo CCL (65,1) e pelo DA (55,9), valor p<0,001. A curva ROC demonstrou valor de 0,89. Com o ponto de corte de 72, observamos sensibilidade de 86,2%, especificidade de 70%, valor preditivo positivo de 86,2%, valor preditivo negativo de 70%, razão de verossimilhança positiva de 2,9 e razão de verossimilhança negativa de 0,2. Conclusão: A escala ADCS-ADL apresenta propriedades psicométricas satisfatórias para discriminar entre DA, CCL e cognição normal.

Sex-specific cognitive abnormalities in early-onset psychosis

Objectives: Brain maturation differs depending on the area of the brain and sex. Girls show an earlier peak in maturation of the prefrontal cortex. Although differences between adult females and males with schizophrenia have been widely studied, there has been less research in girls and boys with psychosis. The purpose of this study was to examine differences in verbal and visual memory, verbal working memory, auditory attention, processing speed, and cognitive flexibility between boys and girls. Methods: We compared a group of 80 boys and girls with first-episode psychosis to a group of controls. Results: We found interactions between group and sex in verbal working memory (p = 0.04) and auditory attention (p = 0.01). The female controls showed better working memory (p = 0.01) and auditory attention (p = 0.001) than males. However, we did not find any sex differences in working memory (p = 0.91) or auditory attention (p = 0.93) in the psychosis group. Conclusions: These results are consistent with the presence of sex-modulated cognitive profiles at first presentation of early-onset psychosis.

Estratégias metacognitivas de leitura de crianças com distúrbio de aprendizagem / Metacognitive reading strategies of children with learning disabilities

RESUMO Objetivo verificar o uso de estratégias metacognitivas de leitura de crianças com Distúrbio de Aprendizagem e averiguar se há relação entre este uso e a compreensão de textos. Método participaram 30 crianças, de 8 a 12 anos, de ambos os gêneros, divididas em grupo experimental (GE) - 15 crianças com Distúrbio de Aprendizagem; e grupo controle (GC) - 15 crianças sem dificuldades. Todas foram submetidas à Escala de Estratégias de Leitura e o subteste compreensão de textos do Prolec. A descrição da amostra foi feita em valores de média, mediana, mínimo e máximo. Para análise comparativa entre os grupos, foi utilizado o Teste de Mann-Whitney. O grau de correlação entre as variáveis foi verificado pela Análise de Correlação de Spearman. Foi adotado o nível de significância de 5%. Resultados na pontuação total da escala, o desempenho do GE foi inferior em todas as medidas descritivas com diferença significante em relação ao GC. O GE apresentou desempenho próximo ao das crianças sem dificuldade somente nas estratégias globais. A correlação entre o uso de estratégias metacognitivas e a compreensão de textos foi positiva. Conclusão as crianças com Distúrbio de Aprendizagem evidenciaram déficits na utilização de estratégias metacognitivas de leitura quando comparadas às crianças sem dificuldade de aprendizagem. Quanto melhor o desempenho na escala de estratégias de leitura, melhor foi o desempenho na compreensão dos textos e vice-versa, sugerindo que habilidades metacognitivas para leitura contribuem para a compreensão leitora.

ABSTRACT Purpose to check the use of metacognitive reading strategies in children with learning disabilities and determine whether there is a relationship between their use and text comprehension. Methods the study was conducted on 30 children, aged 8 to 12 years, of both genders, divided into experimental group (EG) - 15 children with learning disabilities; and control group (CG) - 15 children without disability. All children were submitted to the Reading Strategies Scale and Prolec text comprehension subtest. The sample was described in mean, median, minimum and maximum values. Comparative analysis was performed between the groups using the Mann-Whitney test. The degree of correlation between variables was verified by Spearman Correlation Analysis. The significance level was set at 5%. Results across the total scores of the scale, EG performance was lower in all descriptive measures, with a significant difference compared to CG. The EG achieved a performance close to children without difficulties only in global strategies. The correlation between the use of metacognitive strategies and reading comprehension was positive. Conclusion children with learning disabilities showed deficits in the use of metacognitive reading strategies when compared to children without learning disabilities. The better the performance in reading strategies, the better textual comprehension was and vice versa, suggesting that metacognitive reading skills contribute to reading comprehension.

