Missense mutations in TENM4, a regulator of axon guidance and central myelination, cause essential tremor.

Essential tremor (ET) is a common movement disorder with an estimated prevalence of 5% of the population aged over 65 years. In spite of intensive efforts, the genetic architecture of ET remains unknown. We used a combination of whole-exome sequencing and targeted resequencing in three ET families. In vitro and in vivo experiments in oligodendrocyte precursor cells and zebrafish were performed to test our findings. Whole-exome sequencing revealed a missense mutation in TENM4 segregating in an autosomal-dominant fashion in an ET family. Subsequent targeted resequencing of TENM4 led to the discovery of two novel missense mutations. Not only did these two mutations segregate with ET in two additional families, but we also observed significant over transmission of pathogenic TENM4 alleles across the three families. Consistent with a dominant mode of inheritance, in vitro analysis in oligodendrocyte precursor cells showed that mutant proteins mislocalize. Finally, expression of human mRNA harboring any of three patient mutations in zebrafish embryos induced defects in axon guidance, confirming a dominant-negative mode of action for these mutations. Our genetic and functional data, which is corroborated by the existence of a Tenm4 knockout mouse displaying an ET phenotype, implicates TENM4 in ET. Together with previous studies of TENM4 in model organisms, our studies intimate that processes regulating myelination in the central nervous system and axon guidance might be significant contributors to the genetic burden of this disorder.

Interaction between sex and neurofilament light chain on brain structure and clinical severity in Huntington's disease.

Female Huntington's disease (HD) patients have consistently shown a faster clinical worsening than male, but the underlying mechanisms responsible for this observation remain unknown. Here, we describe how sex modifies the impact of neurodegeneration on brain atrophy and clinical severity in HD. Cerebrospinal fluid neurofilament light chain (NfL) levels were used as a biological measure of neurodegeneration, and brain atrophy was assessed by structural magnetic resonance imaging. We found that larger NfL values in women reflect higher brain atrophy and clinical severity than in men (p < 0.05 for an interaction model). This differential vulnerability could have important implications in clinical trials.

Alterations in cerebral white matter and neuropsychology in patients with cirrhosis and falls.

BACKGROUND & AIM: Falls are frequent in patients with cirrhosis but underlying mechanisms are unknown. The aim was to determine the neuropsychological, neurological and brain alterations using magnetic resonance-diffusion tensor imaging (MR-DTI) in cirrhotic patients with falls. PATIENTS AND METHODS: Twelve patients with cirrhosis and falls in the previous year were compared to 9 cirrhotic patients without falls. A comprehensive neuropsychological and neurological evaluation of variables that may predispose to falls included: the Mini-Mental State Examination, Psychometric Hepatic Encephalopathy Score (PHES), Parkinson's Disease-Cognitive Rating Scale, specific tests to explore various cognitive domains, Unified Parkinson's Disease Rating Scale to evaluate parkinsonism, scales for ataxia and muscular strength, and electroneurography. High-field MR (3T) including DTI and structural sequences was performed in all patients. RESULTS: The main neuropsychological findings were impairment in PHES (p = 0.03), Parkinson's Disease-Cognitive Rating Scale (p = 0.04) and in executive (p<0.05) and visuospatial-visuoconstructive functions (p<0.05) in patients with falls compared to those without. There were no statistical differences between the two groups in the neurological evaluation or in the visual assessment of MRI. MR-DTI showed alterations in white matter integrity in patients with falls compared to those without falls (p<0.05), with local maxima in the superior longitudinal fasciculus and corticospinal tract. These alterations were independent of PHES as a covariate and correlated with executive dysfunction (p<0.05). CONCLUSIONS: With the limitation of the small sample size, our results suggest that patients with cirrhosis and falls present alterations in brain white matter tracts related to executive dysfunction. These alterations are independent of PHES impairment.

[Dopaminergic treatment in Parkinson's disease: what has each therapeutic family got to offer?]. / Tratamiento dopaminérgico en la enfermedad de Parkinson: ¿qué puede ofrecer cada familia terapéutica?

