Validade e utilidade diagnóstica de escalas de avaliação de depressão e testes neuropsicológicos nos principais transtornos psiquiátricos após traumatismo cranioencefálico grave

Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências Biológicas, Programa de Pós-Graduação em Neurociências, Florianópolis, 2014.Introdução: o traumatismo cranioencefálico (TCE) grave é uma importante causa de morbidade e mortalidade. Transtornos cognitivos e psiquiátricos são frequentes em sobreviventes de TCE grave, principalmente depressão e alteração de personalidade. Poucos estudos investigaram o valor de testes psicométricos para o rastreamento e o auxílio diagnóstico desses transtornos. Objetivos: definir o valor de testes psicométricos no rastreamento e no auxílio diagnóstico da depressão e alteração de personalidade após TCE grave. Metodologia: 46 pacientes consecutivamente hospitalizados por TCE grave realizaram avaliação psiquiátrica e neuropsicológica na fase crônica do trauma. O diagnóstico de depressão foi definido pela Entrevista Clínica Estruturada para os Transtornos do Eixo I do DSM-IV (SCID-I) e o diagnóstico de alteração de personalidade foi feito de acordo com a 4ª edição revisada do Manual Diagnóstico e Estatístico de Transtornos Mentais (DSM-IV-TR). Os seguintes instrumentos foram aplicados: Escala de Depressão de Hamilton (HAM-D); Inventário de Depressão de Beck (BDI); Escala Hospitalar de Ansiedade e Depressão (HADS); teste de fluência verbal; testes de Vocabulário, Semelhanças, Dígitos e Cubos da 3ª edição da Escala de Inteligência de Wechsler para Adultos (WAIS-III); testes de memória lógica e reprodução visual da 3ª edição da Escala de Memória de Wechsler (WMS-III); e Teste de Aprendizagem Auditivo-verbal de Rey (RAVLT). Foi feita uma análise de característica de operação do receptor (ROC) utilizando os testes psicométricos como variáveis preditoras e os diagnósticos psiquiátricos como variáveis de desfecho. Resultados: todas as escalas de avaliação de depressão demonstraram capacidade discriminativa para depressão, mas não para alteração de personalidade, enquanto que vários testes neuropsicológicos tiveram capacidade discriminativa para alteração de personalidade. Para a HAM-D, com o desfecho depressão, a área sob a curva (AUC) foi 0,89 com sensibilidade de 92,9% e especificidade 78,1% no ponto de corte ótimo; para a BDI a AUC foi 0,946 com sensibilidade 92,3% e especificidade 96,7%; e para a HADS a AUC foi 0,947 com sensibilidade 100% e especificidade 80,7%. Os seguintes testes tiveram boa validade global (AUC maior que 0,8) com o desfecho alteração de personalidade: RAVLT evocação imediata (sensibilidade 84,6%, especificidade 73,3% no ponto de corte ótimo), evocação tardia (sensibilidade 76,9%, especificidade 76,7%) e reconhecimento (sensibilidade 91,7%, especificidade 70,8%); Reprodução visual da WMS-III evocação imediata (sensibilidade 92,3%, especificidade 68,9%); e fluência verbal fonêmica (sensibilidade 84,6%, especificidade 72,4%). Conclusões: as escalas de avaliação de depressão podem ser úteis para rastreamento e auxílio diagnóstico da depressão em sobreviventes de TCE grave, e vários testes neuropsicológicos podem ter a mesma utilidade para alteração de personalidade.Abstract : Introduction: severe traumatic brain injury (TBI) is a major cause of mortality and morbidity. Cognitive deficits and psychiatric disorders are frequent in severe TBI survivors, especially depression and personality change. Few studies have assessed the value of psychometric tests in the screening and as auxiliary diagnostic tools for these disorders. Objectives: to define the value of psychometric tests in the screening and as auxiliary diagnostic tools for depression and personality change following TBI. Methodology: 46 patients consecutively hospitalized due to severe TBI were subjected to psychiatric and neuropsychological evaluation in the chronic phase of trauma. The diagnosis of depression was defined by the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) and the diagnosis of personality change due to TBI was made according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR). The following psychometric tools were applied: Hamilton Depression Rating Scale (HAM-D); Beck Depression Inventory (BDI); Hospital Anxiety and Depression Scale (HADS); verbal fluency test; Wechsler Adult Intelligence Scale 3th edition (WAIS-III) Vocabulary, Similarities, Digit Span and Block Design tests; Wechsler Memory Scale 3th edition (WMS-III) Logical Memory and Visual Reproduction tests; and the Rey Auditory Verbal Learning Test (RAVLT). ROC analysis was performed using psychometric tests as predictors and psychiatric diagnosis as outcome. Results: all depression rating scales showed discriminatory ability for depression, but not for personality changes, whereas several neuropsychological tests demonstrated the opposite pattern. For the HAM-D with depression as outcome the area under the curve (AUC) was 0.89 with a sensitivity of 92.9% and a specificity of 78.1% at the optimal cut-off point; for the BDI the AUC was 0.946 with a sensitivity of 92.3% and a specificity of 96.7%; and for the HADS the AUC was 0.947 with a sensitivity of 100% and a specificity of 80.7%. The following neuropsychological tests showed a good overall validity (AUC higher than 0.8) with personality change as outcome: RAVLT immediate recall (sensitivity 84.6%, specificity 73.3% at the optimal cut-off point), delayed recall (sensitivity 76.9%, specificity 76.7%) and recognition (sensitivity 91.7%, specificity 70.8%); WMS-III Visual Reproduction immediate recall (sensitivity 92.3%, specificity 68.9%); and phonemic verbal fluency (sensitivity 84.6%, specificity 72.4%). Conclusions: depression rating scales may be useful in the screening and as auxiliary diagnostic tools for depression in severe TBI survivors, and several neuropsychological tests may have the same utility for personality change

