Concomitant treatment with safinamide and antidepressant drugs: Safety data from real clinical practice / Tratamiento concomitante de safinamida y antidepresivos: Datos de seguridad sobre la práctica en la vida real

Background and purpose: The aim of this study was to assess the possible pharmacological interactions between safinamide and antidepressants, and in particular the appearance of serotonin syndrome with data from real life. Methods: We conducted a retrospective observational study of patients with Parkinson's disease from our Movement Disorders Unit, who were under treatment with any antidepressant drug and safinamide. Specifically, symptoms suggestive of serotonin syndrome were screened for. Also, we collected time of simultaneous use, doses of levodopa and other antiparkinsonian drugs. Results: Clinical records were reviewed for the study period of September 2018 to September 2019. Seventy-eight PD patients who were treated with safinamide of which 25 (32.05%) had a concomitant treatment with an antidepressant drug, being sertraline and escitalopram the most frequent. Mean age was 80 years ± 8.43 and H&Y stage was 3 [2–4]. Mean dose of levodopa used was 703.75 mg ± 233.15. Median duration of concomitant treatment with safinamide and antidepressant drug was 6 months (IQR 20.5), and over eighteen months in 5 cases. No case of serotonin syndrome was recorded, neither was any of its typical manifestations combined or in isolation. Conclusions: Our real clinical practice study suggests that concomitant use of safinamide with antidepressant drugs in PD patients seemed to be safe and well tolerated, even in the long term. However, caution is warranted, individualizing treatment regimens and monitoring the potential appearance of adverse effects.(AU)

Objetivos: El objetivo de este estudio ha sido evaluar las posibles interacciones farmacológicas entre safinamida y antidepresivos; en particular la aparición del síndrome serotoninérgico mediante datos obtenidos en la vida real. Material y métodos: Realizamos un estudio observacional retrospectivo de pacientes con enfermedad de Parkinson (EP) de nuestra unidad de trastornos del movimiento, que estaban en tratamiento con algún fármaco antidepresivo y safinamida. Específicamente, se examinaron los síntomas sugestivos de síndrome serotoninérgico. Además, se recogieron tiempos de uso simultáneo, dosis de levodopa y otros fármacos antiparkinsonianos concomitantes. Resultados: Se revisaron las historias clínicas correspondientes al período de estudio de septiembre de 2018 a septiembre de 2019. Setenta y ocho pacientes con EP se encontraban en tratamiento con safinamida, de los cuales 25 (32,05%) se encontraban recibiendo además un fármaco antidepresivo, siendo sertralina y escitalopram los más frecuentes. La edad media fue de 80 años ± 8,43 y el estadio H&Y fue de 3 [2-4]. La dosis media de levodopa utilizada fue de 703,75 mg ± 233,15. La mediana de duración del tratamiento concomitante con safinamida y un fármaco antidepresivo fue de 6 meses (IQR: 20,5), y más de 18 meses en 5 casos. No se registró ningún caso de síndrome serotoninérgico, ni tampoco ninguno de sus síntomas de forma aislada. Conclusión: Nuestro estudio de práctica clínica real sugiere que el uso concomitante de safinamida con fármacos antidepresivos en pacientes con EP parece ser seguro y bien tolerado, incluso a largo plazo. Sin embargo, es necesaria precaución, individualizando los regímenes de tratamiento, y controlando la posible aparición de efectos adversos.(AU)

Concomitant treatment with safinamide and antidepressant drugs: Safety data from real clinical practice.

BACKGROUND AND PURPOSE: The aim of this study was to assess the possible pharmacological interactions between safinamide and antidepressants, and in particular the appearance of serotonin syndrome with data from real life. METHODS: We conducted a retrospective observational study of patients with Parkinson's disease from our Movement Disorders Unit, who were under treatment with any antidepressant drug and safinamide. Specifically, symptoms suggestive of serotonin syndrome were screened for. Also, we collected time of simultaneous use, doses of levodopa and other antiparkinsonian drugs. RESULTS: Clinical records were reviewed for the study period of September 2018 to September 2019. Seventy-eight PD patients who were treated with safinamide of which 25 (32.05%) had a concomitant treatment with an antidepressant drug, being sertraline and escitalopram the most frequent. Mean age was 80 years±8.43 and H&Y stage was 3 [2-4]. Mean dose of levodopa used was 703.75mg±233.15. Median duration of concomitant treatment with safinamide and antidepressant drug was 6 months (IQR 20.5), and over eighteen months in 5 cases. No case of serotonin syndrome was recorded, neither was any of its typical manifestations combined or in isolation. CONCLUSIONS: Our real clinical practice study suggests that concomitant use of safinamide with antidepressant drugs in PD patients seemed to be safe and well tolerated, even in the long term. However, caution is warranted, individualizing treatment regimens and monitoring the potential appearance of adverse effects.