Different families of dopaminergic agents have allowed to increase the availability of dopamine within the central nervous system by different mechanisms of action. Each drug family has specific efficacious properties, as well as a different profile of adverse events. The knowledge in detail of these specificities is mandatory to avoid severe systemic or neuropsychiatric complications. Despite these limitations, the development of new drugs within the past 20 years has prolonged survival in Parkinson's disease, increasing the time with preserved daily day functionality compared with the levodopa era, when this drug was the only dopaminergic drug available. The correct combination of dopaminergic drugs with different mechanisms of action allows the management of Parkinson's disease motor symptoms within safety dose ranges, and up to day, this appears as the best algorithm to maintain functionality for longer periods of time.

TITLE: Tratamiento dopaminergico en la enfermedad de Parkinson: que puede ofrecer cada familia terapeutica?Diferentes familias de farmacos dopaminergicos han permitido aumentar el suministro de dopamina en el estriado por diferentes mecanismos. Cada familia de farmacos posee un grado de eficacia determinado, asi como un perfil de efectos secundarios especifico que debe conocerse en detalle para evitar complicaciones sistemicas y neuropsiquiatricas graves. A pesar de estas limitaciones, la disponibilidad de multiples farmacos ha permitido aumentar la supervivencia media en la enfermedad de Parkinson, con un periodo de funcionalidad en el dia a dia significativamente mas largo al que se conseguia cuando la levodopa era practicamente el unico farmaco disponible. La correcta adicion de farmacos dopaminergicos con diferentes mecanismos de accion permite tratar la enfermedad de Parkinson sin tener que llegar a dosis excesivamente altas de ninguno de ellos, lo que parece, en el momento actual, el mejor algoritmo para el control de los sintomas motores durante un periodo lo mas duradero posible.

'Apuntes en Neurología': una síntesis de la evidencia en trastornos neurológicos comunes paroxísticos y en trastornos neurodegenerativos / 'Apuntes en Neurología' (Notes in Neurology): a synthesis of the evidence on common paroxysmal neurological disorders and on neurodegenerative disorders

Apuntes en Neurología' es una iniciativa en la cual líderes de primera línea nacional e internacional, con amplio reconocimiento académico, se reunieron para sintetizar los aspectos clínicos más destacables dentro de su área de interés y acercar las novedades en una lengua más próxima. Entender los factores que afectan al inicio y progresión de cualquier enfermedad neurológica a través de una revisión es importante para el desarrollo de estrategias en pro de reducir la carga de estas enfermedades, y conocer los aspectos clínicos es esencial para poder resolver los problemas de la practica clínica diaria. Los datos aquí recogidos reflejan el peso de la evidencia y algunos de ellos anticipan un futuro prometedor en el tratamiento de estas enfermedades. Esta primera edición se centra en trastornos neurológicos comunes paroxísticos como la migraña, la epilepsia y las alteraciones del sueño, y en trastornos neurodegenerativos como la enfermedad de Parkinson y el deterioro cognitivo. Se trata de patologías claramente diferentes, si bien algunas de ellas, como la migraña y la epilepsia, pueden compartir sintomatología clínica. Los trastornos del sueño, por su parte, son manifestaciones importantes de enfermedades neurodegenerativas que, en ocasiones, son clínicamente evidentes mucho antes del inicio de otros síntomas neurológicos. Tras recordar la fisiopatología y el diagnostico, la revisión actual se centra en acercar los principales avances en cinco de las principales enfermedades neurológicas

Introduction. 'Apuntes en Neurologia' is an initiative in which prominent national and international leaders, with broad academic recognition, came together to synthesise the most outstanding clinical aspects within their area of interest and to discuss the latest developments in a more accessible language. Understanding the factors that affect the onset and progression of any neurological disease through a review is important to be able to develop strategies to reduce the burden of these diseases. Moreover, knowledge of the clinical aspects is essential to solve the problems of daily clinical practice. The data collected here reflect the weight of evidence and some of them anticipate a promising future in the treatment of these diseases. This first edition focuses on common paroxysmal neurological disorders such as migraine, epilepsy and sleep disorders, as well as neurodegenerative disorders such as Parkinson' disease and cognitive impairment. These are clearly different pathologies, although some of them such as migraine and epilepsy, may share clinical symptoms. Sleep disorders, however, are important manifestations of neurodegenerative diseases that are sometimes clinically apparent long before the onset of other neurological symptoms. After recalling pathophysiology and diagnosis, the current review focuses on bringing together the main advances in five of the major neurological diseases

[Candidate patient for treatment with continuous apomorphine infusion]. / Paciente candidato a tratamiento con apomorfina en infusión continua.

