[Essential tremor: are we just splitting hairs? Non-motor symptoms and essential tremor-plus]. / Temblor esencial: ¿el gato tiene cinco pies? Síntomas no motores y temblor esencial plus.

INTRODUCTION: The existence of non-motor symptoms in essential tremor (ET) and the appearance of a new condition, ET-plus, are two controversial issues. AIMS: To offer a review of the current status of these two topics. DEVELOPMENT: We performed an analysis of the studies conducted on non-motor symptoms in ET and of the articles for and against the use of the term ET-plus. CONCLUSIONS: Non-motor symptoms have gained increased recognition as a feature accompanying ET. Several studies have documented its presence compared to matched controls. It is not clear, however, whether these non-motor symptoms would be part of the spectrum of ET symptoms (a primary phenomenon) or whether they would be symptoms that appear as a consequence of the physical or psychological disability produced by the clinical signs and symptoms of ET itself (a secondary phenomenon). For the time being, their evaluation and treatment are not included within the standard assessment of patients with ET. In view of the heterogeneous phenotype, the term ET-plus aims to improve phenotypic homogeneity for genetic or therapeutic studies. Yet, there is no pathological basis, and epidemiological, genetic and therapeutic research studies have numerous drawbacks. In the absence of clear objective biomarkers, distinguishing between ET and ET-plus by clinical distinction alone is very complex. We should be cautious about using new terms that are not yet backed by sound scientific evidence.

TITLE: Temblor esencial: ¿el gato tiene cinco pies? Síntomas no motores y temblor esencial plus.Introducción. La existencia de síntomas no motores en el temblor esencial (TE) y la aparición de una nueva entidad, el TE plus, son dos temas controvertidos. Objetivos. Exponer una revisión del estado actual de estos dos temas. Desarrollo. Análisis de los estudios sobre síntomas no motores en el TE, y de los artículos favorables y contrarios al término TE plus. Conclusiones. Los síntomas no motores han aumentado su reconocimiento como un dato acompañante del TE. Varios estudios han documentado su presencia en comparación con controles pareados. Ahora bien, no está claro si estos síntomas no motores formarían parte del espectro de síntomas del TE (fenómeno primario), o si se trataría de síntomas que aparecen como consecuencia de la discapacidad física o psíquica producida por la propia sintomatología del TE (fenómeno secundario). De momento, su evaluación y su tratamiento no forman parte de la valoración estándar de los pacientes con TE. Ante el fenotipo heterogéneo, el término TE plus intenta mejorar la homogeneidad fenotípica de cara a los estudios genéticos o terapéuticos. Ahora bien, no existe una base patológica y existen numerosos inconvenientes para los estudios de investigación epidemiológicos, genéticos y terapéuticos. En ausencia de biomarcadores objetivos claros, la distinción entre TE y TE plus únicamente por distinción clínica es muy compleja. Debemos ser cautos a la hora de utilizar nuevos términos que no están todavía soportados por una base científica.

Temblor esencial: ¿el gato tiene cinco pies? Síntomas no motores y temblor esencial plus / Essential tremor: are we just splitting hairs? Non-motor symptoms and essential tremor-plus

Introducción: La existencia de síntomas no motores en el temblor esencial (TE) y la aparición de una nueva entidad, el TE plus, son dos temas controvertidos. Objetivos: Exponer una revisión del estado actual de estos dos temas. Desarrollo: Análisis de los estudios sobre síntomas no motores en el TE, y de los artículos favorables y contrarios al término TE plus. Conclusiones: Los síntomas no motores han aumentado su reconocimiento como un dato acompañante del TE. Varios estudios han documentado su presencia en comparación con controles pareados. Ahora bien, no está claro si estos síntomas no motores formarían parte del espectro de síntomas del TE (fenómeno primario), o si se trataría de síntomas que aparecen como consecuencia de la discapacidad física o psíquica producida por la propia sintomatología del TE (fenómeno secundario). De momento, su evaluación y su tratamiento no forman parte de la valoración estándar de los pacientes con TE. Ante el fenotipo heterogéneo, el término TE plus intenta mejorar la homogeneidad fenotípica de cara a los estudios genéticos o terapéuticos. Ahora bien, no existe una base patológica y existen numerosos inconvenientes para los estudios de investigación epidemiológicos, genéticos y terapéuticos. En ausencia de biomarcadores objetivos claros, la distinción entre TE y TE plus únicamente por distinción clínica es muy compleja. Debemos ser cautos a la hora de utilizar nuevos términos que no están todavía soportados por una base científica.(AU)