Cognitive performance and psychosocial functioning in patients with bipolar disorder, unaffected siblings, and healthy controls

Objective: To assess cognitive performance and psychosocial functioning in patients with bipolar disorder (BD), in unaffected siblings, and in healthy controls. Methods: Subjects were patients with BD (n=36), unaffected siblings (n=35), and healthy controls (n=44). Psychosocial functioning was accessed using the Functioning Assessment Short Test (FAST). A sub-group of patients with BD (n=21), unaffected siblings (n=14), and healthy controls (n=22) also underwent a battery of neuropsychological tests: California Verbal Learning Test (CVLT), Stroop Color and Word Test, and Wisconsin Card Sorting Test (WCST). Clinical and sociodemographic characteristics were analyzed using one-way analysis of variance or the chi-square test; multivariate analysis of covariance was used to examine differences in neuropsychological variables. Results: Patients with BD showed higher FAST total scores (23.90±11.35) than healthy controls (5.86±5.47; p < 0.001) and siblings (12.60±11.83; p 0.001). Siblings and healthy controls also showed statistically significant differences in FAST total scores (p = 0.008). Patients performed worse than healthy controls on all CVLT sub-tests (p < 0.030) and in the number of correctly completed categories on WCST (p = 0.030). Siblings did not differ from healthy controls in cognitive tests. Conclusion: Unaffected siblings of patients with BD may show poorer functional performance compared to healthy controls. FAST scores may contribute to the development of markers of vulnerability and endophenotypic traits in at-risk populations.

Components of the metabolic syndrome and depressive symptoms in community-dwelling older people: the Bambuí Cohort Aging Study

Objective: To investigate the moderating effect of an increasing number of clustered metabolic syndrome (MetS) components on the association between MetS and depressive symptoms in a population-based cohort of older adults in Brazil. Methods: This analysis used data from the Bambuí Cohort Aging Study. Participants in this cross-sectional study comprised 1,469 community-dwelling older people aged ≥ 60 years. Analyses were performed to assess both the association between depressive symptoms and each individual MetS component and the association between depressive symptoms and clustering of an increasing number of MetS components. Results: High triglyceride level was the individual component that showed the strongest association with depressive symptoms (odds ratio [OR]: 1.47; 95% confidence intervals [95%CI] 1.19-1.81; p < 0.0001). Only the presence of three MetS components was associated with depressive symptoms (OR = 1.53; 95%CI 1.05-2.23; p = 0.025). No graded association was detected between increasing number of clustered MetS components and depressive symptoms. Conclusions: Increasing the number of MetS components did not impact the association with depressive symptoms. The association between high triglyceride level and depressive symptoms highlights the relevance of lipid metabolism abnormalities for the emergence of depressive symptoms in older adults.

Schizophrenia and reelin: a model based on prenatal stress to study epigenetics, brain development and behavior

Schizophrenia is a severe psychiatric disorder that results in a significant disability for the patient. The disorder is characterized by impairment of the adaptive orchestration of actions, a cognitive function that is mainly dependent on the prefrontal cortex. This behavioral deficit, together with cellular and neurophysiological alterations in the prefrontal cortex, as well as reduced density of GABAergic cells and aberrant oscillatory activity, all indicate structural and functional deficits of the prefrontal cortex in schizophrenia. Among the several risk factors for the development of schizophrenia, stress during the prenatal period has been identified as crucial. Thus, it is proposed that prenatal stress induces neurodevelopmental alterations in the prefrontal cortex that are expressed as cognitive impairment observed in schizophrenia. However, the precise mechanisms that link prenatal stress with the impairment of prefrontal cortex function is largely unknown. Reelin is an extracellular matrix protein involved in the development of cortical neural connectivity at embryonic stages, and in synaptic plasticity at postnatal stages. Interestingly, down-regulation of reelin expression has been associated with epigenetic changes in the reelin gene of the prefrontal cortex of schizophrenic patients. We recently showed that, similar to schizophrenic patients, prenatal stress induces down-expression of reelin associated with the methylation of its promoter in the rodent prefrontal cortex. These alterations were paralleled with altered prefrontal cortex functional connectivity and impairment in prefrontal cortex-dependent behavioral tasks. Therefore, considering molecular, cellular, physiological and behavioral evidence, we propose a unifying framework that links prenatal stress and prefrontal malfunction through epigenetic alterations of the reelin gene.

