Comparison of 25-hydroxyvitamin D and bilirubin levels between patients with essential tremor and Parkinson's disease / Comparação dos níveis de 25-hidroxivitamina D e bilirrubina entre pacientes com tremor essencial e doença de Parkinson

Introduction: Differential diagnoses between essential tremor and Parkinson's disease is challenging in some individuals, with both disorders sharing similarities. Considering these links, we hypothesized that both conditions have a similar profile for some antioxidant molecules, including 25-hydroxyvitamin D and bilirubin. Methods: We performed a cross-sectional study comparing serum levels of 25-hydroxyvitamin D and bilirubin in 31 ET patients, 38 PD, and 65 controls matched for age. We used the Fahn-Tolosa-Marin scale for the severity of tremors in the ET group. We used Hohen-Yahr and MDS-UPDRS part III scales in the PD group. In addition, we evaluated sociodemographic characteristics, including age, sex, ethnicity, years of study, duration of disease, and use of primidone. Results: We found no differences in serum levels for 25-hydroxyvitamin D or bilirubin subtype levels between the ET and PD groups. We found low levels of indirect bilirubin in the PD group compared to the controls. We did not find differences between ET and controls in all biomarkers of the study. Conclusion: ET and PD patients have similar profiles for 25-hydroxyvitamin D and bilirubin serum levels. The discovery of differences in oxidative stress biomarkers in both conditions, mainly low-cost substances available clinically, can assist in the differential diagnosis and, in the future, prognostication and better therapy management (AU).

Introdução: O diagnóstico diferencial entre tremor essencial (TE) e a doença de Parkinson (DP) é desafiador em alguns indivíduos com ambas as afecções apresentando algumas similaridades. Assim sendo, hipotetizamos que ambas têm perfil similar de algumas moléculas antioxidantes, incluindo 25-hidroxivitamina D e bilirrubina. Méto-dos: Realizamos um estudo transversal comparando os níveis séricos de 25-hidroxivitamina D e bilirrubinas em 31 indivíduos com TE, 38 com DP e 65 controles pareados por idade. A escala de Fahn-Tolosa-Marin foi usada para avaliação da gravidade do tremor no grupo com TE e Hohen-Yahr e UPDRS parte III na avaliação do grupo com DP. Também foram avaliadas as características sociodemográficas. Resultados: Não encontramos diferenças nos níveis séricos de 25-hidroxivitamina D ou bilirrubina entre os grupos TE e DP. Encontramos baixos níveis de bilirrubina indireta no grupo DP comparado aos controles. Não encontramos diferenças entre os grupos com TE e controles em nenhum dos biomarcadores do estudo. Conclusão: Pacientes com TE e DP apresentam níveis séricos semelhantes de 25-Hidroxivitamina D e bilirrubinas. Diferenças nos biomarcadores de estresse oxidativo em ambas as condi-ções, principalmente substâncias de baixo custo disponíveis na clínica, pode auxiliar no diagnóstico diferencial e, futuramente, no prognóstico e otimização terapêutica (AU).

Current applications for magnetic resonance-guided focused ultrasound in the treatment of Parkinson's disease / 中华医学杂志(英文版)

Magnetic resonance-guided focused ultrasound (MRgFUS) is a novel and minimally invasive technology. Since the US Food and Drug Administration approved unilateral ventral intermediate nucleus-MRgFUS for medication-refractory essential tremor in 2016, studies on new indications, such as Parkinson's disease (PD), psychiatric diseases, and brain tumors, have been on the rise, and MRgFUS has become a promising method to treat such neurological diseases. Currently, as the second most common degenerative disease, PD is a research hotspot in the field of MRgFUS. The actions of MRgFUS on the brain range from thermoablation, blood-brain barrier (BBB) opening, to neuromodulation. Intensity is a key determinant of ultrasound actions. Generally, high intensity can be used to precisely thermoablate brain targets, whereas low intensity can be used as molecular therapies to modulate neuronal activity and open the BBB in conjunction with injected microbubbles. Here, we aimed to summarize advances in the application of MRgFUS for the treatment of PD, with a focus on thermal ablation, BBB opening, and neuromodulation, in the hope of informing clinicians of current applications.

Nuevos conceptos en neuromodulación cerebral: rol de DTI y estimulación de tractos / New concepts in brain neuromodulation: role of DTI and tract stimulation

Introducción: La estimulación cerebral profunda es una técnica difundida y validada para eltratamiento de múltiples dolencias neurológicas y psiquiátricas, entre ellas el temblor esencial. Objetivo: Evaluar si existe un correlato clínico-anatómico, para un paciente con TE, entre la mejor estimulación lograda y los tractos involucrados. Para esto se realiza una descripción de la técnica utilizada, incluyendo el procesamiento de imágenes necesario. Material y métodos: Se presenta el caso de un paciente de 53 años de edad, con una historia de 23 años de temblor esencial progresivo e incapacitante. Se realizó un implante de DBS bilateral en Vim. Se realizó un post procesamiento de imágenes con un método desarrollado por nuestro equipo a través del cual se permitió evaluar gráficamente el área de estimulación cerebral y sus relaciones con los tractos implicados en la patología (dento-rubro-talámico, haz piramidal y haz lemniscal). Resultados: El paciente presentó una mejoría del 55% medido por escala de temblor de Tolosa. Se obtuvo una correlación anatómica y funcional de lo esperado según imágenes y la respuesta clínica del paciente. Se constataron efectos adversos cuando la estimulación implicaba fibras del haz piramidal y lemniscal, presentando los mejores efectos clínicos cuando el haz dento-rubro-talámico era influenciado por el área de acción del campo eléctrico. Conclusiones: En este reporte mostramos la aplicabilidad de DTI y tractografía para explicar los efectos de la programación de los pacientes con estimulación cerebral profunda.