Introduction: The existence of non-motor symptoms in essential tremor (ET) and the appearance of a new condition, ET-plus, are two controversial issues. Aims: To offer a review of the current status of these two topics. Development: We performed an analysis of the studies conducted on non-motor symptoms in ET and of the articles for and against the use of the term ET-plus. Conclusions: Non-motor symptoms have gained increased recognition as a feature accompanying ET. Several studies have documented its presence compared to matched controls. It is not clear, however, whether these non-motor symptoms would be part of the spectrum of ET symptoms (a primary phenomenon) or whether they would be symptoms that appear as a consequence of the physical or psychological disability produced by the clinical signs and symptoms of ET itself (a secondary phenomenon). For the time being, their evaluation and treatment are not included within the standard assessment of patients with ET. In view of the heterogeneous phenotype, the term ET-plus aims to improve phenotypic homogeneity for genetic or therapeutic studies. Yet, there is no pathological basis, and epidemiological, genetic and therapeutic research studies have numerous drawbacks. In the absence of clear objective biomarkers, distinguishing between ET and ET-plus by clinical distinction alone is very complex. We should be cautious about using new terms that are not yet backed by sound scientific evidence.(AU)

Measuring impulsivity in Parkinson's disease: a correlational and structural neuroimaging study using different tests.

BACKGROUND AND PURPOSE: Impulsivity is an aspect of personality and a major component of multiple neuropsychiatric conditions. In Parkinson's disease, it has been associated with the expression of impulse control disorders, a highly prevalent non-motor complication. Even though multiple tests of impulsivity have been used in this context, the impact of test choice has not been addressed. The aim was to evaluate whether different impulsivity measures in Parkinson's disease share substantial inter-scale and anatomical correlations or rather mirror different underlying phenomena. METHODS: In a consecutive sample of 89 Parkinson's disease patients without impulse control disorders, four common tests were evaluated assessing different aspects of impulsivity: impulsiveness trait, decisions under implicit risk with and without losses, and delay discounting. Correlations among test scores were analysed and each score was used as a regressor in a set of grey matter volume (GMV) voxel-based morphometry analyses to explore their brain structural correlates. RESULTS: No significant correlations were found between the different impulsivity tests. Furthermore, their structural brain correlates were divergent. Impulsiveness trait appeared to be associated with lower GMV in dorsal-lateral prefrontal cortices, implicit risk (with losses) with higher GMV in the left nucleus accumbens and lower left insular GMV, implicit risk (without losses) with higher GMV in the left lingual gyrus and lower GMV in the gyri recti and delay discounting with higher GMV in the left nucleus accumbens. CONCLUSIONS: In Parkinson's disease, different impulsivity measures reflect very dissimilar behavioural and brain structural correlates. Our results suggest that parkinsonian impulsivity is not a unitary phenomenon but rather a heterogeneous entity.

Unidades de trastornos del movimiento y tratamiento de las fluctuaciones motoras de la enfermedad de Parkinson avanzada / Movement disorders units and management of motor fluctuations in advanced Parkinson's disease

Introducción. La enfermedad de Parkinson (EP) avanzada conlleva complicaciones, como fluctuaciones motoras. Su atención sanitaria en España se realiza frecuentemente en unidades de trastornos del movimiento (UTM). Objetivo. Conocer los recursos diagnósticos y el abordaje terapéutico de las UTM. Sujetos y métodos. Estudio descriptivo, transversal. Se diseñó un cuestionario en línea, dirigido a neurólogos de UTM, de 48 preguntas sobre recursos disponibles, número de pacientes atendidos con EP y con fluctuaciones motoras, y abordaje terapéutico según el estadio de Hoehn y Yahr (H&Y). Resultados. Participaron 55 neurólogos. Disponen de neuroimagen estructural el 100%; neuroimagen funcional, el 89%; tests agudos farmacológicos, el 89%; tests genéticos, el 78%, y ecografía transcraneal, el 53%. Hay 2,5 neurólogos y 1,2 enfermeras por unidad. Atienden a un 19% de pacientes con EP en estadio de H&Y 1, un 59% en estadio de H&Y 2-3 y un 22% en estadio de H&Y 4-5. Utilizan en primer lugar los inhibidores de la monoaminooxidasa B en los estadios de H&Y 1 y 2, y levodopa en los estadios de H&Y 3, 4 y 5. Un 24% de los pacientes tiene fluctuaciones motoras, con 5,5 episodios off diarios, de 44 minutos, con un total de siete horas off diarias. Un 14% de los pacientes de hasta 70 años con más de tres episodios off diarios de larga duración recibe tratamiento invasivo para las fluctuaciones motoras. Conclusiones. Las UTM están bien dotadas de recursos diagnósticos y farmacológicos. Los tratamientos farmacológicos se individualizan con gran variedad de combinaciones. A pesar de esta optimización, la prevalencia de fluctuaciones motoras es todavía alta en pacientes avanzados, y las terapias invasivas pueden infrautilizarse (AU)