Emocionalidade, cognição e estresse oxidativo em um modelo de traumatismo crânio-encefálico em camundomgos

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências Biológicas, Programa de Pós-Graduação em Neurociências, Florianópolis, 2010o traumatismo crânio-encefálico (TCE) é caracterizado por elevadas taxas de incidência, mortalidade e morbidade. Prejuízos cognitivos e síndromes psiquiátricas se destacam entre as seqüelas do TCE. Evidencias indicam que os danos secundários têm um importante papel na evolução do TCE e na gênese das seqüelas. Objetivos: padronizar um modelo de TCE em camundongos e investigar seus efeitos na emocionalidade, cognição, histologia e estresse oxidativo. Materiais e métodos: um aparato de queda de peso foi desenvolvido para indução de TCE em camundongos utilizando projéteis de massa 10 g, 12,5 g e 15 g. Após avaliação neurológica em fase aguda, os animais se recuperaram por 10 dias e foram submetidos a uma bateria de testes comportamentais relacionados à emocionalidade e cognição. Parâmetros de estresse oxidativo foram mensurados em córtex cerebral e hipocampo nos períodos de 2 h, 24 h e 14 dias após o trauma. Uma análise histológica qualitativa também foi realizada. Resultados: projéteis de maior massa induziram maior gravidade de trauma. Os camundongos submetidos ao trauma com o projétil de 10 g apresentaram aumento no comportamento tipo-ansioso e depressivo. Os camundongos dos grupos 12,5 g e 15 g apresentaram prejuízos de memória. Esse último grupo também apresentou aumento na atividade locomotora. Na análise histológica, os camundongos do grupo 10 g não tiveram anormalidades aparentes e os camundongos dos grupos 12.5 g e 15 g mostraram dano tecidual extensivo. Alterações indicativas de estresse oxidativo foram observadas nos animais do grupo 12,5 g nos períodos de 24 h e 14 dias. Conclusões: o modelo foi capaz de gerar em camundongos alterações comportamentais e bioquímicas comparáveis às observadas em pacientes com TCE. O modelo demonstrou potencial para uso em futuros estudos abordando os mecanismos e o tratamento do TCE e suas seqüelas.Traumatic brain injury (TBI) is characterized by high rates of incidence, mortality and morbidity. Cognitive deficits and psychiatric syndromes stand out among TBI sequelae. Evidences indicate that secondary injury plays an important role in the evolution of TBI and in the genesis of its sequelae. Objectives: to standardize a model of TBI in mice and investigate its effects on emotionality, cognition, histology and oxidative stress. Materials and methods: a weight-drop device was developed to induce TBI in mice using projectiles of 10 g, 12.5 g and 15 g. After acute neurological evaluation, mice recovered for 10 days and then were subjected to a behavioral test battery related to emotionality and cognition. Parameters of oxidative stress were measured in the prefrontal cortex and hippocampus at 2 h, 24 h and 14 days after trauma. A histological analysis was also performed. Results: projectiles of greater mass induced greater severity of trauma. Mice subjected to trauma with the 10 g projectile showed increased anxiety- and depression-like behavior. Mice of 12.5 g and 15 g groups showed robust memory deficits. The latter group also presented increased locomotor activity. In the qualitative histological analysis, mice of 10 g group did not show obvious abnormalities and mice of 12.5 g and 15 g groups showed extensive tissue damage. Changes indicating oxidative stress were found in mice of 12.5 g group at 24 h and 14 days after trauma. Conclusions: the model was able to generate in mice behavioral and biochemical changes comparable to those seen patients with TBI. The model demonstrated potential for use in future studies approaching mechanisms and treatment of TBI and its sequelae