Introduction: Deep brain stimulation is a widespread and validated technique for the treatment of multiple neurological and psychiatric disorders, including essential tremor. Objective: To evaluate if there is a clinical-anatomical correlate, for a patient with essential tremor, between the best stimulation achieved and the tracts involved. For this, a description of the technique used is made, including the necessary image processing. Methods: We present the case of a 53-year-old patient with a 23-year history of progressive and disabling essential tremor. A bilateral DBS implant was performed on Vim. We performed a post-processing of images with a method developed by our team through which we were able to graphically evaluate the area of brain stimulation and its relationships with the tracts involved in the pathology (dento-rubro-thalamic tract, pyramidal tract and lemniscal tract). Conclusions: In this report we showed the applicability of DTI and tractography to explain the clinical effects of the programming features in patients with deep brain stimulation.

Temblor de Holmes, como manifestación única o predominante en lesiones cerebelosas de origen vascular / Holmes's Tremor as isolated or predominant manifestation in cerebellar lesions of vascular origin

Resumen El temblor de Holmes o rúbrico es infrecuente de ver como manifestación única o predominante de un accidente vascular encefálico cerebeloso. "Grosso modo" el temblor es un trastorno del movimiento habitual en la practica medica, siendo el fisiológico exacerbado el más frecuentemente visto; y el temblor esencial el más común de los movimientos involuntarios patológicos. Los estudios de neuroimágenes han concluido la importancia del cerebelo y de toda la vía cerebelotalámo-cortical en la patogénesis del temblor en general; sin dilucidar aun todas las estructuras involucradas entre las que se menciona a nivel molecular, las células de Purkinje. El temblor de Holmes es una manifestación extrapiramidal frecuente en lesiones cerebelosas de origen vascular; asociándose habitualmente a otra sintomatología de circulación posterior. Presentamos dos casos de temblor rúbrico o de Holmes como manifestación predominante de accidente vascular encefálico. Los autores concluyen que es posible este tipo de presentación, especialmente en pacientes con temblor de acción de inicio ictal, o en aquellos casos de temblor de reposo no parkinsoniano con mala respuesta a la L-Dopa; y en dichos casos, con lesión no mescencefálica, los pacientes podrían beneficiarse del uso de anticolinérgicos.

Holmes's tremor; or rubric tremor is infrequent as predominantly or unique manifestation of cerebellum stroke. Grosso modo tremor is a movement's disorder common in medical practice, being the physiological exacerbated type the most frequently seen, and the essential tremor the most frequently seen in pathological involuntary movements. Neuroimaging studies have concluded the importance of the cerebellum and of the entire cortical-cerebellar- thalamic pathway in the pathogenesis of tremor in general; without specifically of all the structures involved; but among which is mentioned at the molecular level the Purkinje cells. Holmes's tremor, is one of the frequently extrapyramidal manifestations of cerebellar lesions of vascular origin; and it is common to be associated with another symptomatology of posterior circulation. We present two cases of rubric Holmes tremor, as a predominant manifestation of stroke. The authors conclude that this type of presentation is possible, especially in patients with Holmes tremor with ictal onset, or in those cases of non-parkinsonian resting tremor that responds poorly to L-Dopa; and suggest that in such cases, with non-mesencephalic injury, patients could benefit from the use of anticholinergics.

Análisis semiológico de las manifestaciones atípicas de temblor en pacientes con enfermedad de Parkinson y temblor esencial / Semiological analysis of atypical manifestations of tremor in Parkinson's disease and essential tremor

RESUMEN OBJETIVO: La enfermedad de Parkinson (EP) y el temblor esencial (TE) son las patologías que con más frecuencia presentan temblor como manifestación crucial, no obstante, a pesar de que su fisiopatología, diagnóstico y tratamiento son totalmente distintos. El síntoma de temblor suele acarrear un desafío clínico para su correcto enfoque, lo cual lleva frecuentemente a confusión y subsecuentemente a tratamientos erróneos. En este estudio se pretende caracterizar, individualizar y describir las manifestaciones atípicas del temblor en pacientes con diagnóstico de EP y TE con el objetivo de proporcionar herramientas para aumentar la efectividad del diagnóstico de estas condiciones. METODOLOGÍA: Estudio observacional, de corte transversal, en el cual se describió cada variable por medio de medidas de tendencia central y dispersión para variables cuantitativas y frecuencias absolutas y relativas para las variables categóricas. RESULTADOS: Se encontraron manifestaciones típicas y atípicas para ambas patologías, siendo el temblor en reposo la manifestación atípica más frecuente en TE; se encontró en el 35 % de los pacientes (p = 0,0001). Para la EP, un 40 % de los pacientes presentaron temblor postural (p = 0,001) como manifestación atípica. CONCLUSIONES: Los signos atípicos del temblor en la EP y en el TE deben ser tomados en cuenta al establecer el diagnóstico clínico de ambas patologías, para intentar disminuir la posibilidad de generar un diagnóstico erróneo con un tratamiento inadecuado.