Introduction. Advanced Parkinson's disease (PD) entails complications, such as motor fluctuations. In Spain, medical attention for such cases is often provided in movement disorder units (MDU). Aim. To gain further knowledge of the diagnostic resources and therapeutic approach of MDU. Subjects and methods. A descriptive cross-sectional study was conducted. The researchers designed an on-line questionnaire, addressed to neurologists from MDUs, containing 48 questions about the resources they have available, the number of patients with PD and motor fluctuations that have been attended to, as well as the therapeutic approach, according to the Hoehn and Yahr (H&Y) scale. Results. Fifty-five neurologists participated. Structural neuroimaging is available to 100% of them; 89% have access tofunctional neuroimaging; 89% have acute pharmacological tests available for use; 78% have access to genetic tests; and 53% have transcranial ultrasound at their disposal. There are 2.5 neurologists and 1.2 nurses per unit. Of the patients with PD that they see, 19% of them are in H&Y stage 1, 59% are in H&Y stage 2-3 and 22% are in H&Y stage 4-5. Treatment consists, first of all, in monoamine oxidase type B inhibitors in H&Y stages 1 and 2, and levodopa in H&Y stages 3, 4 and 5. Twenty-four per cent of the patients have motor fluctuations, with 5.5 off episodes per day, lasting 44 minutes, with a total of seven off hours per day. Fourteen per cent of the patients under 70 years of age with more than three long-term off episodes per day are receiving invasive treatment for motor fluctuations. Conclusions. MDUs are well equipped with diagnostic and pharmacological resources. Pharmacological treatments are tailored to each patient with a wide range of combinations. Despite this optimisation, the prevalence of motor fluctuations is still high in advanced patients, and invasive therapies may be underused (AU)

[Movement disorders units and management of motor fluctuations in advanced Parkinson's disease]. / Unidades de trastornos del movimiento y tratamiento de las fluctuaciones motoras de la enfermedad de Parkinson avanzada.

INTRODUCTION: Advanced Parkinson's disease (PD) entails complications, such as motor fluctuations. In Spain, medical attention for such cases is often provided in movement disorder units (MDU). AIM: To gain further knowledge of the diagnostic resources and therapeutic approach of MDU. SUBJECTS AND METHODS: A descriptive cross-sectional study was conducted. The researchers designed an on-line questionnaire, addressed to neurologists from MDUs, containing 48 questions about the resources they have available, the number of patients with PD and motor fluctuations that have been attended to, as well as the therapeutic approach, according to the Hoehn and Yahr (HY) scale. RESULTS: Fifty-five neurologists participated. Structural neuroimaging is available to 100% of them; 89% have access to functional neuroimaging; 89% have acute pharmacological tests available for use; 78% have access to genetic tests; and 53% have transcranial ultrasound at their disposal. There are 2.5 neurologists and 1.2 nurses per unit. Of the patients with PD that they see, 19% of them are in HY stage 1, 59% are in HY stage 2-3 and 22% are in HY stage 4-5. Treatment consists, first of all, in monoamine oxidase type B inhibitors in HY stages 1 and 2, and levodopa in HY stages 3, 4 and 5. Twenty-four per cent of the patients have motor fluctuations, with 5.5 off episodes per day, lasting 44 minutes, with a total of seven off hours per day. Fourteen per cent of the patients under 70 years of age with more than three long-term off episodes per day are receiving invasive treatment for motor fluctuations. CONCLUSIONS: MDUs are well equipped with diagnostic and pharmacological resources. Pharmacological treatments are tailored to each patient with a wide range of combinations. Despite this optimisation, the prevalence of motor fluctuations is still high in advanced patients, and invasive therapies may be underused.