[What do medical students think about functional neurological disorders?] / ¿Qué piensan los estudiantes de Medicina sobre los trastornos neurológicos funcionales?

INTRODUCTION: Functional neurological disorders (FND) are a frequent reason for visits in neurology. However, specific training on these disorders during undergraduate and residency training is limited. This study assesses the knowledge, attitude and exposure of medical students to FNDs before completing their medical degree. PATIENTS AND METHODS: We conducted a 15-item survey to explore understanding, exposure and attitudes towards FNDs among sixth-year medical students at four Spanish universities. RESULTS: A total of 118 students (mean age 23.6 ± 1.2 years; 71.2% female) returned the survey. Of these, 88 (74.6%) were aware of the concept of FNDs and 78 (66.1%) had studied them in psychiatry classes. The term 'psychosomatic' was chosen by 54.1% of the students as the most appropriate term to refer to these disorders, and 111 (94.1%) believed that a history of sexual or physical abuse was common among FND patients. Fifty-seven students (48.3%) assumed that the diagnosis of FND was mostly a clinical diagnosis of exclusion and 63 (53.4%) indicated that it is managed only by psychiatry. One hundred and one students (85.6%) considered that adequate training on FNDs is an important aspect of their medical training. CONCLUSIONS: Medical students are aware of the existence of FNDs, but their preferred terminology, as well as the perceived aetiological factors, reflect that the historical view of these disorders is still deeply rooted. Medical students feel that they should receive adequate education on FNDs from specialists in neurology and psychiatry as part of their training.

TITLE: ¿Qué piensan los estudiantes de Medicina sobre los trastornos neurológicos funcionales?Introducción. Los trastornos neurológicos funcionales (TNF) son un motivo de consulta frecuente en neurología. Sin embargo, la formación específica sobre estos trastornos durante la formación universitaria y el período de residencia es limitada. En este estudio se evalúan los conocimientos, la actitud y la exposición de los estudiantes de Medicina a los TNF antes de terminar el grado de Medicina. Sujetos y métodos. Realizamos una encuesta de 15 ítems para explorar la comprensión, la exposición y las actitudes hacia los TNF entre los estudiantes de Medicina de sexto año en cuatro universidades españolas. Resultados. Devolvieron la encuesta 118 estudiantes (edad media 23,6 ± 1,2 años; 71,2%, mujeres). De ellos, 88 (74,6%) conocían el concepto de TNF y 78 (66,1%) los habían estudiado en las clases de psiquiatría. El 54,1% de los estudiantes eligió el término 'psicosomático' como el más adecuado para referirse a estos trastornos, y 111 (94,1%) creían que una historia de abuso sexual o físico era común entre los pacientes con TNF. Cincuenta y siete estudiantes (48,3%) asumieron que el diagnóstico de TNF era mayoritariamente un diagnóstico clínico de exclusión y 63 (53,4%) señalaron que el manejo se realiza únicamente desde psiquiatría. Ciento un estudiantes (85,6%) consideraron que una formación adecuada sobre los TNF es un aspecto importante de su formación médica. Conclusiones. Los estudiantes de Medicina son conscientes de la existencia de los TNF, pero la terminología preferida por ellos, así como los factores etiológicos percibidos, reflejan que la visión histórica acerca de estos trastornos está aún arraigada. Los estudiantes de Medicina consideran que deberían recibir una educación adecuada sobre los TNF como parte de su formación por parte de los especialistas en neurología y psiquiatría.

Radiocirugía estereotáctica con Gamma Knife como tratamiento del temblor esencial y parkinsoniano: experiencia a largo plazo / Gamma Knife stereotactic radiosurgery as a treatment for essential and parkinsonian tremor: long-term experience