Predictors of Hospital Mortality and the Related Burden of Disease in Severe Traumatic Brain Injury: A Prospective Multicentric Study in Brazil

Traumatic brain injury (TBI) is a worldwide social, economic, and health problem related to premature death and long-term disabilities. There were no prospective and multicentric studies analyzing the predictors of TBI related mortality and estimating the burden of TBI in Brazil. To address this gap, we investigated prospectively: (1) the hospital mortality and its determinants in patients admitted with severe TBI we analyzed in three reference centers; (2) the burden of TBI estimated by the years of life lost (YLLs) due to premature death based on the hospital mortality considering the hospital mortality. Between April 2014 and January 2016 (22 months), all the 266 patients admitted with Glasgow coma scale (GCS), ≤ 8 admitted in three TBI reference centers were included in the study. These centers cover a population of 1,527,378 population of the Santa Catarina state, Southern Brazil. Most patients were male (n = 230, 86.5%), with a mean (SD) age of 38 (17) years. Hospital mortality was 31.1% (n = 83) and independently associated with older age, worse cranial CT injury by the Marshall classification, the presence of subarachnoid hemorrhage in the CT, lower GCS scores and abnormal pupils at admission. The final multiple logistic regression model including these variables showed an overall accuracy for hospital mortality of 77.9% (specificity 88.6%, sensitivity 53.8%, PPV 67.7%, and NPV 81.1%). The estimated annual incidence of hospitalizations and mortality due to severe TBI were 9.5 cases and 5.43 per 100,000 inhabitants, respectively. The estimated YLLs in 22 months, in the 2 metropolitan areas were 2,841, corresponding to 1,550 YLLs per year and 101.5 YLLs per 100,000 people every year. The hospital mortality did not change significantly since the end of the 1990s and was similar to other centers in Brazil and Latin America. Significant predictors of hospital mortality were the same as those of studies worldwide, but their strength of association seemed to differ according to countries income. Present study results question the extrapolation of TBI hospital mortality models for high income to lower- and middle-income countries and therefore have implications for TBI multicentric trials including countries with different income levels