Depressive signs and cognitive performance in patients with a right hemisphere stroke / Sinais depressivos e desempenho cognitivo em pacientes com lesão de hemisfério direito

ABSTRACT Purpose: This study investigated the influence of suggestive signs of depression (SSD) in right-hemisphere brain-damaged (RHD) patients following a stroke on their cognitive performance measured by a brief neuropsychological assessment battery. Methods: Forty-two adults with RHD after a single episode of stroke and 84 matched controls participated in this study. They were assessed by means of the Geriatric Depression Scale and by Brief Neuropsychological Assessment Battery NEUPSILIN. Results: Almost half of the patients showed SSD. The RHD group with SSD (RHD+) showed poorer performance in at least one task among all evaluated cognitive domains (concentrated attention, visual perception, working memory, episodic verbal memory and semantic memory, auditory and written language, constructional praxia and verbal fluency). Conclusion: The association of depression and RHD seems to enhance the occurrence and the severity of cognitive déficits. A brief neuropsychological assessment can be useful to identify cognitive impairment caused by this neuropsychiatric disorder.

RESUMO Objetivo: Investigar a influência de sinais sugestivos de depressão (SSD) em pacientes com acidente vascular cerebral (AVC) de hemisfério direito (HD) no desempenho em um instrumento de avaliação neuropsicológica breve. Métodos: Participaram 42 adultos pós-episódio único de lesão cerebrovascular de HD (LHD) e 84 controles emparelhados. Administraram-se a Escala de Depressão Geriátrica GDS-15 e o Instrumento de Avaliação Neuropsicológica Breve NEUPSILIN. Resultados: Aproximadamente metade da amostra de pacientes apresentou SSD. O grupo com LHD com SSD (LHD+) obteve desempenho inferior em no mínimo uma tarefa dos domínios cognitivos avaliados (atenção concentrada, percepção visual, memória de trabalho, memória verbal episódica e memória semântica; linguagem oral e escrita; praxia construtiva e fluência verbal). Conclusão: A associação de depressão e LHD parece aumentar a extensão dos déficits cognitivos, sendo que uma avaliação neuropsicológica breve pode ser útil na identificação de alterações cognitivas neste quadro neuropsiquiátrico.

Cognitive deficits in post-stroke aphasia / Déficits cognitivos na afasia pós-AVE

The assessment of aphasics’ cognitive performance is challenging and such patients are generally excluded from studies that describe cognitive deficits after stroke. We evaluated aphasics’ performance in cognitive tasks compared to non-aphasic subjects. A sample of 47 patients (21 aphasics, 17 non-aphasics with left hemisphere lesions and 9 non-aphasics with right hemisphere lesions) performed cognitive tasks (attention, verbal and visual memory, executive functions, visuospatial skills and praxis). Aphasic patients performed poorer than all non-aphasics in Digit Span (p < 0.001), Clock-Drawing Test (p = 0.006), Verbal memory (p = 0.002), Visual Memory (p < 0.01), Verbal Fluency (p < 0.001), and Gesture Praxis (p < 0.001). Aphasia severity correlated with performance in Trail Making test part B (p = 0.004), Digit Span forward (p < 0.001) and backwards (p = 0.011), and Gesture Praxis (p = 0.002). Aphasia is accompanied by deficits not always easy to be evaluated by cognitive tests due to speech production and motor impairments. Assessment of cognitive functions in aphasics might contribute to optimize therapeutic intervention.

A avaliação cognitiva de afásicos é difícil e tais pacientes são frequentemente excluídos dos estudos que descrevem déficits cognitivos pós-AVC. Avaliamos o desempenho de afásicos em tarefas cognitivas comparados a não-afásicos. Um grupo de 47 indivíduos (21 afásicos, 17 não-afásicos com lesão à E e 9 não-afásicos com lesão à D) realizou testes cognitivos (atenção, memória verbal e visual, funções executivas, habilidades visoespaciais e praxias). Afásicos apresentaram pior desempenho do que não-afásicos em Extensão de Dígitos (p < 0,001), Desenho do Relógio (p = 0,006), Memória Verbal (p = 0,002), Memória Visual (p < 0,01), Fluência Verbal (p < 0,001) e Praxias Gestuais (p < 0,001). A gravidade da afasia correlacionou-se com o desempenho no Teste de Trilhas parte B (p = 0,004), Extensão de Dígitos direta (p < 0,001) e inversa (p = 0,01), e Praxias Gestuais (p = 0,002). Afasia é acompanhada por déficits difíceis de ser avaliados devido às deficiências de expressão e motoras. A avaliação das funções cognitivas em afásicos pode otimizar a intervenção terapêutica.