TITLE: Unidades de trastornos del movimiento y tratamiento de las fluctuaciones motoras de la enfermedad de Parkinson avanzada.Introduccion. La enfermedad de Parkinson (EP) avanzada conlleva complicaciones, como fluctuaciones motoras. Su atencion sanitaria en España se realiza frecuentemente en unidades de trastornos del movimiento (UTM). Objetivo. Conocer los recursos diagnosticos y el abordaje terapeutico de las UTM. Sujetos y metodos. Estudio descriptivo, transversal. Se diseño un cuestionario en linea, dirigido a neurologos de UTM, de 48 preguntas sobre recursos disponibles, numero de pacientes atendidos con EP y con fluctuaciones motoras, y abordaje terapeutico segun el estadio de Hoehn y Yahr (HY). Resultados. Participaron 55 neurologos. Disponen de neuroimagen estructural el 100%; neuroimagen funcional, el 89%; tests agudos farmacologicos, el 89%; tests geneticos, el 78%, y ecografia transcraneal, el 53%. Hay 2,5 neurologos y 1,2 enfermeras por unidad. Atienden a un 19% de pacientes con EP en estadio de HY 1, un 59% en estadio de HY 2-3 y un 22% en estadio de HY 4-5. Utilizan en primer lugar los inhibidores de la monoaminooxidasa B en los estadios de HY 1 y 2, y levodopa en los estadios de HY 3, 4 y 5. Un 24% de los pacientes tiene fluctuaciones motoras, con 5,5 episodios off diarios, de 44 minutos, con un total de siete horas off diarias. Un 14% de los pacientes de hasta 70 años con mas de tres episodios off diarios de larga duracion recibe tratamiento invasivo para las fluctuaciones motoras. Conclusiones. Las UTM estan bien dotadas de recursos diagnosticos y farmacologicos. Los tratamientos farmacologicos se individualizan con gran variedad de combinaciones. A pesar de esta optimizacion, la prevalencia de fluctuaciones motoras es todavia alta en pacientes avanzados, y las terapias invasivas pueden infrautilizarse.

Visual hallucinations in patients with acute stroke: a prospective exploratory study.

BACKGROUND AND PURPOSE: The incidence, underlying physiopathology, features and association with lesion topography of visual hallucinations in acute stroke have scarcely been investigated. METHODS: Patients with a diagnosis of acute stroke (ischaemic or haemorrhagic) in any vascular territory, admitted within 24 h after the onset of symptoms, were consecutively included in the study. Patients with a previous history of psychosis or cognitive impairment were excluded. They and/or their caregivers answered a structured hallucination and sleep questionnaire at admission, within the first 15 days and at the clinical follow-up 3-6 months after discharge. Lesion location (IMAIOS online atlas) and leukoaraiosis (Wahlund scale) were determined by magnetic resonance imaging or computed tomography scan. Subsets of patients also underwent a neuropsychological evaluation (N = 50) and an electroencephalogram (N = 33) before discharge. RESULTS: In all, 77 patients with a mean age of 71 ± 12 years were included of whom 57.1% were men. The incidence of visual hallucinations was 16.7%. These hallucinations were mostly complex, in black and white and self-limited. The appearance of hallucinations was not influenced by age, sex, neuropsychological performance during admission or modified Rankin scale score at discharge. Visual hallucinations were associated with occipital cortex lesions (P = 0.04), and with sleep disturbances during and before admission (P = 0.041 and P = 0.03 respectively). CONCLUSIONS: Visual hallucinations are relatively frequent in patients with acute stroke and they are self-limited. Patients with occipital lesions and sleep disturbances are more likely to suffer them.

[The essence of essential tremor: neurochemical bases]. / La esencia del temblor esencial: bases neuroquimicas.

INTRODUCTION: Essential tremor is the most frequent movement disorder in adults. It has been considered a benign disease, but can result in significant physical and psychosocial disability. Pharmacological treatment is still not very satisfactory. Its causation, pathophysiology and anatomy remain only partially understood. AIMS: An understanding of its neurochemical basis is essential to be able to develop more efficient therapies. We review what is currently known in this field in order to motivate further research and ideas that allow an enhanced understanding of the disease and which foster the development of new pharmacological therapies. DEVELOPMENT: We review the studies conducted to date in humans and in animal models of neurotransmitters (gamma-aminobutyric acid, glutamate, noradrenalin, serotonin, adenosine), proteins and other neurochemical phenomena, such as T-type calcium channels, in essential tremor. CONCLUSIONS: Four neurochemical dysfunctions have been described that basically occur in the cerebellum and the inferior olivary nucleus: alteration of the GABAergic system, increased post-inhibitory rebound via T-type calcium currents, decreased neuronal inhibition mechanisms and an increase in excitatory neurotransmitter activity. These neurochemical dysfunctions would involve an increase in the activity of the deep neurons of the cerebellum with an oscillatory activity that would shift to the thalamic nucleus and the motor cortex, which in turn would lead to the appearance of tremor. Further research is needed to be able to confirm these hypotheses and to continue to advance towards achieving more efficient pharmacological treatments for patients with essential tremor.