SUMMARY OBJECTIVE: Parkinson's disease (PD) and essential tremor (ET) are the most prevalent pathologies in which tremor is an important symptom. Despite the fact that both conditions exhibit a totally different pathophysiology, diagnosis criteria and treatment, the clinical assessment of this manifestation tends to generate bias and confusion, leading to misdiagnosis and subsequently wrong prescriptions. This study intents to assess both typical and atypical features of PD and ET and provide some insights about the relevance of clinical judgement to provide better treatments. METHODOLOGY: This is an observational cross-sectional study with a sample of 20 PD patients and 20 ET patients. Each variable was described using measure of central tendency and dispersion for quantitative variables and absolute and relative frequencies for categorical ones. RESULTS: Typical and atypical manifestations were found in both pathologies, tremor at rest was the most frequent atypical manifestation in ET presented in 35 %% of patients (p = 0.0001). For PD 40 %% of patients showed postural tremor being the most frequent atypical characteristic (p = 0.001). CONCLUSIONS: Atypical signs in PD and ET must be taken into account to avoid misdiagnosis. The clinical phenomenology of both diseases concerning tremor can overlap, and tremor interpretation can improve patient care.

Magnetic Resonance-Guided Focused Ultrasound : Current Status and Future Perspectives in Thermal Ablation and Blood-Brain Barrier Opening

Magnetic resonance-guided focused ultrasound (MRgFUS) is an emerging new technology with considerable potential to treat various neurological diseases. With refinement of ultrasound transducer technology and integration with magnetic resonance imaging guidance, transcranial sonication of precise cerebral targets has become a therapeutic option. Intensity is a key determinant of ultrasound effects. High-intensity focused ultrasound can produce targeted lesions via thermal ablation of tissue. MRgFUS-mediated stereotactic ablation is non-invasive, incision-free, and confers immediate therapeutic effects. Since the US Food and Drug Administration approval of MRgFUS in 2016 for unilateral thalamotomy in medication-refractory essential tremor, studies on novel indications such as Parkinson's disease, psychiatric disease, and brain tumors are underway. MRgFUS is also used in the context of blood-brain barrier (BBB) opening at low intensities, in combination with intravenously-administered microbubbles. Preclinical studies show that MRgFUS-mediated BBB opening safely enhances the delivery of targeted chemotherapeutic agents to the brain and improves tumor control as well as survival. In addition, BBB opening has been shown to activate the innate immune system in animal models of Alzheimer’s disease. Amyloid plaque clearance and promotion of neurogenesis in these studies suggest that MRgFUS-mediated BBB opening may be a new paradigm for neurodegenerative disease treatment in the future. Here, we review the current status of preclinical and clinical trials of MRgFUS-mediated thermal ablation and BBB opening, described their mechanisms of action, and discuss future prospects.

Skull Factors Affecting Outcomes of Magnetic Resonance-Guided Focused Ultrasound for Patients with Essential Tremor

PURPOSE: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy has become a standard treatment for medically intractable essential tremor (ET). Skull density ratio (SDR) and skull volume in patients with ET are currently considered useful indicators of the successful application of MRgFUS. We compared the clinical outcomes of MRgFUS thalamotomy with SDR above 0.4 and 0.45. We also described patterns of SDR and skull volume in Korean patients with ET who were eligible to be screened for MRgFUS. MATERIALS AND METHODS: In screening 318 ET patients, we evaluated patterns of skull density and skull volume according to age and sex. Fifty patients with ET were treated with MRgFUS. We investigated the effects of SDR and skull volume on treatment parameters and the outcomes of ET. RESULTS: The mean SDR of the 318 ET patients was 0.45±0.11, and that for skull volume was 315.74±40.95 cm³. The male patients had a higher SDR than female patients (p=0.047). Skull volume significantly decreased with aging. SDR and skull volume exhibited a linear negative relationship. Among therapeutic parameters, maximal temperature was positively related to SDR, while sonication number was not related to either SDR or skull volume. Tremor outcome was also not related to SDR or skull volume. CONCLUSION: SDR varied widely from 0.11 to 0.73, and men had a higher SDR. Therapeutic parameters and clinical outcomes were not affected by SDR or skull volume.