Memory deficit associated with increased brain proinflammatory cytokine levels and neurodegeneration in acute ischemic stroke / Déficit de memória associado ao aumento dos níveis cerebrais de citocinas pró-inflamatórias e neurodegeneração na isquemia cerebral aguda

The present study aimed to investigate behavioral changes and neuroinflammatory process following left unilateral common carotid artery occlusion (UCCAO), a model of cerebral ischemia. Post-ischemic behavioral changes following 15 min UCCAO were recorded 24 hours after reperfusion. The novel object recognition task was used to assess learning and memory. After behavioral test, brains from sham and ischemic mice were removed and processed to evaluate central nervous system pathology by TTC and H&E techniques as well as inflammatory mediators by ELISA. UCCAO promoted long-term memory impairment after reperfusion. Infarct areas were observed in the cerebrum by TTC stain. Moreover, the histopathological analysis revealed cerebral necrotic cavities surrounded by ischemic neurons and hippocampal neurodegeneration. In parallel with memory dysfunction, brain levels of TNF-a, IL-1b and CXCL1 were increased post ischemia compared with sham-operated group. These findings suggest an involvement of central nervous system inflammatory mediators and brain damage in cognitive impairment following unilateral acute ischemia.

O presente estudo teve como objetivo investigar alterações comportamentais e processos inflamatórios na isquemia cerebral induzida pela oclusão unilateral da carótida comum esquerda (UCCAO) em camundongos. As alterações comportamentais foram avaliadas após 15 minutos de isquemia e 24 horas de reperfusão. O teste de reconhecimento de objetos foi utilizado para avaliação da memória e do aprendizado. Em seguida, os animais foram mortos e os encéfalos foram coletados e processados para avaliação das alterações patológicas pelas técnicas de TTC e H&E, assim como da dosagem de mediadores inflamatórios por ELISA. A UCCAO promoveu alterações de memória após a reperfusão. Foram visualizadas áreas de infarto cerebral pela coloração de TTC e cavidades necróticas circundadas por neurônios isquêmicos no cérebro e neurodegeneração hipocampal. A UCCAO causou aumento dos níveis encefálicos de TNF-a, IL-1b e CXCL1. Estes achados demonstraram o envolvimento dos mediadores inflamatórios no sistema nervoso central e da neurodegeneração no déficit cognitivo após isquemia cerebral aguda.

Motor, linguistic, personal and social aspects of children with Down syndrome

AbstractA global developmental delay is expected from Down syndrome, affecting motor, cognitive, linguistic and personal-social skills. However, not always these delays are proportional; different conditions occur due to several intrinsic and extrinsic variables that must be controlled to form groups of greater homogeneity.Objective To enhance personal-social, fine motor-adaptive, gross motor and linguistic skills among children with Down syndrome and compare them with typically developing children, matched for gender, socioeconomic status and mental age, while controlling some variables that interfere with the global development.Methods The ethical aspects were fulfilled (Case No. 040/2009). The following inclusion criteria were considered: participants without a history of prematurity, very low birth weight, congenital hypothyroidism, significant hearing and vision problems, and signs of Autism Spectrum Disorder. After the inclusion criteria were considered, 40 children participated in the study, of which 20 had Down syndrome (experimental group - EG), these being of both genders and with chronological ages ranging from 38 to 63 months, and the other 20 being typically developing children (control group - CG), matching the EG in terms of gender, socioeconomic status and mental age, with this age ranging from 13 to 50 months. The evaluation consisted in applying the Denver Developmental Screening Test II, a test that assesses areas such as personal-social, fine motor-adaptive, linguistic and gross motor development. The results were subjected to statistical analysis using Student’s t-test.Results A statistically significant difference was verified between the groups for the language and fine motor-adaptive areas.Conclusion Children with Down syndrome showed lower performance in language and fine motor skills when compared with typically developing children. There was no statistically significant difference in gross motor and personal-social areas. It is worth mentioning the importance of controlling the variables to deal with more homogeneous groups.