TITLE: La esencia del temblor esencial: bases neuroquimicas.Introduccion. El temblor esencial es el trastorno del movimiento mas frecuente en el adulto. Se ha considerado una enfermedad benigna, pero puede ocasionar una importante discapacidad fisica y psicosocial. El tratamiento farmacologico sigue siendo poco satisfactorio. Su etiologia, fisiopatologia y anatomia siguen sin conocerse del todo. Objetivo. El conocimiento de las bases neuroquimicas es fundamental para el desarrollo de terapias mas eficaces. Se revisan los conocimientos actuales en este campo a fin de incentivar nuevas investigaciones e ideas que permitan mejorar la comprension de la enfermedad y que fomenten el desarrollo de nuevas terapias farmacologicas. Desarrollo. Se revisan los trabajos realizados hasta la fecha en humanos y en modelos animales de neurotransmisores (acido gamma-aminobutirico, glutamato, noradrenalina, serotonina, adenosina), proteinas y otros fenomenos neuroquimicos, como los canales de calcio de tipo T en el temblor esencial. Conclusiones. Se han descrito cuatro disfunciones neuroquimicas que acontecerian basicamente en el cerebelo y el nucleo olivar inferior: alteracion del sistema gabergico, aumento del rebote postinhibitorio mediante corrientes de calcio de tipo T, disminucion de los mecanismos de inhibicion neuronal y aumento de la actividad de los neurotransmisores excitatorios. Estas disfunciones neuroquimicas comportarian un aumento de la actividad de las neuronas profundas cerebelosas con actividad oscilatoria, que se trasladaria al nucleo del talamo y a la corteza motora, y comportarian la aparicion del temblor. Son necesarios nuevos estudios para poder confirmar estas hipotesis y seguir avanzando para conseguir tratamientos farmacologicos mas eficaces para los pacientes con temblor esencial.

Fused in Sarcoma (FUS) gene mutations are not a frequent cause of essential tremor in Europeans.

FUS/TLS (denoting fused in sarcoma/translocated in liposarcoma [MIM 137070]) codifies an RNA binding protein. Mutations in this gene cause amyotrophic lateral sclerosis (ALS; MIM 608030). Essential tremor (ET [MIM 190300]) is the most frequent movement disorder. Despite its strong familiar aggregation, recently a whole exome sequencing study has identified FUS mutations as a cause of familial ET. To determine whether mutations in FUS are also common in other populations, we sequenced FUS gene in 178 unrelated Spanish subjects with ET. We detected only an intronic single-pair nucleotide deletion (c.1293-37delC), which was predicted to affect mRNA splicing. However, leukocyte mRNA analysis showed no changes in FUS expression. In conclusion, coding or splicing FUS mutations are not a frequent cause of ET in the Spanish population.

Gaba and serotonin molecular neuroimaging in essential tremor: a clinical correlation study.

BACKGROUND: Essential tremor is the most common movement disorder in adults, but its exact etiology and pathophysiology are still not fully understood. There is some consensus, however, about the involvement of the cerebellum and accumulating evidence points towards a dysfunction of the gabaergic system. We hypothesize that the serotonin neurotransmission system may also play a role as it does in tremor in Parkinson disease. This study aimed to investigate the association between the severity of tremor symptoms and the gabaergic and serotoninergic neurotransmission systems in essential tremor. MATERIAL AND METHODS: We measured the tremor clinical rating scale score and acquired DASB and Flumazenil PET scans in 10 patients who presented with essential tremor at different stages of clinical severity. Statistically significant correlations were sought between the scale scores and parametric binding potential images. RESULTS: The correlation analysis of cerebellar Flumazenil uptake and tremor clinical rating scale scores reached statistical significance (R2 = 0.423, p = 0.041), whereas no association was detected in the DASB scans. CONCLUSIONS: The severity of tremor correlated with the abnormalities found in GABA receptor binding, suggesting a primary gabaergic deficiency or a functional abnormality at the level of GABA(A) receptor subtypes. These results may assist in the rational development of new pharmacological treatments for essential tremor.

Motor changes during sertraline treatment in depressed patients with Parkinson's disease*.

BACKGROUND: Pharmacological interventions to treat depressive symptoms associated with Parkinson's disease (PD) are limited. Whether selective serotonine re-uptake inhibitors increase parkinsonism or have clinically significant interactions with antiparkinsonian drugs is unresolved. PURPOSE: We used a naturalistic approach to prospectively investigate the long-term effects on motor status of adding sertraline in a large sample of community-dwelling PD patients with depressive symptoms. METHODS: Main outcome measure was the motor part of the Unified PD Rating Scale (UPDRS) at baseline and at 1-, 3-, and 6-month follow-up. Secondary measures were the change in antiparkinsonian drugs expressed as total levodopa equivalent dose and the scores of the Hospital Anxiety and Depression Scale (HADS). Of the 374 patients included, 310 (82%) completed the study. RESULTS: Treatment with sertraline (mean dose 66.0 +/- 29.8 mg) resulted in improvement in all UPDRS domains along with a significant decrease of the HADS scores. A modest but significant increase of the total dose of levodopa, without significant change of total levodopa equivalent dose, was observed. Almost 8% of patients discontinued medication for adverse events, mainly related to the gastrointestinal system. CONCLUSIONS: Although worsening of tremor was observed in some patients, active management of depression with sertraline appears to have a positive impact on parkinsonism.