Introducción: La radiocirugía estereotáctica con Gamma Knife® (GK), sobre el núcleo ventral intermedio-medial del tálamo (VIM), unilateral es una opción neuroquirúrgica mínimamente invasiva para el temblor refractario. Se describe la experiencia de talamotomía con GK (TGK) en pacientes con temblor esencial (TE) y enfermedad de Parkinson (EP) de predominio tremórico de una unidad especializada en cirugía estereotáctica.MétodosSe revisan los pacientes tratados con TGK desde enero de 2014 hasta febrero de 2018. Se analizan variables clínico-demográficas, indicación, dosis empleada, eficacia (mediante subescalas de Fahn-Tolosa-Marin (FTM) y MDS-UPDRS motora) y efectos adversos (EA).ResultadosSe registraron 13 pacientes, seis con diagnóstico de EP de predominio tremórico, cuetro con TE refractario y tres casos de TE + EP. La mediana de edad fue 78 años (62-83), con siete pacientes > 75 años. Cuatro pacientes anticoagulados y dos con antecedentes de ictus previo. La dosis máxima de radiación aplicada fue 130 Gy. La media de seguimiento fue 30,0 (14,5) meses. Se observó una mejoría significativa del temblor en las subescalas de FTM del 63,6% a 12 meses y del 63,5% al final del seguimiento y en items de temblor de MDS-UPDRS del 71,3% a 12 meses y del 60,3% al final del seguimiento. Once pacientes refirieron mejoría significativa en su calidad de vida. Tres pacientes refirieron EA leves y transitorios.ConclusionesSe presenta la mayor serie de pacientes con TE y parkinsoniano tratados con TGK en España con seguimiento a largo plazo. La TGK puede ser un tratamiento seguro y con eficacia mantenida en temblor refractario, incluso en edad avanzada o en tratamiento anticoagulante. (AU)

Introduction: Unilateral Gamma Knife™ stereotactic radiosurgery on the ventral-intermediate nucleus of the thalamus is a minimally invasive neurosurgical option for refractory tremor. We describe the experience of Gamma Knife™ thalamotomy (GKT) in patients with essential tremor (ET) and tremor-dominant Parkinson's disease (PD) at our specialised stereotactic neurosurgery unit.MethodsWe reviewed the cases of patients treated with GKT between January 2014 and February 2018 with a minimum of 12 months’ follow-up. We analysed clinical and demographic variables, indication, radiation dose, effectiveness (based on subscales of the Fahn-Tolosa-Marin [FTM] scale and the Movement Disorders Society-Unified Parkinson's Disease Rating Scale [MDS-UPDRS] motor score), and adverse events.ResultsThirteen patients were registered, 6 with a diagnosis of tremor-dominant PD, four with refractory ET, and three with ET and PD. Median age was 78 years (range, 62-83), with seven patients aged over 75 years. Four patients were receiving anticoagulants and two had history of stroke. The maximum radiation dose administered was 130 Gy. Mean (standard deviation) follow-up duration was 30.0 (14.5) months. Significant tremor improvement was observed on the FTM subscales: 63.6% at 12 months and 63.5% at the end of follow-up; MDS-UPDRS tremor items showed improvements of 71.3% at 12 months and 60.3% at the end of follow up. Eleven patients reported significant improvements in quality of life, and 3 reported mild and transient adverse effects.ConclusionsThis is the largest series of patients with essential and parkinsonian tremor treated with GKT and followed up in the long term in Spain. GKT can be safe and effective in the long term in patients with refractory tremor, including in elderly patients and those receiving anticoagulants. (AU)

Gamma Knife® stereotactic radiosurgery as a treatment for essential and parkinsonian tremor: long-term experience.

INTRODUCTION: Unilateral Gamma Knife™ stereotactic radiosurgery on the ventral-intermediate nucleus of the thalamus is a minimally invasive neurosurgical option for refractory tremor. We describe the experience of Gamma Knife™ thalamotomy (GKT) in patients with essential tremor (ET) and tremor-dominant Parkinson's disease (PD) at our specialised stereotactic neurosurgery unit. METHODS: We reviewed the cases of patients treated with GKT between January 2014 and February 2018 with a minimum of 12 months' follow-up. We analysed clinical and demographic variables, indication, radiation dose, effectiveness (based on subscales of the Fahn-Tolosa-Marin [FTM] scale and the Movement Disorders Society-Unified Parkinson's Disease Rating Scale [MDS-UPDRS] motor score), and adverse events. RESULTS: Thirteen patients were registered, 6 with a diagnosis of tremor-dominant PD, four with refractory ET, and three with ET and PD. Median age was 78 years (range, 62-83), with seven patients aged over 75 years. Four patients were receiving anticoagulants and two had history of stroke. The maximum radiation dose administered was 130 Gy. Mean (standard deviation) follow-up duration was 30.0 (14.5) months. Significant tremor improvement was observed on the FTM subscales: 63.6% at 12 months and 63.5% at the end of follow-up; MDS-UPDRS tremor items showed improvements of 71.3% at 12 months and 60.3% at the end of follow up. Eleven patients reported significant improvements in quality of life, and 3 reported mild and transient adverse effects. CONCLUSIONS: This is the largest series of patients with essential and parkinsonian tremor treated with GKT and followed up in the long term in Spain. GKT can be safe and effective in the long term in patients with refractory tremor, including in elderly patients and those receiving anticoagulants.