Subcutaneous apomorphine infusion has been shown to be effective in reducing motor fluctuations and, to a lesser extent, also the levodopa induced dyskinesias in patients with advanced Parkinson's disease (PD). Based on the literature data, the following article reviews the clinical features of PD patients in order to be considered candidates for this therapy. In general, the vast majority of patients with advanced PD can benefit from this therapy and the authors' experience suggests that it should be considered as soon as the conventional pharmacological therapy fails to significantly reduce the number of daily off hours.

[Descriptive analysis of the activity in a movement disorder unit in a tertiary hospital in Catalonia]. / Análisis descriptivo de la actividad de una unidad de trastornos del movimiento en un hospital terciario de Cataluña.

INTRODUCTION: Movement disorders are an important part of the activity of a Neurology service, but there are few studies examining their health care demand. AIMS: To analyze the first visits of the Movement Disorders Unit of the Hospital de la Santa Creu i Sant Pau in Barcelona and to compare the results with those of previous studies. PATIENTS AND METHODS: Prospective study of the first neurological assessments carried out during 2010. Demographic variables of patients were collected and diagnoses were reviewed 12 months later. RESULTS: 423 first visits were done (application rate of 1.41 per 1000 inhabitants-year): 54% females, median age 68.8 ± 14.2 years-old. 74.3% of referrals came from the family doctor. The most frequent reasons for consultation were tremor (40%) and parkinsonism-motor clumsiness (26%). The most prevalent diagnoses were Parkinson's disease (36%) and essential tremor (19%). After the first assessment, 84% of patients continued controls in the Unit. One year later, in the 8% of cases there was a change in the initial diagnosis. Taking into account the incidence of each disorder, the number of patients seen was fewer compared to the estimated (19.5 times lower), especially marked in cases of restless legs syndrome, essential tremor and Tourette syndrome. CONCLUSIONS: In our Unit the most frequent reason for consultation is tremor and the most prevalent diagnosis is Parkinson's disease. The number of patients treated is clearly lower than the estimated according to the incidence of the diseases in the population.

[Rasagiline: effectiveness and protection in Parkinson's disease]. / Rasagilina: eficacia y proteccion en la enfermedad de Parkinson.

INTRODUCTION: Parkinson's disease (PD) is the second most frequent neurodegenerative disease in the general population after Alzheimer's disease. Its diagnosis is based on the presence of characteristic motor symptoms due to the striatal dopaminergic depletion caused by progressive neuronal death in the pars compacta substantiae nigrae. Thus, not only is it necessary to restore the neurochemical deficits that are present from the initial phases of the disease onwards, but therapeutic strategies also need to be developed to stop the degenerative process. DEVELOPMENT: Rasagiline is a monoamine oxidase-B inhibitor whose dopaminergic stimulation has proved to be effective in monotherapy or in combined therapy for improving the motor symptoms in patients with PD in the initial and advanced phases. Likewise, it is also effective in diminishing motor fluctuations. CONCLUSIONS: Comparatively, rasagiline has proved to be at least as effective as entacapone in the control of motor fluctuations. With regard to the possible effect and the neuroprotective properties of rasagiline in vitro and in vivo, it is the first pharmaceutical to have displayed a change in the developmental course of PD after 72 weeks' treatment.

Cardiac (123)I-metaiodobenzylguanidine imaging allows early identification of dementia with Lewy bodies during life.

PURPOSE: Differential diagnosis between dementia with Lewy bodies (DLB) and other neurodegenerative diseases with cognitive impairment represents a clinical challenge. Due to the overlapping of symptoms, the clinical diagnosis can be modified during the prolonged follow-up of these diseases. The purpose of this study was to assess the ability of cardiac metaiodobenzylguanidine (MIBG) imaging for early identification of DLB. MATERIALS AND METHODS: Since January 2003, all patients with neurodegenerative diseases with cognitive impairment at their first visit at the Memory Unit and clinical criteria of DLB were consecutively recruited and underwent a cardiac (123)I-MIBG study. The heart-to-mediastinum ratio (HMR) and the washout rate (WR) of cardiac MIBG uptake were obtained. RESULTS: Sixty-five patients were included. After a clinical follow-up of 4 years, the progress of the disease procured a definite diagnosis in 44 (68%) patients: 19 DLB, 12 Alzheimer disease (AD), and 13 other neurodegenerative diseases with cognitive impairment. HMR was significantly decreased in DLB with respect to the other neurodegenerative diseases. WR was only significantly different between DLB and AD. The HMR cut off point of 1.36 differentiated DLB from the other dementias with a sensitivity of 94% and a specificity of 96% with an accuracy of 95%. CONCLUSIONS: Cardiac MIBG imaging performed at the time of the first clinical diagnosis of DLB can help early clinical identification or exclusion of this disease.