Guias sobre crises não epilépticas psicogênicas para pacientes e médicos

As crises não epilépticas psicogênicas (CNEP) são classificadas como um transtorno conversivo e possuem uma etiologia psicogênica. Apesar de haver diferenças semiológicas claras entre as CNEPs e as crises epilépticas, ambas as condições são frequentemente confundidas e, geralmente, são inicialmente tratadas como epilepsia até que o diagnóstico seja corrigido. Ademais, há a possibilidade de um indivíduo apresentar ambas as condições. Desse modo, o diagnóstico errôneo é um fator de deterioro prognóstico dos indivíduos acometidos somente por CNEP em consequência do tratamento inadequado da condição, o que pode perdurar por anos. Assim, deve-se preconizar a difusão do conhecimento e a conscientização sobre o que são CNEPs, sua prevalência e sua importância, a fim de que haja um menor intervalo de tempo entre o início dos sintomas e seu diagnóstico, melhorando, por conseguinte, a qualidade de vida do paciente. Assim, é objetivo deste trabalho a criação de dois infográficos: um destinado à população geral e o outro, aos médicos, com a finalidade de fornecer informações e de conscientizar a população sobre os principais tópicos acerca das CNEPs, visando alcançar os objetivos supracitados

Luteinizing Hormone and Testosterone Levels during Acute Phase of Severe Traumatic Brain Injury: Prognostic Implications for Adult Male Patients

Traumatic brain injury (TBI) is a worldwide core public health problem affecting mostly young male subjects. An alarming increase in incidence has turned TBI into a leading cause of morbidity and mortality in young adults as well as a tremendous resource burden on the health and welfare sector. Hormone dysfunction is highly prevalent during the acute phase of severe TBI. In particular, investigation of the luteinizing hormone (LH) and testosterone levels during the acute phase of severe TBI in male has identified a high incidence of low testosterone levels in male patients (36.5–100%) but the prognostic significance of which remains controversial. Two independent studies showed that normal or elevated levels of LH levels earlier during hospitalization are significantly associated with higher mortality/morbidity. The association between LH levels and prognosis was independent of other predictive variables such as neuroimaging, admission Glasgow coma scale, and pupillary reaction. The possible mechanisms underlying this association and further research directions in this field are discussed. Overall, current data suggest that LH levels during the acute phase of TBI might contribute to accurate prognostication and further prospective multicentric studies are required to develop more sophisticated predictive models incorporating biomarkers such as LH in the quest for accurate outcome prediction following TBI. Moreover, the potential therapeutic benefits of modulating LH during the acute phase of TBI warrant investigation

Decline in word-finding: The objective cognitive finding most relevant to patients after mesial temporal lobe epilepsy surgery

Pauli C, Rodrigues de Oliveira Thais ME, Guarnieri R, et al. Decline in word-finding: The objective cognitive finding most relevant to patients after mesial temporal lobe epilepsy surgery. EPILEPSY & BEHAVIOR. 2017;75:218-224.Purpose: The purpose of this study was to investigate the following: i) the objective impairment in neuropsychological tests that were associated with the subjective perception of cognitive function decline in Brazilian patients who underwent mesial temporal lobe epilepsy (MTLE) surgery and ii) the predictive variables for those impaired objective neuropsychological tests. Methods: Forty-eight adults with MTLE (27 right HS and 23 male) were divided according to their perception of changes (Decline or No-decline) of cognitive function domain of the QOLIE-31 questionnaire applied before and 1 year after the ATL. The mean (SD) of changes in the raw score difference of the neuropsychological tests before and after the ATL was compared between Decline and No-decline groups. Receiver Operating Characteristic curves, sensitivity, specificity, and predictive values were used to assess the optimum cutoff points of neuropsychological test score changes to predict patient-reported subjective cognitive decline. Key findings: Six (12.5%) patients reported a perception of cognitive function decline after ATL. Among the 25 cognitive tests analyzed, only changes in the Boston Naming Test (BNT) were associated with subjective cognitive decline reported by patients. A reduction of points in the raw score of BNT after surgery had 91% of sensitivity and 45% specificity for predicting subjective perception of cognitive function decline by the patient. Left side surgery and age older than 40 years were more associated with an important BNT reduction with overall accuracy of 91.7%, 95% predictive ability for no impairment, and 75% for impairment of cognitive function. Significance: Impairment in word-finding seems to be the objective cognitive finding most relevant to Brazilian patients after mesial temporal lobe epilepsy surgery. Similar to American patients, the side of surgery and age are good predictors for no decline in the BNT, but shows a lower accuracy to predict its decline. If replicated in other populations, the results may have wider implications for the surgical management of patients with drug resistant MTLE. (C) 2017 Elsevier Inc. All rights reserved

