Sensory Attenuation Assessed by Sensory Evoked Potentials in Functional Movement Disorders.

BACKGROUND: Functional (psychogenic) movement disorders (FMD) have features associated with voluntary movement (e.g. distractibility) but patients report movements to be out of their control. One explanation for this phenomenon is that sense of agency for movement is impaired. The phenomenon of reduction in the intensity of sensory experience when movement is self-generated and a reduction in sensory evoked potentials (SEPs) amplitude at the onset of self-paced movement (sensory attenuation) have been linked to sense of agency for movement. METHODS: We compared amplitude of SEPs from median nerve stimulation at rest and at the onset of a self-paced movement of the thumb in 17 patients with FMD and 17 healthy controls. RESULTS: Patients showed lack of attenuation of SEPs at the onset of movement compared to reduction in amplitude of SEPs in controls. FMD patients had significantly different ratios of movement onset to rest SEPs than did healthy controls at each electrode: 0.79 in healthy controls and 1.35 in patients at F3 (t = -4.22, p<0.001), 0.78 in healthy controls and 1.12 at patients C3 (t = -3.15, p = 0.004) and 0.77 in healthy controls and 1.05 at patients P3 (t = -2.88, p = 0.007). CONCLUSIONS: Patients with FMD have reduced sensory attenuation as measured by SEPs at onset of self-paced movement. This finding can be plausibly linked to impairment of sense of agency for movement in these patients

Normal motor adaptation in cervical dystonia: a fundamental cerebellar computation is intact

The potential role of the cerebellum in the pathophysiology of dystonia has become a focus of recent research. However, direct evidence for a cerebellar contribution in humans with dystonia is difficult to obtain. We examined motor adaptation, a test of cerebellar function, in 20 subjects with primary cervical dystonia and an equal number of aged matched controls. Adaptation to both visuomotor (distorting visual feedback by 30°) and forcefield (applying a velocity-dependent force) conditions were tested. Our hypothesis was that cerebellar abnormalities observed in dystonia research would translate into deficits of cerebellar adaptation. We also examined the relationship between adaptation and dystonic head tremor as many primary tremor models implicate the cerebellothalamocortical network which is specifically tested by this motor paradigm. Rates of adaptation (learning) in cervical dystonia were identical to healthy controls in both visuomotor and forcefield tasks. Furthermore, the ability to adapt was not clearly related to clinical features of dystonic head tremor. We have shown that a key motor control function of the cerebellum is intact in the most common form of primary dystonia. These results have important implications for current anatomical models of the pathophysiology of dystonia. It is important to attempt to progress from general statements that implicate the cerebellum to a more specific evidence-based model. The role of the cerebellum in this enigmatic disease perhaps remains to be proven

Differential phenotypic expression of a novel PDHA1 mutation in a female monozygotic twin pair

Pyruvate dehydrogenase complex (PDC) deficiency caused by mutations in the X-linked PDHA1 gene has a broad clinical presentation, and the pattern of X-chromosome inactivation has been proposed as a major factor contributing to its variable expressivity in heterozygous females. Here, we report the first set of monozygotic twin females with PDC deficiency, caused by a novel, de novo heterozygous missense mutation in exon 11 of PDHA1 (NM_000284.3: c.1100A>T). Both twins presented in infancy with a similar clinical phenotype including developmental delay, episodes of hypotonia or encephalopathy, epilepsy, and slowly progressive motor impairment due to pyramidal, extrapyramidal, and cerebellar involvement. However, they exhibited clear differences in disease severity that correlated well with residual PDC activities (approximately 60% and 20% of mean control values, respectively) and levels of immunoreactive E1α subunit in cultured skin fibroblasts. To address whether the observed clinical and biochemical differences could be explained by the pattern of X-chromosome inactivation, we undertook an androgen receptor assay in peripheral blood. In the less severely affected twin, a significant bias in the relative activity of the two X chromosomes with a ratio of approximately 75:25 was detected, while the ratio was close to 50:50 in the other twin. Although it may be difficult to extrapolate these results to other tissues, our observation provides further support to the hypothesis that the pattern of X-chromosome inactivation may influence the phenotypic expression of the same mutation in heterozygous females and broadens the clinical and genetic spectrum of PDC deficiency

Differential phenotypic expression of a novel PDHA1 mutation in a female monozygotic twin pair.

Pyruvate dehydrogenase complex (PDC) deficiency caused by mutations in the X-linked PDHA1 gene has a broad clinical presentation, and the pattern of X-chromosome inactivation has been proposed as a major factor contributing to its variable expressivity in heterozygous females. Here, we report the first set of monozygotic twin females with PDC deficiency, caused by a novel, de novo heterozygous missense mutation in exon 11 of PDHA1 (NM_000284.3: c.1100A>T). Both twins presented in infancy with a similar clinical phenotype including developmental delay, episodes of hypotonia or encephalopathy, epilepsy, and slowly progressive motor impairment due to pyramidal, extrapyramidal, and cerebellar involvement. However, they exhibited clear differences in disease severity that correlated well with residual PDC activities (approximately 60% and 20% of mean control values, respectively) and levels of immunoreactive E1α subunit in cultured skin fibroblasts. To address whether the observed clinical and biochemical differences could be explained by the pattern of X-chromosome inactivation, we undertook an androgen receptor assay in peripheral blood. In the less severely affected twin, a significant bias in the relative activity of the two X chromosomes with a ratio of approximately 75:25 was detected, while the ratio was close to 50:50 in the other twin. Although it may be difficult to extrapolate these results to other tissues, our observation provides further support to the hypothesis that the pattern of X-chromosome inactivation may influence the phenotypic expression of the same mutation in heterozygous females and broadens the clinical and genetic spectrum of PDC deficiency

A Critical Investigation of Cerebellar Associative Learning in Isolated Dystonia.

BACKGROUND: Impaired eyeblink conditioning is often cited as evidence for cerebellar dysfunction in isolated dystonia yet the results from individual studies are conflicting and underpowered. OBJECTIVE: To systematically examine the influence of dystonia, dystonia subtype, and clinical features over eyeblink conditioning within a statistical model which controlled for the covariates age and sex. METHODS: Original neurophysiological data from all published studies (until 2019) were shared and compared to an age- and sex-matched control group. Two raters blinded to participant identity rescored all recordings (6732 trials). After higher inter-rater agreement was confirmed, mean conditioning per block across raters was entered into a mixed repetitive measures model. RESULTS: Isolated dystonia (P = 0.517) and the subtypes of isolated dystonia (cervical dystonia, DYT-TOR1A, DYT-THAP1, and focal hand dystonia) had similar levels of eyeblink conditioning relative to controls. The presence of tremor did not significantly influence levels of eyeblink conditioning. A large range of eyeblink conditioning behavior was seen in both health and dystonia and sample size estimates are provided for future studies. CONCLUSIONS: The similarity of eyeblink conditioning behavior in dystonia and controls is against a global cerebellar learning deficit in isolated dystonia. Precise mechanisms for how the cerebellum interplays mechanistically with other key neuroanatomical nodes within the dystonic network remains an open research question. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society

Management of Parkinson's disease and other movement disorders in women of childbearing age: Part 2

[spa] 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 Espanola ˜ 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. [eng] 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 women of childbearing age: Part 2

[ES] 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.[EN] 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

[ES] 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.[EN] 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