Concomitant treatment with safinamide and antidepressant drugs: Safety data from real clinical practice.

BACKGROUND AND PURPOSE: The aim of this study was to assess the possible pharmacological interactions between safinamide and antidepressants, and in particular the appearance of serotonin syndrome with data from real life. METHODS: We conducted a retrospective observational study of patients with Parkinson's disease from our Movement Disorders Unit, who were under treatment with any antidepressant drug and safinamide. Specifically, symptoms suggestive of serotonin syndrome were screened for. Also, we collected time of simultaneous use, doses of levodopa and other antiparkinsonian drugs. RESULTS: Clinical records were reviewed for the study period of September 2018 to September 2019. Seventy-eight PD patients who were treated with safinamide of which 25 (32.05%) had a concomitant treatment with an antidepressant drug, being sertraline and escitalopram the most frequent. Mean age was 80 years±8.43 and H&Y stage was 3 [2-4]. Mean dose of levodopa used was 703.75mg±233.15. Median duration of concomitant treatment with safinamide and antidepressant drug was 6 months (IQR 20.5), and over eighteen months in 5 cases. No case of serotonin syndrome was recorded, neither was any of its typical manifestations combined or in isolation. CONCLUSIONS: Our real clinical practice study suggests that concomitant use of safinamide with antidepressant drugs in PD patients seemed to be safe and well tolerated, even in the long term. However, caution is warranted, individualizing treatment regimens and monitoring the potential appearance of adverse effects.

Manejo de la enfermedad de Parkinson y otros trastornos del movimiento en mujeres en edad fértil: Parte 1 / Management of Parkinson's disease and other movement disorders in woman of childbearing age: Part 1

INTRODUCCIÓN: El manejo de la enfermedad de Parkinson en la mujer en edad fértil nos plantea como principal reto el manejo de la enfermedad y los fármacos durante el embarazo y lactancia. El aumento de la edad gestacional de la mujer hace más probable que la incidencia de embarazos pueda incrementarse. OBJETIVO: Definir las características clínicas y los factores que condicionan la vida de la mujer en edad fértil con enfermedad de Parkinson y definir una guía de actuación y manejo del embarazo en estas pacientes. RESULTADOS: Este documento de consenso se ha realizado mediante una búsqueda bibliográfica exhaustiva y discusión de los contenidos realizados por un grupo de expertos en trastornos del movimiento de la Sociedad Española de Neurología. CONCLUSIONES: La enfermedad de Parkinson afecta a todos los aspectos relacionados con la salud sexual y reproductiva de la mujer en edad fértil. Se debe planificar el embarazo en las mujeres con enfermedad de Parkinson para minimizar los riesgos teratogénicos sobre el feto. Se recomienda un abordaje multidisciplinar de estas pacientes para tener en cuenta todos los aspectos implicados

INTRODUCTION: The main challenge of Parkinson's disease in women of childbearing age is managing symptoms and drugs during pregnancy and breastfeeding. The increase in the age at which women are having children makes it likely that these pregnancies will become more common in future. OBJECTIVES: This study aims to define the clinical characteristics of women of childbearing age with Parkinson's disease and the factors affecting their lives, and to establish a series of guidelines for managing pregnancy in these patients. RESULTS: This consensus document was developed through an exhaustive literature search and a discussion of the available evidence by a group of movement disorder experts from the Spanish Society of Neurology. CONCLUSIONS: Parkinson's disease affects all aspects of sexual and reproductive health in women of childbearing age. Pregnancy should be well planned to minimise teratogenic risk. A multidisciplinary approach should be adopted in the management of these patients in order to take all relevant considerations into account

Manejo de la enfermedad de Parkinson y otros trastornos del movimiento en mujeres en edad fértil: parte 2 / Management of Parkinson's disease and other movement disorders in women of childbearing age: Part 2