Safinamida desde la práctica clínica diaria: primeros pasos clínicos / Safinamide from daily clinical practice: first clinical steps

Introducción. El tratamiento de complicaciones motoras en la enfermedad de Parkinson (EP) sigue siendo limitado. La safinamida, un nuevo fármaco con actividad inhibidora de la monoaminooxidasa-B y antiglutamatérgica al inhibir canales de sodio, ha mostrado eficacia en dosis de 50-100 mg/día para las fluctuaciones en la EP. Pacientes y métodos. Desde la práctica clínica diaria, se ha descrito la eficacia y la tolerabilidad de la safinamida a los tres meses en pacientes con EP y complicaciones motoras. Se evaluó la eficacia mediante la escala global de impresión de cambio y el cambio en el número de horas en off al día, y se registraron todos los efectos secundarios comunicados por los pacientes. Resultados. En una muestra de 50 pacientes, el 57,4% refirió estar mucho mejor o moderadamente mejor a los tres meses, y presentaba mejoría de las fluctuaciones motoras y no motoras. El tiempo off diario disminuyó significativamente (0,9 ± 0,6 h). En 13 pacientes (27,6%) se redujo la dosis equivalente de levodopa en 132 mg/día. En pacientes con discinesias, la dosis de 100 mg/día consiguió un mejor control de las complicaciones motoras. El 19% de los pacientes presentó efectos secundarios leves. Siete pacientes abandonaron el tratamiento por síndrome confusional. Conclusiones. El mecanismo de acción dopaminérgico y no dopaminérgico de la safinamida permite un buen control de las fluctuaciones en la EP. La presencia de discinesias aconseja usar la safinamida en dosis de 100 mg/día. La safinamida presenta buena tolerabilidad global, pero debe administrarse con cautela en pacientes mayores de 75 años o estadios más avanzados de la enfermedad (AU)

Introduction. The management of motor complications in Parkinson’s disease (PD) is still limited. Safinamide, a new drug that has MAO-B inhibition and antiglutamatergic effects through inhibition of sodium channels, has shown efficacy for the treatment of fluctuations at doses of 50-100 mg/day. Patients and methods. From daily clinical practice, we describe the efficacy and tolerability of safinamide at three months in PD patients with motor complications. Efficacy was assessed by the Clinical Global Impression of Change scale and change in ‘off’ time during the daytime. All reported adverse events were recorded. Results. Fifty patients were recruited. 57.4% reported to be much better or moderately better at three months, improving both motor and non-motor fluctuations. Significant decrease of 0.9 ± 0.6 h/day was achieved at three months. In 13 patients (27.6%), levodopa equivalent daily dose was reduced in 132 mg/day. In patients with dyskinesias, safinamide 100 mg/day was better for controlling fluctuations and dyskinesias. 19% of patients had mild adverse events. Seven patients stopped treatment after development of confusional syndrome. Conclusions. The dopaminergic and non-dopaminergic action of safinamide exerts a good control of motor fluctuations. In patients with fluctuations and dyskinesias the dose of 100 mg/day of safinamide is preferred. Tolerability was good, except for patients older than 75 years or in advanced stages of the disease (AU)

Usefulness of an intraoperative electrophysiological navigator system for subthalamic nucleus surgery in Parkinson's disease.

OBJECTS: The characteristics and benefits are presented of an intraoperative neurophysiological navigator computerized system developed in our center (Columbus-Track 1.0) that helps the surgical team in neuronal identification and in strategy processes in subthalamic nucleus surgery for Parkinson's disease (PD). METHODS: The navigator consists of three assembled parts: (1) neuronal identification, based on wavelet processing, filtering and gaussian characteristics of the signal; (2) track identification, based on anatomical coincidence, somatomotor response and microstimulation quotient, and (3) strategy, coordinating correction for the next track. A retrospective comparative study was performed with 15 consecutive PD patients (30 targets) operated without the system and the next 15 consecutive patients operated with the aid of the system. With the aid of the computerized navigation system, a significant reduction in the number of tracks was observed (t = -2.503, p = 0.0015), with a mean difference of 1.2 tracks per hemisphere. A non-significant reduction in the total intervention time was also observed, with a mean difference of 20 min per hemisphere (t = -1.418, p = 0.161). CONCLUSIONS: The intraoperative computerized navigation system can aid the surgical team in better identifying the neuronal signal and in defining the optimal track to achieve the target.