Lack of prefrontal repetitive transcranial magnetic stimulation effects in time production processing.

The aim of the present study was to determine the effects of high frequency repetitive transcranial magnetic stimulation (rTMS) over different neuroanatomical areas [left and right doroslateral prefrontal cortex (DLPFC) and right cerebellar hemisphere] on time production task. The study was performed in 16 healthy right-handed men with a cross-over, within subject repeated measures design. There were four rTMS conditions: baseline without stimulation, high frequency rTMS over right, left DLPFC and over right cerebellum. The volunteers were asked to produce a 3-min interval by internal counting. The rTMS was applied during the task. No significantly differences were observed in absolute error scores in time estimation task with any rTMS condition. This preliminary study does not support the role of the prefrontal lobe in time production processes.

Bilateral deep brain stimulation in Parkinson's disease: a multicentre study with 4 years follow-up.

Deep brain stimulation (DBS) is associated with significant improvement of motor complications in patients with severe Parkinson's disease after some 6-12 months of treatment. Long-term results in a large number of patients have been reported only from a single study centre. We report 69 Parkinson's disease patients treated with bilateral DBS of the subthalamic nucleus (STN, n = 49) or globus pallidus internus (GPi, n = 20) included in a multicentre study. Patients were assessed preoperatively and at 1 year and 3-4 years after surgery. The primary outcome measure was the change in the 'off' medication score of the Unified Parkinson's Disease Rating Scale motor part (UPDRS-III) at 3-4 years. Stimulation of the STN or GPi induced a significant improvement (50 and 39%; P < 0.0001) of the 'off' medication UPDRS-III score at 3-4 years with respect to baseline. Stimulation improved cardinal features and activities of daily living (ADL) (P < 0.0001 and P < 0.02 for STN and GPi, respectively) and prolonged the 'on' time spent with good mobility without dyskinesias (P < 0.00001). Daily dosage of levodopa was significantly reduced (35%) in the STN-treated group only (P < 0.001). Comparison of the improvement induced by stimulation at 1 year with 3-4 years showed a significant worsening in the 'on' medication motor states of the UPDRS-III, ADL and gait in both STN and GPi groups, and speech and postural stability in the STN-treated group. Adverse events (AEs) included cognitive decline, speech difficulty, instability, gait disorders and depression. These were more common in patients treated with DBS of the STN. No patient abandoned treatment as a result of these side effects. This experience, which represents the first multicentre study assessing the long-term efficacy of either STN or GPi stimulation, shows a significant and substantial clinically important therapeutic benefit for at least 3-4 years in a large cohort of patients with severe Parkinson's disease.

[Cognitive and functional decline in the stage previous to the diagnosis of Alzheimers disease]. / Deterioro cognitivo y funcional en la fase previa al diagnóstico de enfermedad de Alzheimer.

INTRODUCTION: The decline in the phase prior to diagnosis of Alzheimers disease (AD) is not well known, although this knowledge is necessary to evaluate the efficiency of new drugs that can influence in disease course prior to diagnosis. OBJECTIVE: To contribute to better knowledge of the decline prior to diagnosis, we have investigated the cognitive and functional deterioration for 2-3 years before the probable AD diagnosis was established. PATIENTS AND METHODS: We compared results obtained by 17 control subjects and 27 patients at the time of diagnosis of a probable AD with results obtained 2-3 years before (interval of 27.7 4 months). We compared memory functions (logical, recognition, learning and autobiographical memory), naming, visual and visuospatial gnosis, visuoconstructive praxis, verbal fluency and the Mini-Mental State Examination (MMSE), Informant Questionnaire and Blessed's Scale scores. RESULTS: Performance of control subjects did not change. AD patients showed a significant decline in scores, except for verbal fluency. In order of importance, cognitive decline was more marked in scores of learning memory, visuospatial gnosis, autobiographical memory and visuoconstructive praxis. CONCLUSIONS: Decline prior to diagnosis of AD is characterized by an important learning memory impairment. Deterioration of visuospatial gnosis and visuoconstructive praxis is greater than deterioration of MMSE and Informant Questionnaire scores.