INTRODUCCIÓN: Muchas enfermedades que cursan con trastornos del movimiento hipercinético comienzan o afectan a mujeres en edad fértil. Es importante conocer los riesgos que tienen las mujeres con estas enfermedades durante el embarazo, así como los posibles efectos de los tratamientos sobre el feto. OBJETIVOS: Definir las características clínicas y los factores que condicionan la vida de la mujer en edad fértil con distonía, corea, síndrome de Tourette, temblor y síndrome de piernas inquietas. Definir una guía de actuación y manejo del embarazo y lactancia en las pacientes con esta enfermedad. DESARROLLO: Este documento de consenso se ha realizado mediante una búsqueda bibliográfica exhaustiva y discusión de los contenidos llevadas a cabo por un Grupo de Expertos en Trastornos del Movimiento de la Sociedad Española de Neurología (SEN). CONCLUSIONES: En todas las mujeres que padecen o comienzan con trastornos del movimiento hipercinéticos se debe valorar el riesgo-beneficio de los tratamientos, reducir al máximo la dosis eficaz o administrarlo de forma puntual en los casos en que sea posible. En aquellas enfermedades de causa hereditaria es importante un consejo genético para las familias. Es importante reconocer los trastornos del movimiento desencadenados durante el embarazo como determinadas coreas y síndrome de piernas inquietas

INTRODUCTION: Many diseases associated with hyperkinetic movement disorders manifest in women of childbearing age. It is important to understand the risks of these diseases during pregnancy, and the potential risks of treatment for the fetus. OBJECTIVES: This study aims to define the clinical characteristics and the factors affecting the lives of women of childbearing age with dystonia, chorea, Tourette syndrome, tremor, and restless legs syndrome, and to establish guidelines for management of pregnancy and breastfeeding in these patients. RESULTS: This consensus document was developed through an exhaustive literature search and a discussion of the content by a group of movement disorder experts from the Spanish Society of Neurology. CONCLUSIONS: We must evaluate the risks and benefits of treatment in all women with hyperkinetic movement disorders, whether pre-existing or with onset during pregnancy, and aim to reduce effective doses as much as possible or to administer drugs only when necessary. In hereditary diseases, families should be offered genetic counselling. It is important to recognise movement disorders triggered during pregnancy, such as certain types of chorea and restless legs syndrome

Management of Parkinson's disease and other movement disorders in woman of childbearing age: Part 1. / Manejo de la enfermedad de Parkinson y otros trastornos del movimiento en mujeres en edad fértil: Parte 1.

INTRODUCTION: The main challenge of Parkinson's disease in women of childbearing age is managing symptoms and drugs during pregnancy and breastfeeding. The increase in the age at which women are having children makes it likely that these pregnancies will become more common in future. OBJECTIVES: This study aims to define the clinical characteristics of women of childbearing age with Parkinson's disease and the factors affecting their lives, and to establish a series of guidelines for managing pregnancy in these patients. RESULTS: This consensus document was developed through an exhaustive literature search and a discussion of the available evidence by a group of movement disorder experts from the Spanish Society of Neurology. CONCLUSIONS: Parkinson's disease affects all aspects of sexual and reproductive health in women of childbearing age. Pregnancy should be well planned to minimise teratogenic risk. A multidisciplinary approach should be adopted in the management of these patients in order to take all relevant considerations into account.

Management of Parkinson's disease and other movement disorders in women of childbearing age: Part 2. / Manejo de la enfermedad de Parkinson y otros trastornos del movimiento en mujeres en edad fértil: parte 2.

INTRODUCTION: Many diseases associated with hyperkinetic movement disorders manifest in women of childbearing age. It is important to understand the risks of these diseases during pregnancy, and the potential risks of treatment for the fetus. OBJECTIVES: This study aims to define the clinical characteristics and the factors affecting the lives of women of childbearing age with dystonia, chorea, Tourette syndrome, tremor, and restless legs syndrome, and to establish guidelines for management of pregnancy and breastfeeding in these patients. RESULTS: This consensus document was developed through an exhaustive literature search and a discussion of the content by a group of movement disorder experts from the Spanish Society of Neurology. CONCLUSIONS: We must evaluate the risks and benefits of treatment in all women with hyperkinetic movement disorders, whether pre-existing or with onset during pregnancy, and aim to reduce effective doses as much as possible or to administer drugs only when necessary. In hereditary diseases, families should be offered genetic counselling. It is important to recognise movement disorders triggered during pregnancy, such as certain types of chorea and restless legs syndrome.

COVID-19 in Parkinson's disease: what holds the key?