Tratamiento dopaminérgico en la enfermedad de Parkinson: ¿qué puede ofrecer cada familia terapéutica? / Dopaminergic treatment in Parkinson’s disease: what has each therapeutic family got to offer?

Diferentes familias de fármacos dopaminérgicos han permitido aumentar el suministro de dopamina en el estriado por diferentes mecanismos. Cada familia de fármacos posee un grado de eficacia determinado, así como un perfil de efectos secundarios específico que debe conocerse en detalle para evitar complicaciones sistémicas y neuropsiquiátricas graves. A pesar de estas limitaciones, la disponibilidad de múltiples fármacos ha permitido aumentar la supervivencia media en la enfermedad de Parkinson, con un periodo de funcionalidad en el día a día significativamente más largo al que se conseguía cuando la levodopa era prácticamente el único fármaco disponible. La correcta adición de fármacos dopaminérgicos con diferentes mecanismos de acción permite tratar la enfermedad de Parkinson sin tener que llegar a dosis excesivamente altas de ninguno de ellos, lo que parece, en el momento actual, el mejor algoritmo para el control de los síntomas motores durante un periodo lo más duradero posible (AU)

Different families of dopaminergic agents have allowed to increase the availability of dopamine within the central nervous system by different mechanisms of action. Each drug family has specific efficacious properties, as well as a different profile of adverse events. The knowledge in detail of these specificities is mandatory to avoid severe systemic or neuropsychiatric complications. Despite these limitations, the development of new drugs within the past 20 years has prolonged survival in Parkinson’s disease, increasing the time with preserved daily day functionality compared with the levodopa era, when this drug was the only dopaminergic drug available. The correct combination of dopaminergic drugs with different mechanisms of action allows the management of Parkinson’s disease motor symptoms within safety dose ranges, and up to day, this appears as the best algorithm to maintain functionality for longer periods of time (AU)

Paciente candidato a tratamiento con apomorfina en infusión continua / Candidate patient for treatment with continuous apomorphine infusion

La apomorfina en infusión subcutánea ha demostrado ser eficaz para reducir las fluctuaciones motoras y, en menor grado, las discinesias inducidas por levodopa en pacientes con enfermedad de Parkinson (EP) avanzada. Basándose en los datos existentes en la bibliografía, en el siguiente artículo se revisan las características clínicas que deben presentar los pacientes con EP para ser candidatos a esta terapia. En general, una gran mayoría de los pacientes con EP avanzada puede beneficiarse de esta terapia, y la experiencia de los autores indica que debería considerarse tan pronto como la terapia farmacológica convencional no logre reducir de forma significativa el número diario de horas off (AU)

Subcutaneous apomorphine infusion has been shown to be effective in reducing motor fluctuations and, to a lesser extent, also the levodopa induced dyskinesias in patients with advanced Parkinson’s disease (PD). Based on the literature data, the following article reviews the clinical features of PD patients in order to be considered candidates for this therapy. In general, the vast majority of patients with advanced PD can benefit from this therapy and the authors’ experience suggests that it should be considered as soon as the conventional pharmacological therapy fails to significantly reduce the number of daily off hours (au)

Análisis descriptivo de la actividad de una unidad de trastornos del movimiento en un hospital terciario de Cataluña / Descriptive analysis of the activity in a movement disorder unit in a tertiary hospital in Catalonia