Magnetic Resonance-Guided Focused Ultrasound : Current Status and Future Perspectives in Thermal Ablation and Blood-Brain Barrier Opening

Magnetic resonance-guided focused ultrasound (MRgFUS) is an emerging new technology with considerable potential to treat various neurological diseases. With refinement of ultrasound transducer technology and integration with magnetic resonance imaging guidance, transcranial sonication of precise cerebral targets has become a therapeutic option. Intensity is a key determinant of ultrasound effects. High-intensity focused ultrasound can produce targeted lesions via thermal ablation of tissue. MRgFUS-mediated stereotactic ablation is non-invasive, incision-free, and confers immediate therapeutic effects. Since the US Food and Drug Administration approval of MRgFUS in 2016 for unilateral thalamotomy in medication-refractory essential tremor, studies on novel indications such as Parkinson's disease, psychiatric disease, and brain tumors are underway. MRgFUS is also used in the context of blood-brain barrier (BBB) opening at low intensities, in combination with intravenously-administered microbubbles. Preclinical studies show that MRgFUS-mediated BBB opening safely enhances the delivery of targeted chemotherapeutic agents to the brain and improves tumor control as well as survival. In addition, BBB opening has been shown to activate the innate immune system in animal models of Alzheimer’s disease. Amyloid plaque clearance and promotion of neurogenesis in these studies suggest that MRgFUS-mediated BBB opening may be a new paradigm for neurodegenerative disease treatment in the future. Here, we review the current status of preclinical and clinical trials of MRgFUS-mediated thermal ablation and BBB opening, described their mechanisms of action, and discuss future prospects.

Asociación entre temblor esencial y diabetes mellitus: estudio de casos y controles / Association between Essential Tremor and Diabetes Mellitus. A Case-Control Study

RESUMEN INTRODUCCIÓN: El temblor esencial es el temblor más común. No se ha descrito la asociación entre diabetes y temblor esencial. El objetivo de este estudio de casos y controles es documentar la asociación entre diabetes mellitus y temblor esencial. MÉTODOS: Se realizó un estudio de casos y controles en población clínica de pacientes incidentes con temblor esencial, pareados por edad y género, a quienes se les interrogó sobre antecedente de diabetes mellitus. Se determinó el OR mediante regresión logística condicionada. RESULTADOS: Se estudiaron 262 casos de temblor esencial y 262 controles. El antecedente de diabetes mellitus se encontró en 39 casos con temblor esencial y en 24 controles, lo que representa una asociación positiva entre los dos (OR 2,15, IC95 % 1,05 a 4,41). DISCUSIÓN: Este estudio de casos y controles en una población clínica muestra que los pacientes con temblor esencial tienen dos veces más probabilidad de tener el antecedente de diabetes mellitus.

SUMMARY INTRODUCTION: The essential tremor is the most common tremor. It has not been described the association between diabetes and essential tremor. The objective of this case-control study is to document the association between diabetes mellitus and essential tremor. METHODS: It was carried out a case-control study in incident patients of clinical population with essential tremor, paired by age and gender, who they were interrogated the antecedent of diabetes mellitus. The OR was determined by means of conditioned logistical regression. RESULTS: 262 cases of essential tremor and 262 controls were studied. The antecedent of diabetes mellitus was in 39 cases with essential tremor and in 24 controls, with an OR 2.15 (95 %% CI 1.05 to 4.41). DISCUSSION: This case-control study in a clinical population shows that the patients with essential tremor have 2 times more probability of having the antecedent of diabetes mellitus.

Prevalência do tremor essencial em população exposta ocupacionalmente a agrotóxicos no Estado do Rio de Janeiro / Prevalence of essential tremor in occupationally exposed population to pesticides in the State of Rio de Janeiro

Introdução: O tremor essencial é um dos distúrbios de movimento mais frequentes em adultos. Objetivo: Estimar a prevalência de tremor essencial em um grupo de guardas de endemia expostos cronicamente a agrotóxicos, identificar seus municípios de lotação e os principais inseticidas e larvicidas aplicados. Método: Estudo transversal descritivo e inferencial com dados obtidos de prontuários médicos dos guardas de endemias oriundos da Fundação Nacional de Saúde (Funasa), que buscaram atendimento no Ambulatório de Neurotoxicologia Ocupacional e Ambiental do Cesteh/Ensp/Fiocruz no período entre agosto/2010 a setembro/2012. Resultados: Foram analisados 383 registros. A estimativa da prevalência de tremor essencial foi de 14,4% (IC95%: 10,9 - 17,9). Foram identificados 19 municípios de lotação e 12 princípios ativos aplicados. Conclusão: Observou-se elevada prevalência de tremor essencial nesta amostra. Limitações no desenho devem ser consideradas, sendo necessário avaliar seus resultados com cautela. (AU)

Introdution: Essential tremor is one of the most frequent movement disorders in adults. Objective: To estimate the prevalence of essential tremor in a group of public pesticide applicators, identify their counties and the main insecticides and larvicides applied. Method: This is a descriptive and inferential, transversal analysis performed from the secondary data obtained from medical records of public pesticide applicators originated from Fundação Nacional de Saúde (Funasa), seeking care at Outpatient Clinic of Occupational and Environmental Neurotoxicology from Cesteh/Ensp/Fiocruz between august/ 2010 and september/2012. Results: In our sample, the estimate of the prevalence of essential tremor was 14.4 % (95%CI: 10,9 to 17,9), 19 counties and 12 pesticides applied were identified. Conclusion: It was observed a high prevalence of essential tremor, but this result must be treated with caution. (AU)