INTRODUCTION: Parkinson's disease (PD) is more frequent in the elderly and increases the risk of respiratory infections. Previous data on PD and SARS-CoV-2 are scarce, suggesting a poor prognosis in advanced disease and second-line therapies. METHODS: A retrospective case-control study comparing patients with PD and COVID-19 and patients with PD without COVID-19 was conducted during the pandemic period in Spain (March 1st-July 31st 2020) in a tertiary university hospital. RESULTS: Thirty-nine (COVID-19 +) and 172 (COVID-19-) PD patients were included. Fifty-nine percent were males in both groups, with similar age (75.9 ± 9.0 COVID-19 + , 73.9 ± 10.0 COVID-19-), disease duration (8.9 ± 6.2 COVID-19 + , 8.5 ± 5.6 COVID-19-) and PD treatments. COVID-19 was mild in 10 (26%), required admission in 21 (54%) and caused death in 8 (21%) patients. Dementia was the only comorbidity more frequent in COVID-19 + patients (36% vs. 14%, p = 0.0013). However, in a multivariate analysis, institutionalization was the only variable associated with COVID-19 + (OR 17.0, 95% CI 5.0-60.0, p < 0.001). When considering severe COVID-19 (admission or death) vs. mild or absent COVID-19, institutionalization, neoplasm, dementia and a lower frequency of dopamine agonists were associated with severe COVID-19. In multivariate analysis, only institutionalization [OR 5.17, 95% CI 1.57-17, p = 0.004] and neoplasm [OR 8.0, 95%CI 1.27-49.8, p = 0.027] remained significantly associated. CONCLUSION: In our experience, institutionalization and oncologic comorbidity, rather than PD-related variables, increased the risk of developing COVID-19, and impacted on its severity. These findings suggest that epidemiologic factors and frailty are key factors for COVID-19 morbidity/mortality in PD. Appropriate preventive strategies should be implemented in institutionalized patients to prevent infection and improve prognosis.

Gamma Knife® stereotactic radiosurgery as a treatment for essential and parkinsonian tremor: long-term experience. / Radiocirugía estereotáctica con Gamma Knife® como tratamiento del temblor esencial y parkinsoniano: experiencia a largo plazo.

INTRODUCTION: Unilateral Gamma Knife™ stereotactic radiosurgery on the ventral-intermediate nucleus of the thalamus is a minimally invasive neurosurgical option for refractory tremor. We describe the experience of Gamma Knife™ thalamotomy (GKT) in patients with essential tremor (ET) and tremor-dominant Parkinson's disease (PD) at our specialised stereotactic neurosurgery unit. METHODS: We reviewed the cases of patients treated with GKT between January 2014 and February 2018 with a minimum of 12 months' follow-up. We analysed clinical and demographic variables, indication, radiation dose, effectiveness (based on subscales of the Fahn-Tolosa-Marin [FTM] scale and the Movement Disorders Society-Unified Parkinson's Disease Rating Scale [MDS-UPDRS] motor score), and adverse events. RESULTS: Thirteen patients were registered, 6 with a diagnosis of tremor-dominant PD, four with refractory ET, and three with ET and PD. Median age was 78 years (range, 62-83), with seven patients aged over 75 years. Four patients were receiving anticoagulants and two had history of stroke. The maximum radiation dose administered was 130 Gy. Mean (standard deviation) follow-up duration was 30.0 (14.5) months. Significant tremor improvement was observed on the FTM subscales: 63.6% at 12 months and 63.5% at the end of follow-up; MDS-UPDRS tremor items showed improvements of 71.3% at 12 months and 60.3% at the end of follow up. Eleven patients reported significant improvements in quality of life, and 3 reported mild and transient adverse effects. CONCLUSIONS: This is the largest series of patients with essential and parkinsonian tremor treated with GKT and followed up in the long term in Spain. GKT can be safe and effective in the long term in patients with refractory tremor, including in elderly patients and those receiving anticoagulants.

Contingent negative variation: a biomarker of abnormal attention in functional movement disorders.

BACKGROUND AND PURPOSE: Contingent negative variation (CNV) is a negative cortical wave that precedes a pre-cued imperative stimulus requiring a quick motor response. It has been related to motor preparation and anticipatory attention. The aim was to ascertain whether the clinical improvement of functional movement disorders after physiotherapy would be associated with faster reaction times and modulation of CNV. METHODS: Motor performance and CNV were analysed during a pre-cued choice reaction time task with varying cue validity. Twenty-one patients with functional movement disorders and 13 healthy controls at baseline were compared. Patients then underwent physiotherapy. At follow-up after physiotherapy, patients were categorized as clinically improved (responders) or not improved (non-responders) and retested. RESULTS: At baseline, patients did not generate CNV, contrary to controls [mean amplitude (µV) at the end of preparation to move: patients -0.47 (95% CI -1.94, 1.00) versus controls -2.59 (95% CI -4.46, -0.72)]. Responders performed faster after physiotherapy [mean natural logarithm (ln) reaction time (RT) (ms): follow-up 6.112 (95% CI 5.923, 6.301) versus baseline 6.206 (95% CI 6.019, 6.394), P = 0.010], contrary to non-responders. Simultaneously, responders showed a recovery of CNV after physiotherapy [follow-up -1.95 (95% CI -3.49, -0.41) versus baseline -0.19 (95% CI -1.73, 1.35), P < 0.001], contrary to non-responders [follow-up -0.32 (95% CI -1.79, 1.14) versus baseline -0.72 (95% CI -2.19, 0.75), P = 0.381]. CONCLUSIONS: Clinical improvement of functional movement disorders after physiotherapy was associated with faster reaction times and normalization of CNV, which was absent at baseline. These findings suggest that CNV may constitute a useful neurophysiological biomarker related to abnormal attention in functional movement disorders.

