RESUMEN
Huntington's Disease (HD) is an autosomal neurodegenerative disease characterized by motor, cognitive, and psychiatric symptoms. Cognitive impairment develops gradually in HD patients, progressing later into a severe cognitive dysfunction. The Montreal Cognitive Assessment (MoCA) is a brief screening test commonly employed to detect mild cognitive impairment, which has also been useful to assess cognitive decline in HD patients. However, the relationship between MoCA performance and brain structural integrity in HD patients remains unclear. Therefore, to explore this relationship we analyzed if cortical thinning and subcortical nuclei volume differences correlated with HD patients' MoCA performance. Twenty-two HD patients and twenty-two healthy subjects participated in this study. T1-weighted images were acquired to analyze cortical thickness and subcortical nuclei volumes. Group comparison analysis showed a significantly lower score in the MoCA global performance of HD patients. Also, the MoCA total score correlated with cortical thinning of fronto-parietal and temporo-occipital cortices, as well as with bilateral caudate volume differences in HD patients. These results provide new insights into the effectiveness of using the MoCA test to detect cognitive impairment and the brain atrophy pattern associated with the cognitive status of prodromal/early HD patients.
Asunto(s)
Enfermedad de Huntington , Enfermedades Neurodegenerativas , Humanos , Enfermedad de Huntington/complicaciones , Enfermedades Neurodegenerativas/complicaciones , Adelgazamiento de la Corteza Cerebral , Pruebas de Estado Mental y Demencia , Atrofia/complicacionesRESUMEN
The cerebellar cognitive affective syndrome (CCAS) has been consistently described in patients with acute/subacute cerebellar injuries. However, studies with chronic patients have had controversial findings that have not been explored with new cerebellar-target tests, such as the CCAS scale (CCAS-S). The objective of this research is to prove and contrast the usefulness of the CCAS-S and the Montreal Cognitive Assessment (MoCA) test to evaluate cognitive/affective impairments in patients with chronic acquired cerebellar lesions, and to map the cerebellar areas whose lesions correlated with dysfunctions in these tests. CCAS-S and MoCA were administrated to 22 patients with isolated chronic cerebellar strokes and a matched comparison group. The neural bases underpinning both tests were explored with multivariate lesion-symptom mapping (LSM) methods. MoCA and CCAS-S had an adequate test performance with efficient discrimination between patients and healthy volunteers. However, only impairments determined by the CCAS-S resulted in significant regional localization within the cerebellum. Specifically, patients with chronic cerebellar lesions in right-lateralized posterolateral regions manifested cognitive impairments inherent to CCAS. These findings concurred with the anterior-sensorimotor/posterior-cognitive dichotomy in the human cerebellum and revealed clinically intra- and cross-lobular significant regions (portions of right lobule VI, VII, Crus I-II) for verbal tasks that overlap with the "language" functional boundaries in the cerebellum. Our findings prove the usefulness of MoCA and CCAS-S to reveal cognitive impairments in patients with chronic acquired cerebellar lesions. This study extends the understanding of long-term CCAS and introduces multivariate LSM methods to identify clinically intra- and cross-lobular significant regions underpinning chronic CCAS.