Enfermedad de Lyme en pediatría: distintas caras, una misma enfermedad. Serie de casos / Lyme disease in Pediatrics: different faces, the same disease. Cases series

La enfermedad de Lyme es producida por la espiroqueta Borrelia burgdorferi, que se transmite mediante la picadura de las garrapatas del género Ixodes ricinus. Se caracteriza por la aparición de un eritema migratorio en la zona de la picadura en las fases iniciales. Su diagnóstico se retrasa en gran parte de los casos y se presenta con formas diseminadas o tardías. El diagnóstico es fundamentalmente clínico; la serología suele ser negativa en las fases precoces, pero sirve de apoyo en el caso de las formas más avanzadas. El tratamiento se realiza con antibiótico oral durante 14-28 días, salvo en formas recurrentes o con afectación del sistema nervioso central. Presentamos cuatro casos de borreliosis de Lyme en niños con el fin de dar a conocer distintas formas de presentación de esta entidad y su manejo en la población pediátrica.

Lyme disease is caused by Borrelia burgdorferi infection which is transmittedby Ixodes ricinus. Erythema migrans, a rash spreading from the site of a tick bite, is the earliest and most common manifestation of the disease. If untreated, late manifestations of disseminated disease, mainly neurological and musculoskeletal, may occur. Serologic studies are usually negative in early stages and are not necessary to confirm the diagnosis in cases of erythema migrans. Laboratory confirmation is needed for disseminated disease. Most presentations, including facial nerve palsy, can be treated with oral antibiotics. Ceftriaxone is recommended in other cases of neuroborreliosis. Four cases of Lyme disease in children are reported to illustrate the different presentations of this disease and its management in children.

An unexpected cause of severe and refractory PTH-independent hypercalcemia: case report and literature review

Hypercalcemia is a common condition in the internal medicine practice. Sometimes its cause is not readily apparent, so extensive investigation is appropriate. Here we report an unexpected cause for hypercalcemia in an elderly woman. The case of an 82-years old woman with PTH-independent hypercalcemia, lymphocytosis, normal serum 1,25 (OH)vitamin D levels, and low serum PTHrp levels, is described. Medical history and complementary investigation were unremarkable, except for increased metabolic activity in the glutei regions, as measured by whole body 18F-FDG PET-CT. Reviewing her medical history, her sister recalled that she had been submitted to intramuscular methylmethacrylate injections, for cosmetic purposes, five years before presentation, which was confirmed by muscle biopsy. Low calcium intake, parenteral bisphosphonates, calcitonin, and glucocorticoids were used to control serum calcium levels. Methylmethacrylate injections, used cosmetically, are a new cause for hypercalcemia, even after many years. Hypercalcemia was probably due to calcitriol overproduction in foreign body granulomas. Persistent reactive lymphocytosis could be a clue for this inflammatory cause of hypercalcemia. Arch Endocrinol Metab. 2015;59(3):277-80.

Non-motor signs in Parkinson’s disease: a review / Sinais não motores na doença de Parkinson: uma revisão

During the past decade the view of Parkinson’s disease (PD) as a motor disorder has changed significantly and currently it is recognized as a multisystem process with diverse non-motor signs (NMS). In addition to been extremely common, these NMS play a major role in undermining functionality and quality of life. On the other hand, NMS are under recognized by physicians and neglected by patients. Here, we review the most common NMS in PD, including cognitive, psychiatric, sleep, metabolic, and sensory disturbances, discuss the current knowledge from biological, epidemiological, clinical, and prognostic standpoints, highlighting the need for early recognition and management.

No decorrer da última década, a visão da doença de Parkinson (DP) como um distúrbio de movimento puro mudou significativamente, sendo atualmente reconhecida como um processo multisistêmico com diversos sinais não motores (SNM). Além de serem extremamente comuns, estes SNM têm um impacto muito significativo na limitacão funcional e da qualidade de vida na DP. Por outro lado, os SNM são mal reconhecidos pelos clínicos e negligenciados pelos pacientes. Nessa revisão os SNM mais comuns na DP foram detalhados, incluindo distúrbios cognitivos, psiquiátricos, do sono, metabólicos, e sensitivos; e discutindo o conhecimento atual sob o ponto de vista biológico, epidemiólogico, clínico e prognóstico, destacando a necessidade de reconhecimento e abordagem terapêutica precoces.