Magnetic Resonance-Guided Focused Ultrasound in Neurosurgery: Taking Lessons from the Past to Inform the Future

Magnetic resonance-guided focused ultrasound (MRgFUS) is a new emerging neurosurgical procedure applied in a wide range of clinical fields. It can generate high-intensity energy at the focal zone in deep body areas without requiring incision of soft tissues. Although the effectiveness of the focused ultrasound technique had not been recognized because of the skull being a main barrier in the transmission of acoustic energy, the development of hemispheric distribution of ultrasound transducer phased arrays has solved this issue and enabled the performance of true transcranial procedures. Advanced imaging technologies such as magnetic resonance thermometry could enhance the safety of MRgFUS. The current clinical applications of MRgFUS in neurosurgery involve stereotactic ablative treatments for patients with essential tremor, Parkinson's disease, obsessive-compulsive disorder, major depressive disorder, or neuropathic pain. Other potential treatment candidates being examined in ongoing clinical trials include brain tumors, Alzheimer's disease, and epilepsy, based on MRgFUS abilities of thermal ablation and opening the blood-brain barrier. With the development of ultrasound technology to overcome the limitations, MRgFUS is gradually expanding the therapeutic field for intractable neurological disorders and serving as a trail for a promising future in noninvasive and safe neurosurgical care.

Hand Tremor Questionnaire: A Useful Screening Tool for Differentiating Patients with Hand Tremor between Parkinson's Disease and Essential Tremor

BACKGROUND AND PURPOSE: Hand tremor is one of the most frequent symptoms in movement disorders, and differential diagnoses for hand tremor include Parkinson's disease (PD) and essential tremor (ET). However, accurately differentiating between PD and ET in clinical practice remains challenging in patients presenting with hand tremor. We investigated whether a questionnaire-based survey could be useful as a screening tool in patients with hand tremor. METHODS: A questionnaire related to hand tremor consisting of 12 items was prospectively applied to patients with PD or ET in three movement-disorder clinics. Each question was analyzed, and a query-based scoring system was evaluated for differentiating hand tremors between PD and ET. RESULTS: This study enrolled 24 patients with PD and 25 patients with ET. Nine of the 12 questions differed significantly between PD and ET: 1 about resting tremor, 4 questions about action tremor, and 4 about asymmetry. A receiver operating characteristics curve analysis revealed that the 9-item questionnaire showed a good discrimination ability, with a sensitivity of 88% and a specificity of 84%. CONCLUSIONS: The developed Hand Tremor Questionnaire might be a good screening tool for hand tremors in patients with PD and ET.

Tremor essencial em guardas de endemias expostos a agrotóxicos: estudo caso-controle / Essential tremor in endemic disease control agents exposed to pesticides: a case-control study / Temblor esencial en empleados públicos del sector de vigilancia y control de endemias expuestos a pesticidas: estudio caso-control

Resumo: Tremor é o distúrbio do movimento mais frequente na população, e pode estar associado a exposição a agrotóxicos. O objetivo foi avaliar a chance de tremor essencial em 442 guardas de endemias do Estado do Rio de Janeiro, Brasil, expostos a agrotóxicos. Foram selecionados 51 casos e 204 controles (1:4). Todos os participantes responderam a um questionário sobre aspectos sociodemográficos, ocupacionais e toxicológicos. A influência da exposição a agrotóxicos sobre o desenvolvimento do tremor foi estimada por regressão logística não condicional, ajustada por covariáveis selecionadas. A idade média da população estudada foi de 49 (DP = 7) anos, sendo a diferença entre casos (média = 50,8; DP = 6,9) e controles (média = 48,5; DP = 6,9) estatisticamente significativa (p = 0,03). Além disso, aqueles com 16 a 16,9 anos de aplicação de agrotóxicos foram os que estiveram sob maior chance de apresentar a doença (OR ajustada = 4,60; IC95%: 1,29-16,41). Nossos resultados sugerem que o período entre 16 e 16,9 anos de aplicação de agrotóxicos teve impacto importante para o desenvolvimento dessa doença.

Abstract: Tremor is the most frequent movement disorder in the population and can be associated with pesticide exposure. The aim was to assess the odds of essential tremor in 442 endemic disease control agents in Rio de Janeiro State, Brazil, exposed to pesticides. Fifty-one cases and 204 controls were selected (1:4). All participants answered a questionnaire on socio-demographic, occupational, and toxicological items. The influence of pesticide exposure on the development of tremor was estimated by non-conditional logistic regression, adjusted for selected covariables. Mean age of the study population was 49 (SD = 7) years, and the difference between cases (mean = 50.8; SD = 6.9) and controls (mean = 48.5; SD = 6.9) was statistically significant (p = 0.03). Those with 16 to 16.9 years of pesticide use showed the highest odds of essential tremor (adjusted OR = 4.60; 95%CI: 1.29-16.41). Our results suggest that 16 to 16.9 years of pesticide exposure had a major impact on the development of essential tremor.