Abnormal movement-related suppression of sensory evoked potentials in upper limb dystonia.

BACKGROUND: Gating of sensory evoked potentials (SEPs) around the onset of a voluntary movement is a physiological phenomenon with centripetal and central components, and may reflect sensorimotor integration required for normal movement control. OBJECTIVE: Our objective was the investigation of SEP suppression at the onset of movement and the interaction between SEP suppression and vibration of the limb. METHODS: Fourteen patients with primary focal/segmental dystonia and 17 age-matched healthy volunteers were studied. SEPs were elicited after electrical stimulation of the median nerve at the wrist. Electroencephalograms (EEGs) were recorded over the scalp at three sites according to the International 10-20 System (F3, C3 and P3). SEPs were recorded in four conditions: at rest, at the onset of movement (a self-paced abduction movement of the right thumb), both in the absence and in the presence of vibration of the limb. RESULTS: Repeated measures anova revealed that there was a significant main effect of group [F(1, 11.1) = 0.471, P = 0.002]. Post hoc exploration of this effect revealed it to be due to an absence of SEP suppression at movement onset in patients (mean ratio SEP movement onset/rest 1.15 at F3, 1.13 at C3, 1.01 at P3) compared to controls, who had SEP suppression at movement onset (mean ratio SEP movement onset/rest 0.79 at F3, 0.78 at C3, 0.77 at P3). With vibration, SEP suppression reduced in both patients and controls to a similar extent. CONCLUSION: These results demonstrate abnormal SEP suppression at the onset of movement in patients with primary dystonia, and in addition that vibration of the limb reduces SEP suppression in patients and controls.

Symptom severity in patients with functional motor symptoms: Patient's perception and doctor's clinical assessment.

BACKGROUND: Beliefs and expectations about symptoms and an abnormal direction of attention towards the body have been proposed as important mechanistic factors in the pathophysiology of functional motor symptoms (FMS). We therefore aimed to evaluate patients' awareness/perception of the presence and severity of their own symptoms before and while watching themselves in a video and to compare this with doctors' assessment of the presence and severity of FMS, based on video evaluation. METHODS: We evaluated 16 patients affected by FMS. Patients were invited to give a "subjective evaluation" of their symptoms. Afterwards, patients were invited to watch a video of themselves and to judge the presence of symptoms in the different body parts and, if so, to rate the severity. Patients' videos were also assessed by a rater with expertise in FMS. RESULTS: Patients judged their symptoms to be more severe on subjective evaluation than when viewing a video of themselves (p = 0.002; t = 3.656). Subjective evaluation of symptom severity by patients was higher than that of raters viewing a video of the patient (p < 0.001, t = 4.860), but there was only a trend towards a difference between video ratings of severity by patients and independent raters (p = 0.017, t = 2.962 with p set at 0.016 according to Bonferroni correction). CONCLUSIONS: Our study shows that patients with FMS tend to overestimate the severity of their symptoms compared independent rating. However, when viewing a video of themselves they rated their symptoms as less severe and closer to those of independent raters.

All in the blink of an eye: new insight into cerebellar and brainstem function in DYT1 and DYT6 dystonia.

BACKGROUND AND PURPOSE: Traditionally dystonia has been considered a disorder of basal ganglia dysfunction. However, recent research has advocated a more complex neuroanatomical network. In particular, there is increasing interest in the pathophysiological role of the cerebellum. Patients with cervical and focal hand dystonia have impaired cerebellar associative learning using the paradigm eyeblink conditioning. This is perhaps the most direct evidence to date that the cerebellum is implicated in patients. METHODS: Eleven patients with DYT1 dystonia and five patients with DYT6 dystonia were examined and rates of eyeblink conditioning were compared with age-matched controls. A marker of brainstem excitability, the blink reflex recovery, was also studied in the same groups. RESULTS: Patients with DYT1 and DYT6 dystonia have a normal ability to acquire conditioned responses. Blink reflex recovery was enhanced in DYT1 but this effect was not seen in DYT6. CONCLUSIONS: If the cerebellum is an important driver in DYT1 and DYT6 dystonia our data suggest that there is specific cerebellar dysfunction such that the circuits essential for conditioning function normally. Our data are contrary to observations in focal dystonia and suggest that the cerebellum may have a distinct role in different subsets of dystonia. Evidence of enhanced blink reflex recovery in all patients with dystonia was not found and recent studies calling for the blink recovery reflex to be used as a diagnostic test for dystonic tremor may require further corroboration.