Validation of diagnostic tests for depressive disorder in drug-resistant mesial temporal lobe epilepsy

Zingano B de L, Guarnieri R, Diaz AP, et al. Validation of diagnostic tests for depressive disorder in drug-resistant mesial temporal lobe epilepsy. Epilepsy & Behavior. 2015;50:61-66.Purpose: This study aimed to evaluate the diagnostic accuracy of the Hamilton Rating Scale for Depression (HRSD), the Beck Depression Inventory (BDI), the Hospital Anxiety and Depression Scale (HADS), and the Hospital Anxiety and Depression Scale-Depression subscale (HADS-D) as diagnostic tests for depressive disorder in drug-resistant mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). Methods: One hundred three patients with drug-resistant MTLE-HS were enrolled. All patients underwent a neurological examination, interictal and ictal video-electroencephalogram (V-EEG) analyses, and magnetic resonance imaging (MRI). Psychiatric interviews were based on DSM-IV-TR criteria and ILAE Commission of Psychobiology classification as a gold standard; HRSD, BDI, HADS, and HADS-D were used as psychometric diagnostic tests, and receiver operating characteristic (ROC) curves were used to determine the optimal threshold scores. Results: For all the scales, the areas under the curve (AUCs) were approximately 0.8, and they were able to identify depression in this sample. A threshold of >= 9 on the HRSD and a threshold of >= 8 on the HADS-D showed a sensitivity of 70% and specificity of 80%. A threshold of >= 19 on the BDI and HADS-D total showed a sensitivity of 55% and a specificity of approximately 90%. The instruments showed a negative predictive value of approximately 87% and a positive predictive value of approximately 65% for the BDI and HADS total and approximately 60% for the HRSD and HADS-D. Conclusions: HRSD >= 9 and HADS-D >= 8 had the best balance between sensitivity (approximately 70%) and specificity (approximately 80%). However, with these thresholds, these diagnostic tests do not appear useful in identifying depressive disorder in this population with epilepsy, and their specificity (approximately 80%) and PPV (approximately 55%) were lower than those of the other scales. We believe that the BDI and HADS total are valid diagnostic tests for depressive disorder in patients with MTLE-HS, as both scales showed acceptable (though not high) specificity and PPV for this type of study. (C) 2015 Elsevier Inc. All rights reserved

Trends in the prescription of clozapine in a psychiatric hospital: a 5-year observational study

Abstract Introduction Clozapine is a well-recognized effective treatment for some patients with treatment-resistant schizophrenia (TRS). Although it has potential benefits and approximately 30% of patients have a clinical indication for clozapine use, prescription rates are low. Objective To evaluate clozapine prescription trends over a 5-year period in a tertiary psychiatric hospital. Methods In this observational study, data prospectively collected by the Medical and Statistical File Service (Serviço de Arquivo Médico e Estatístico) and the Pharmacy Division of Instituto de Psiquiatria de Santa Catarina between January 2010 and December 2014 were summarized and analyzed by investigators blinded to data collection. The number of 100 mg clozapine pills dispensed by the Pharmacy Division to the inpatient units was the outcome and considered a proxy measure of clozapine prescriptions. The number of occupied inpatient unit beds and the number of patients admitted with F20-F29 (ICD-10) diagnoses during the study period were considered to be possible confounders. Results A multiple linear regression model showed that time in months was independently associated with an increase in the number of clozapine pills dispensed by the Pharmacy Division (β coefficient = 15.82; 95% confidence interval 10.88-20.75). Conclusion Clozapine prescriptions were found to have increased during the 5-year period studied, a trend that is opposite to reports from several other countries