Resumen: El temblor es el disturbio de movimiento más frecuente en la población y puede estar asociado a la exposición a pesticidas. El objetivo fue evaluar la oportunidad del temblor esencial en 442 empleados públicos del sector de endemias del estado de Río de Janeiro, Brasil, expuestos a pesticidas. Se seleccionaron 51 casos y 204 controles (1:4). Todos los participantes respondieron a un cuestionario sobre aspectos sociodemográficos, ocupacionales y toxicológicos. La influencia de la exposición a pesticidas sobre el desarrollo del temblor fue estimada por regresión logística no condicional, ajustada por covariables seleccionadas. La edad media de la población estudiada fue de 49 (DP = 7) años, siendo la diferencia entre casos (media = 50,8; DP = 6,9) y controles (media = 48,5; DP = 6,9) estadísticamente significativa (p = 0,03). Además, aquellos de 16 a 16,9 años de servicio de fumigación con pesticidas fueron los que estuvieron bajo la mayor oportunidad de presentar la enfermedad (OR ajustada = 4,60; IC95%: 1,29-16,41). Nuestros resultados sugieren que el período entre 16 y 16,9 años de fumigación con pesticidas tuvo un impacto importante para el desarrollo de esa enfermedad.

Comorbilidades y alteración de la calidad de vida en pacientes adultos con temblor esencial / Comorbidities and altered quality of life in adult patients with essential tremor

Introducción: El temblor esencial constituye el trastorno de movimiento más frecuente, se caracteriza por un temblor cinético postural de 4-12 Hz de frecuencia. Es una enfermedad crónica, progresiva y neurodegenerativa que tiene una repercusión heterogénea sobre la calidad de vida. Materiales y métodos: Se analizó la presencia de comorbilidades aplicando el índice de Charlson corregido, se valoró la correlación de estas patologías sobre la calidad de vida, ámbito emocional y funcionalidad de pacientes con temblor esencial. Resultados: Se estudiaron 132 pacientes con temblor esencial y no se encontró una correlación significativa entre la presencia de ansiedad, depresión y el estado cognitivo con la calidad de vida de éstos pacientes. Discusión: Las comorbilidades, medidas con el índice de Charlson, no se correlacionan con la calidad de vida y sus distintas esferas en pacientes con temblor esencial.

Introduction: Essential tremor is the most frequent movement disorder, is characterized as a postural tremor of 4-12 Hz frequency. Is a chronic, progressive and neurodegenerative disease that has a heterogeneous impact on quality of life, considering that it is a prevalent disease in older adults who have comorbidities aging, it is necessary to determine to what extent these comorbidities affect different areas of quality of life. Methods: The presence of comorbidities were analyzed using the Charlson index adjusted for age, focused on the relation of these comorbidities with the quality of life, emotional scope and functionality of patients with essential tremor. Results: One hundred and thirty two patientes with essential tremor were studied. We did not find a significant correlation between the presence of anxiety, depression and cognitive status with the quality of life of these patients. Discusion: Comorbidities assessed by the Charlson index do not correlate with quality of life in patients with essential tremor.

Focused ultrasound treatment for central nervous system disease: neurosurgeon's perspectives

The concept of focused ultrasound (FUS) and its application in the field of medicine have been suggested since the mid-20th century. However, the clinical applications of this technique in central nervous system (CNS) diseases have been extremely limited because the skull inhibits efficient energy transmission. Therefore, early application of FUS treatment was only performed in patients who had already undergone invasive procedures including craniectomy and burr hole trephination. In the 1990s, the phased array technique was developed and this enabled the focus of ultrasonic energy through the skull, and in conjunction with another technique, magnetic resonance thermal monitoring, the possibility of applying FUS in the CNS was further strengthened. The first clinical trial using FUS treatment for CNS diseases was performed in the early 21(st) century in patients with glioblastoma, which consists of highly malignant primary brain tumors. However, this trial resulted in a failure to make lesions in the tumors. Various causes were suggested for this outcome including different acoustic impedances across heterogeneous intracranial tissue (not only brain tissue, but also fibrous or tumor tissue). To avoid the influence of this factor, the targets for FUS treatment were shifted to functional diseases such as essential tremor, Parkinson's disease, and psychiatric disease, which usually occur in normal brain structures. The first trial for functional diseases was started in 2010, and the results were successful as accurate lesions were made in the target area. Nowadays, the indication of FUS treatment for functional CNS diseases is gradually widening, and many trials using the FUS technique are reporting good results. In addition to the lesioning technique using high intensity FUS treatment, the possibility of clinical application of low intensity FUS to CNS disease treatment has been investigated at a preclinical level, and it is expected that FUS treatment will become one of the most important novel techniques for the treatment of CNS diseases in the near future.

TeleCondutas: tremor e síndromes parkinsonianas / TeleGuides: tremor and parkinsonian syndromes

As principais causas de tremor em pacientes atendidos na Atenção Primária à Saúde são: exacerbação de tremor fisiológico, tremor essencial (acomete 5% da população acima de 40 anos) e as síndromes parkinsonianas. É importante definir corretamente sua origem, pois o tratamento e o prognóstico são variados. Esta guia apresenta informação que orienta a conduta para casos de tremor e síndromes parkinsonianas no contexto da Atenção Primária à Saúde, incluindo: etiologia do tremor e síndromes parkinsonianas, avaliação clínica, tipos de tremor, sintomas cardinais de parkinsonismo, medicamentos indutores, fluxograma de avaliação do tremor, exames complementares, tratamento do tremor essencial e doença de parkinson, encaminhamento para serviço especializado.