Deterioro cognitivo y funcional en la fase previa al diagnóstico de enfermedad de Alzheimer / Cognitive and functional decline in the stage previous to the diagnosis of Alzheimer´s disease

Introducción: El deterioro en la fase previa al diagnóstico de enfermedad de Alzheimer (EA) no es bien conocido, a pesar de que este conocimiento es necesario a fin de evaluar la eficacia de nuevos fármacos que puedan ser capaces de incidir en el curso anterior al diagnóstico de la enfermedad. Objetivos: Con el ánimo de contribuir a un mejor conocimiento del deterioro previo al diagnóstico, hemos investigado el deterioro cognitivo y funcional acaecido en un período de al menos 2-3 años antes de que el diagnóstico de probable EA fuese establecido. Métodos: Comparamos los resultados obtenidos por 17 sujetos control y 27 pacientes en el momento de establecer el diagnóstico de probable EA con aquellos obtenidos de 2 a 3 años antes (intervalo promedio de 27,7ñ4 meses). Comparamos funciones mnésicas (memoria reciente lógica, de reconocimiento, de aprendizaje y autobiográfica), denominación, gnosis visuales y visuoespaciales, praxis visuoconstructivas, fluencias y las puntuaciones del Miniexamen del estado mental (MMSE), el Test del informador y la escala de Blessed. Resultados: Las puntuaciones obtenidas por los sujetos control no variaron. Las puntuaciones en los pacientes con EA empeoraron significativamente a excepción de las fluencias. El grado de deterioro cognitivo fue más acentuado, y por este orden, en las puntuaciones de memoria de aprendizaje, gnosis visuoespaciales, memoria autobiográfica y praxis visuoconstructiva. Conclusiones: El deterioro previo al diagnóstico de EA está caracterizado por una marcada afectación de la memoria de aprendizaje. Funciones como la gnosis visuoespacial y la praxis visuoconstructiva se deterioran en mayor medida que lo que decrece la puntuación global en el MMSE o lo que aumenta la puntuación en el Test del informador (AU)

Effects of repetitive transcranial magnetic stimulation on memory subtypes: a controlled study.

Repetitive transcranial magnetic stimulation (rTMS) of human cortex may disrupt or facilitate cortical activity. The aim of the present study was to investigate the consequences of rTMS applied over different cortical areas during various memory tasks, measuring immediate, working and episodic verbal memory. The study was performed in 16 right-handed healthy men. A double-blind, cross-over, within-subject repeated measures design was used. There were five rTMS conditions: baseline without stimulation, high frequency (HF) rTMS over right and left dorsolateral prefrontal cortex (DLPFC) and over right cerebellum, and low frequency (LF) parameters over left DLPFC. Digits forwards and backwards and letter-number sequencing of the Wechsler Adults Intelligence Scale (WAIS) were used to assess immediate and working verbal memory, and logical memory of the Rivermead Behavioural Memory Test was used to assess episodic memory encoding. An analysis of variance (ANOVA) for repeated measures in the scores of each memory task according to rTMS conditions was used. Significantly lower scores in the number of memory units of the episodic memory task were observed when rTMS high frequency parameters were applied over left DLPFC (P=0.009). No significant differences were found in the other memory subtype tasks analysed during the different rTMS conditions. These findings provide evidence for the significant role of the left DLPFC in episodic verbal memory processes.

[Validation of the translation to Catalan and Spanish of cognitive evoked potential N400]. / Validación de la traducción a los idiomas catalán y castellano del potencial evocado cognitivo N400.

INTRODUCTION: The cognitive evoked potential N400 permits an objective assessment of the verbal semantic processing. It has been suspected to be clinically useful in cognitive abnormalities and a correlation with attentional and memory functions has been found. The present study tries to validate the translation and adaptation of the English paradigm to the Catalan and Spanish languages. METHOD: The study was performed on 16 healthy volunteers with Catalan native language and 16 volunteers with Spanish native language. Three blocks of 50 sentences (4-9 words) were administered using headphones. The last word of 50 % of the sentences was incongruent. The beginning of this word was the trigger for the EEG average. EEG leads used were: Fz, Cz, Pz, C3, C4, T3, T4 with biauricular reference. The measures were amplitude and latency of the potential obtained after the subtraction of the EEG average of congruent and incongruent sentences. A t-test for one sample (the original potential) was applied. RESULTS: Amplitude and latency of the potential obtained by the Catalan and Spanish languages were not result statistically different from the original potential. The major amplitude was obtained in Cz. Mean amplitudes: Catalan language: 5.3 2.3 V (95 % CI for the difference: 0.39 2.12 V); Spanish language: 5.2 2.3 V (95 % CI for the difference: 0.43 2.32 V). CONCLUSIONS: The Catalan and Spanish version of the N400 evoked potential offer the possibility to use an objective instrument for the study of language in neuroscience.