A positive diagnosis of functional (psychogenic) tics.

BACKGROUND AND PURPOSE: Functional tics, also called psychogenic tics or pseudo-tics, are difficult to diagnose because of the lack of diagnostic criteria and their clinical similarities to organic tics. The aim of the present study was to report a case series of patients with documented functional tics and to describe their clinical characteristics, risk factors and psychiatric comorbidity. Also clinical tips are suggested which might help the differential diagnosis in clinical practice. METHODS AND RESULTS: Eleven patients (mean age at onset 37.2, SD 13.5; three females) were included with a documented or clinically established diagnosis of functional tics, according to consultant neurologists who have specific expertise in functional movement disorders or in tic disorders. Adult onset, absent family history of tics, inability to suppress the movements, lack of premonitory sensations, absence of pali-, echo- and copro-phenomena, presence of blocking tics, the lack of the typical rostrocaudal tic distribution and the coexistence of other functional movement disorders were common in our patients. CONCLUSIONS: Our data suggest that functional tics can be differentiated from organic tics on clinical grounds, although it is also accepted that this distinction can be difficult in certain cases. Clinical clues from history and examination described here might help to identify patients with functional tics.

Tremulous cervical dystonia is likely to be familial: clinical characteristics of a large cohort.

BACKGROUND: Primary cervical dystonia is the most common form of adult-onset focal dystonia. Although most frequently sporadic, 15-20% of patients report a positive family history, suggesting a possible genetic cause. Head tremor is often present in patients with cervical dystonia and may be a prominent symptom. OBJECTIVE: To describe the clinical characteristics of patients with tremulous cervical dystonia. METHODS: Patients with primary cervical dystonia attending our botulinum toxin clinic were assessed with an interview and neurological examination and their notes reviewed. Patients were classified as having either tremulous or non-tremulous cervical dystonia, according to the presence or absence of head tremor on examination. Clinical and demographic data were compared between groups. RESULTS: From 273 patients included (190 females, 83 males), 125 (46%) were classified as tremulous and 148 (54%) as non-tremulous. Tremulous patients were more likely to have a segmental distribution (61% vs. 25%), often involving the arms (48%), and had more frequently associated arm tremor (55% vs. 10%). A positive family history of dystonia and/or tremor was more frequent in tremulous patients (50% vs. 18%). CONCLUSIONS: Patients with cervical dystonia with associated head tremor are more likely to have a segmental distribution (with frequent arm involvement), associated arm tremor and a positive family history, suggesting a genetic etiology in this subgroup of patients.

Adaptation of surround inhibition in the human motor system.

Adaptation of a rapid ballistic movement requires that commands for the next movement are updated on the basis of sensory error signals from the current movement. Previous experiments, mostly using visual feedback, have demonstrated that adaptation is highly sensitive to the timing of feedback and can be substantially impaired by delays of 100 ms or so. Here, we use the phenomenon of surround inhibition (SI) to explore the consequences of somatosensory feedback delay in a task requiring participants to flex the index finger without generating any electromyographical (EMG) activity in other fingers. Participants were requested to perform brief isolated flexion movements of the index finger. After a short period of practice, SI in the distant abductor digiti minimi (ADM) muscle was quantified by measuring the amplitude of EMG responses evoked by a standard pulse of transcranial magnetic stimulation to the contralateral motor cortex at the onset of flexion. SI indicates that the response during flexion was smaller than the response at rest. After this, two training blocks were performed in which the ADM muscle was vibrated (80 Hz, 100 ms) either at the onset (VIB(onset)) of finger flexion or with a delay of 100 ms (VIB(100)). SI was reassessed after training. SI measured after VIB(onset) training was transiently more effective than at baseline. In contrast, SI was unchanged compared to baseline after VIB(100). The present study demonstrates that SI can be modified by experience. The timing of the sensory stimulation was found to be critical for the modification of SI, suggesting that only sensory signals closely related to the movement onset can induce adaptive changes, presumably through a feed-forward process.