Progress in genetic research on essential tremor / 中华医学遗传学杂志

Essential tremor (ET) is one of the most common movement disorders. Its clinical manifestations not only include typical kinetic and/or postural tremors, but also other non-motor symptoms such as cognitive dysfunction, sleep disturbance, and dysosmia. The exact etiology and pathogenesis of ET is still unknown. Approximately 60% of ET patients have a family history, and genetic factor plays an important role in the onset of the disease. Researchers have so far identified 3 genetic loci (ETM 1-3) through family studies, and proposed additional causative genes such as FUS, HTRA2, TENM4, NOS3 and susceptibility genes such as LINGO, SLC1A2, and GABA. This review focuses on the progress made in genetic research on ET.

Temblores posanestésicos / Post-anesthetic shivering

Introducción: los temblores posanestésico son causa de una de las mayores insatisfacciones durante el posoperatorio inmediato. Es un fenómeno frecuente, potencialmente perjudicial por aumentar la demanda metabólica de oxígeno. Objetivo: hacer una actualización sobre los temblores Posanestésicos y su profilaxis. Métodos: constituyen una actividad muscular oscilatoria para aumentar la producción de calor. Su etiología es desconocida, aunque se le atribuyen numerosas causas. Su frecuencia oscila entre 6,3 y 66 por ciento. De 5 a 65 por ciento relacionadas con anestesia general y 30 por ciento con anestesia regional. Con anestesia general, la temperatura central disminuye entre 0,5 y 1,5 °C, en la primera hora posterior a la inducción, al igual que en la anestesia regional. Este mecanismo se produce por redistribución del calor del centro a la periferia. Todos los anestésicos, opioides y sedantes disminuyen la vasoconstricción y el control autonómico de la regulación térmica y facilitan la hipotermia. Se presenta con mayor frecuencia en pacientes jóvenes, del sexo masculino, en los cuales se administraron agentes anestésicos halogenados, con tiempo anestésico quirúrgico prolongado. Numerosos artículos señalan, que en las especies homeotérmicas se presenta un sistema termorregulador que coordina la defensa contra la temperatura ambiental, para mantener la temperatura interna en un umbral estrecho. La combinación de agentes inductores anestésicos y exposición al ambiente frío hacen que los pacientes presenten temblores posanestésicos. Su profilaxis está dada por el uso de meperidina, clonidina y tramadol. La ketamina, es una fenciclidina, que produce disociación electrofisiológica entre los sistemas límbico y cortical. Se une a dos dianas moleculares en el encéfalo: las terminaciones dopaminérgicas en el núcleo accumbens y los receptores de N-metil de aspartato. Cuando la ketamina se une a dichos receptores, inhibe la liberación de dopamina. Conclusiones: los temblores Posanestésicos constituyen un efecto adverso de la anestesia que pueden ser evitados. La ketamina, por su mecanismo de acción parece jugar un papel en su profilaxis, pues al bloquear dicho receptor se infiere que es posible que module, en alguna medida, la regulación térmica en varios niveles(AU)

Introduction: post-anesthetic shivering is caused by one of the greatest dissatisfactions during the immediate postoperative period. It is a common event, also potentially damaging because it increases the metabolic demand for oxygen. Objective: To make an update on post-anesthetic shivering and its prophylaxis. Methods: It constitutes an oscillatory muscle activity to increase heat production. Its etiology is unknown, although it is attributed to many causes. Its frequency varies between 6.3 and 66 percent. 5 to 65 percent are related to general anesthesia, and 30 percent to regional anesthesia. Under general anesthesia, the central temperature decreases from 0.5 to 1.5 °C in the first hour after induction, as in regional anesthesia. This mechanism is caused by redistribution of heat from the center to the periphery. All anesthetics, opioids and sedatives decrease vasoconstriction and the autonomic control of thermal regulation, and facilitate hypothermia. It occurs most often in young patients, male, to whom halogenated anesthetic agents are administered with anesthetic prolonged surgical time. Many items indicate that in the homeothermic species a thermoregulator system is present, which coordinates the defense against the environmental temperature to maintain the internal temperature in a narrow threshold. The combination of anesthetic inducing agents and exposure to cold environment make patients present post-anesthetic shivering. Prophylaxis is attained by using meperidine, clonidine and tramadol. Ketamine is a phencyclidine, which produces electrophysiological dissociation between the limbic and cortical systems. It is bound to two molecular targets in the brain: dopaminergic terminals in the accumbens nucleus and the N-methyl aspartate receptor. When ketamine binds to these receptors, it inhibits the release of dopamine. Conclusions: Post-anesthetic shivering constitutes an adverse effect of anesthesia, which can be avoided. Ketamine, for its action mechanism, seem to play a role in prevention, because when such receptor is blocked, it is inferred to module, at some extent, thermal regulation at various levels(AU)