Validación de la traducción a los idiomas catalán y castellano del potencial evocado cognitivo N400 / Validation of the translation to Catalan and Spanish of cognitive evoked potential N400

Introducción: El potencial evocado cognitivo N400 permite una valoración objetiva del procesamiento verbal semántico. Se ha postulado su utilidad en el estudio del deterioro cognitivo, habiéndose correlacionado con funciones atencionales, mnésicas y de dominancia hemisférica. El presente estudio intenta validar la traducción y adaptación a los idiomas catalán y castellano del paradigma original en inglés.Método: Participaron en el estudio 16 voluntarios sanos de sexo masculino con idioma materno catalán y 16 voluntarios con idioma materno castellano. Se administraron mediante auriculares 3 bloques de 50 frases (4-9 palabras). El 50 por ciento de las frases contenían la última palabra incongruente.El inicio de esta palabra era el marcador del promediado del electroencefalograma (EEG). Derivaciones EEG: Fz, Cz, Pz, C3, C4, T3, T4 con referencia biauricular. Se valoró la amplitud y latencia del potencial obtenido después de la sustracción del promediado EEG de las frases congruentes e incongruentes.Se aplicó un test de la t de Student para una sola muestra respecto al potencial original.Resultados: La amplitud y latencia del potencial obtenido para los idiomas catalán y castellano no resultaron significativamente diferentes respecto al potencial original. El potencial de mayor amplitud se obtuvo en Cz. Amplitud media: idioma catalán, 5,3 ñ 2,3 µV (intervalo de confianza [IC] 95 por ciento para la diferencia: -0,39 ñ2,12 µV); idioma castellano, 5,2 ñ 2,3 µV (IC 95 por ciento para la diferencia: -0,43 ñ2,32 µV).Conclusión: Las versiones catalana y castellana del potencial N400 ofrecen la posibilidad de usar un instrumento objetivo para el estudio del lenguaje en el campo de las neurociencias (AU)

Atención sostenida en la fase preclínica de la enfermedad de Alzheimer / Sustained attention in the preclinical phase of Alzheimer´s disease

Introducción. El deterioro atencional en la fase preclínica de la demencia de tipo Alzheimer (DTA) no se conoce bien, ni los estudios disponibles son concluyentes. Objetivo. Planteamos la posibilidad de identificar un trastorno de la atención sostenida en la fase preclínica de la DTA y explorar si este trastorno ayudaría a identificar a aquellos pacientes que, remitidos inicialmente por quejas subjetivas de pérdida de memoria (QSPM), involucionarán en pocos años a DTA. Pacientes y métodos. Comparamos la exploración inicial en una prueba de atención sostenida (CPT) de 70 pacientes remitidos por QSPM, de los cuales 27 involucionaron a DTA en el plazo de 2 años y 43 permanecieron estables. Resultados. Los pacientes que involucionaron presentaron, 2 años antes de su diagnóstico, rendimientos significativamente inferiores a aquellos otros que no involucionaron. Cometieron un mayor número de errores de omisión y obtuvieron un menor número de aciertos. Conclusiones. La prueba de vigilancia tipo CPT es capaz de detectar el deterioro de atención sotenida en la fase preclínica de la DTA y podría ser un indicador objetivo del declinar cognitivo en la fase preclínica de la enfermedad de Alzheimer (AU)

Introduction. Deterioration of attention in the preclinical phase of dementia of Alzheimer’s type (DAT) is not very well-known neither available studies are conclusive. Objective. We outline if would be possible to identify a deficit of sustained attention in preclinical phase of DAT and if this attentional dysfunction could help to identify those patients, referred by subjective memory complaints (SMC), who will progress in a few years to DAT. Patients and methods. We compared basal exploration in a task of sustained attention (CPT) of 70 patients referred by SMC and followed longitudinally for 2 years. Twenty-seven patients developed probable DAT and forty-three remained clinically stable. Results. Patients who will be diagnosed 2 years later with DAT performed significantly more poorly than patients who did not develop DAT. Patients who will be diagnosed 2 years later with DAT made a higher number of omission errors and obtained a lower number of correct responses. Conclusion. CPT paradigm is a vigilance task that detects deterioration of sustained attention in the preclinical phase of DAT and could be an objective indicator of the cognitive decline in the preclinical phase of Alzheimer’s disease (AU)