Introducción. Los trastornos del movimiento constituyen una parte importante de la actividad de un servicio de neurología, pero hay pocos estudios que examinen su demanda asistencial. Objetivos. Analizar las primeras visitas de la Unidad de Trastornos del Movimiento del Hospital de la Santa Creu i Sant Pau de Barcelona y comparar los resultados con los de estudios previos. Pacientes y métodos. Estudio prospectivo de las primeras valoraciones realizadas durante el año 2010. Se recogieron las variables demográficas y se hizo una revisión diagnóstica a los 12 meses. Resultados. Se realizaron 423 primeras visitas (índice de solicitudes 1,41/1.000 habitantes-año): el 54,4% eran mujeres y la edad media era de 68,8 ± 14,2 años. El 74,3% de las derivaciones procedía del médico de familia. Los motivos deconsulta más frecuentes fueron temblor (40%) y parkinsonismo-torpeza motora (26%). Los diagnósticos más prevalentesfueron enfermedad de Parkinson (36%) y temblor esencial (19%). Tras la primera valoración, el 84% de los pacientes siguió controles en la unidad. Al año, en el 8% de los casos hubo un cambio en la orientación diagnóstica. El número de pacientes atendidos fue menor al estimado según la incidencia de las patologías en nuestra población (19,5 veces inferior),especialmente en los casos de síndrome de piernas inquietas, temblor esencial y síndrome de Tourette. Conclusiones. En nuestra unidad, el motivo de consulta más frecuente es el temblor, y el diagnóstico más prevalente, laenfermedad de Parkinson. El número de pacientes atendidos es claramente inferior al estimado según la incidencia de laspatologías en la población (AU)

Introduction. Movement disorders are an important part of the activity of a Neurology service, but there are few studies examining their health care demand. Aims. To analyze the first visits of the Movement Disorders Unit of the Hospital de la Santa Creu i Sant Pau in Barcelona and to compare the results with those of previous studies. Patients and methods. Prospective study of the first neurological assessments carried out during 2010. Demographicvariables of patients were collected and diagnoses were reviewed 12 months later. Results. 423 first visits were done (application rate of 1.41 per 1000 inhabitants-year): 54% females, median age 68.8 ±14.2 years-old. 74.3% of referrals came from the family doctor. The most frequent reasons for consultation were tremor (40%) and parkinsonism-motor clumsiness (26%). The most prevalent diagnoses were Parkinson’s disease (36%) and essential tremor (19%). After the first assessment, 84% of patients continued controls in the Unit. One year later, in the8% of cases there was a change in the initial diagnosis. Taking into account the incidence of each disorder, the number of patients seen was fewer compared to the estimated (19,5 times lower), especially marked in cases of restless legs syndrome, essential tremor and Tourette syndrome. Conclusions. In our Unit the most frequent reason for consultation is tremor and the most prevalent diagnosis is Parkinson’s disease. The number of patients treated is clearly lower than the estimated according to the incidence of the diseases in the population (AU)

Temblor postural: estudio clínico y neurofisiológico en una serie consecutiva de 300 paciente / Postural tremor: clinical and neurophysiological study in a consecutive series of 300 patients

FUNDAMENTO: Existen pocos estudios que analicen las características clínicas y neurofisiológicas del temblor postural en España. PACIENTES Y MÉTODO: Se realiza un estudio clínico y neurofisiológico (acelerometría y electromiografía (EMG) de músculos antagonistas) prospectivo de 300 pacientes consecutivos que consultaron por primera vez en una sección de trastornos del movimiento por temblor postural de las extremidades superiores. El diagnóstico sindrómico se estableció mediante una valoración clínica y unos criterios de apoyo neurofisiológicos. En el grupo de pacientes diagnosticados de temblor esencial (TE) se efectuaron estudios de sensibilidad diagnóstica, estudios de correlación con las variables clínicas y neurofisiológicas, así como un análisis multivariante. RESULTADOS: Los diagnósticos sindrómicos más frecuentes fueron TE (77 por ciento), temblor postural parkinsoniano (10 por ciento) y temblor fisiológico exagerado (6 por ciento). En los pacientes con TE, un 50 por ciento referían antecedentes familiares y un 7 por ciento una mejoría con el alcohol. Las variables más específicas para el diagnóstico de TE fueron: antecedentes familiares (77 por ciento), temblor cefálico (80 por ciento), mejora con alcohol (100 por ciento), patrón EMG síncrono (79 por ciento). La presencia de antecedentes familiares y el patrón EMG síncrono resultaron las únicas variables significativas predictoras de TE. Se encontró una correlación significativa entre la edad de consulta y la frecuencia (rs = -0,561; p < 0,0005) y amplitud (rs = 0,470; p < 0,0005) del temblor. CONCLUSIONES: En este estudio, el TE fue la causa más frecuente de referencia de temblor postural. Una valoración clínica dirigida junto con un estudio neurofisiológico son de gran ayuda para el diagnóstico de un paciente con temblor postural (AU)