Patients with essential tremor can have manual dexterity and attention deficits with no impairments in other cognitive functions / Pacientes com tremor essencial podem apresentar prejuízo na destreza manual e déficit de atenção sem prejuízo em outras áreas da cognição

ABSTRACT Essential tremor (ET) was long believed to be a monosymptomatic disorder. However, studies have evidenced structural changes and attention is now being focused on non-motor symptoms. The objective of the study is to describe and compare ET patients with control groups according to their cognitive functions, and secondarily, to compare their sociodemographic characteristics and other clinical features. All participants were assessed using the Fahn-Tolosa-Marin Tremor Rating Scale for the severity of tremor; a neuropsychological assessment battery and a screening questionnaire for mood and anxiety symptoms. There were no significant age and gender differences between all groups. As for neuropsychological assessment results, a significant difference was found only in the Pegboard test. We also found a significant negative correlation between a poorer cognitive test results and disease severity and a significant differences regarding depression or anxiety symptoms in patients with ET. The study results suggest that patients with ET have impaired manual dexterity and attention.

RESUMO O tremor essencial (TE) era considerado como um transtorno monossintomático. Contudo estudos tem demonstrado alterações anatômicas despertando o interesse para sintomas não-motores.O objetivo do estudo é descrever e comparar pacientes com grupos controles segundo suas funções cognitivas, e secundariamente, comparar suas características demográficas e outros sintomas clínicos. Todos os participantes foram submetidos à escala de Fahn, Tolosa e Marin para avaliação da intensidade do tremor, a uma bateria neuropsicológica e a um questionário para detecção de transtorno de humor e ansiedade. Não houve diferença significativa na idade e gênero entre todos os grupos. Quanto ao resultado da avaliação neuropsicológica, foi encontrado uma diferença significativa apenas no Test Pegboard. Nós também encontramos uma correlação negativa no desempenho dos testes cognitivos e intensidade do tremor, presença de sintomas depressivos e ansiosos. Os resultados deste trabalho sugerem que pacientes com TE apresentem alteração na destreza manual e na atenção.

Laryngoscopy evaluation protocol for the differentiation of essential and dystonic voice tremor / Protocolo de avaliação por laringoscopia para diferenciar tremor vocal essencial e distônico

ABSTRACT INTRODUCTION: Although syndromes that cause voice tremor have singular characteristics, the differential diagnosis of these diseases is a challenge because of the overlap of the existing signs and symptoms. OBJECTIVE: To develop a task-specific protocol to assess voice tremor by means of nasofibrolaryngoscopy and to identify those tasks that can distinguish between essential and dystonic tremor syndromes. METHODS: Cross-sectional study. The transnasal fiberoptic laryngoscopy protocol, which consisted of the assessment of palate, pharynx and larynx tremor during the performance of several vocal and non-vocal tasks with distinct phenomenological characteristics, was applied to 19 patients with voice tremor. Patients were diagnosed with essential or dystonic tremor according to the phenomenological characterization of each group. Once they were classified, the tasks associated with the presence of tremor in each syndrome were identified. RESULTS: The tasks that significantly contributed to the differential diagnosis between essential and dystonic tremor were /s/ production, continuous whistling and reduction of tremor in falsetto. These tasks were phenomenologically different with respect to the presence of tremor in the two syndromes. CONCLUSION: The protocol of specific tasks by means of transnasal fiberoptic laryngoscopy is a viable method to differentiate between essential and dystonic voice tremor syndromes through the following tasks: /s/ production, continuous whistling and reduction of tremor in falsetto.

RESUMO INTRODUÇÃO: Apesar de haver características próprias entre as síndromes causadoras do tremor vocal, o diagnóstico diferencial destas doenças é um desafio pela sobreposição de sinais e sintomas presentes. OBJETIVO: Desenvolver protocolo de tarefas específicas na avaliação do tremor vocal por nasofibrolaringoscopia e identificar aquelas que diferenciem as síndromes de tremor essencial e distônico. MÉTODO: Estudo transversal. O protocolo de nasofibrolaringoscopia, que consistiu na avaliação do tremor em palato, faringe e laringe durante execução de diversas tarefas fonatórias e não-fonatórias com características fenomenológicas distintas, foi aplicado em 19 pacientes com tremor vocal. Os pacientes foram diagnosticados como tremor essencial ou distônico a partir da caracterização fenomenológica de cada grupo. Uma vez classificados, determinou-se quais tarefas estavam associadas à presença de tremor nas diferentes síndromes. RESULTADOS: As tarefas que contribuíram significativamente na distinção do tremor essencial e distônico foram a emissão /s/, assobio contínuo e redução do tremor no agudo, pois apresentaram-se fenomenologicamente diferentes quanto à presença do tremor entre as duas síndromes. CONCLUSÃO: O protocolo de tarefas específicas por nasofibrolaringoscopia é um método viável para diferenciar as síndromes de tremor vocal essencial e distônico por meio das tarefas: emissão /s/, assobio contínuo e redução do tremor no agudo.