Asunto(s)
Enfermedades Cerebelosas , Trastornos del Conocimiento , Accidente Cerebrovascular , Cerebelo , Cognición , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/patología , Humanos , Imagen por Resonancia Magnética , Accidente Cerebrovascular/complicacionesRESUMEN
BACKGROUND: Spinocerebellar ataxia type 10 is a neurodegenerative disorder caused by the expansion of an ATTCT pentanucleotide repeat. Its clinical features include ataxia and, in some cases, epileptic seizures. There is, however, a dearth of information about its cognitive deficits and the neural bases underpinning them. OBJECTIVES: The objectives of this study were to characterize the performance of spinocerebellar ataxia type 10 patients in 2 cognitive domains typically affected in spinocerebellar ataxias, memory and executive function, and to correlate the identified cognitive impairments with ataxia severity and cerebral/cerebellar cortical thickness, as quantified by MRI. METHODS: Memory and executive function tests were administered to 17 genetically confirmed Mexican spinocerebellar ataxia type 10 patients, and their results were compared with 17 healthy matched volunteers. MRI was performed in 16 patients. RESULTS: Patients showed deficits in visual and visuospatial short-term memory, reduced storage capacity for verbal memory, and impaired monitoring, planning, and cognitive flexibility, which were ataxia independent. Patients with seizures (n = 9) and without seizures (n = 8) did not differ significantly in cognitive performance. There were significant correlations between short-term visuospatial memory impairment and posterior cerebellar lobe cortical thickness (bilateral lobule VI, IX, and right X). Cognitive flexibility deficiencies correlated with cerebral cortical thickness in the left middle frontal, cingulate, opercular, and temporal gyri. Cerebellar cortical thickness in several bilateral regions was correlated with motor impairment. CONCLUSIONS: Patients with spinocerebellar ataxia type 10 show significant memory and executive dysfunction that can be correlated with deterioration in the posterior lobe of the cerebellum and prefrontal, cingulate, and middle temporal cortices. © 2021 International Parkinson and Movement Disorder Society.
Asunto(s)
Disfunción Cognitiva , Ataxias Espinocerebelosas , Cerebelo , Corteza Cerebral/diagnóstico por imagen , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/etiología , Humanos , Imagen por Resonancia Magnética , Memoria a Corto Plazo , Pruebas Neuropsicológicas , Ataxias Espinocerebelosas/complicaciones , Ataxias Espinocerebelosas/diagnóstico por imagen , Ataxias Espinocerebelosas/genéticaRESUMEN
Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disease characterized by progressive ataxia and retinal degeneration. Previous cross-sectional studies show a significant decrease in the gray matter of the cerebral cortex, cerebellum, and brainstem. However, there are no longitudinal studies in SCA7 analyzing whole-brain degeneration and its relation to clinical decline. To perform a 2-year longitudinal characterization of the whole-brain degeneration and clinical decline in SCA7, twenty patients underwent MRI and clinical evaluations at baseline. Fourteen completed the 2-year follow-up study. A healthy-matched control group was also included. Imaging analyses included volumetric and cortical thickness evaluation. We measured the cognitive deterioration in SCA7 patients using MoCA test and the motor deterioration using the SARA score. We found statistically significant differences in the follow-up compared to baseline. Imaging analyses showed that SCA7 patients had severe cerebellar and pontine degeneration compared with the control group. Longitudinal follow-up imaging analyses of SCA7 patients showed the largest atrophy in the medial temporal lobe without signs of a progression of cerebellar and pontine atrophy. Effect size analyses showed that MRI longitudinal analysis has the largest effect size followed by the SARA scale and MoCA test. Here, we report that it is possible to detect significant brain atrophy and motor and cognitive clinical decline in a 2-year follow-up study of SCA7 patients. Our results support the hypothesis that longitudinal analysis of structural MRI and MOCA tests are plausible clinical markers to study the natural history of the disease and to design treatment trials in ecologically valid contexts.
Asunto(s)
Sustancia Gris/diagnóstico por imagen , Enfermedades Neurodegenerativas/diagnóstico por imagen , Ataxias Espinocerebelosas/diagnóstico por imagen , Adolescente , Adulto , Atrofia , Encéfalo/patología , Encéfalo/fisiopatología , Cerebelo/diagnóstico por imagen , Corteza Cerebral/diagnóstico por imagen , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Sustancia Gris/fisiopatología , Humanos , Procesamiento de Imagen Asistido por Computador , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Pruebas de Estado Mental y Demencia , Persona de Mediana Edad , Enfermedades Neurodegenerativas/fisiopatología , Puente/diagnóstico por imagen , Ataxias Espinocerebelosas/fisiopatología , Aprendizaje Verbal , Adulto JovenRESUMEN
INTRODUCTION: Spinocerebellar ataxia type 10 (SCA10) is a hereditary neurodegenerative disorder caused by repeat expansions in the ATXN10 gene. Patients present with cerebellar ataxia frequently accompanied by seizures. Even though loss of cerebellar Purkinje neurons has been described, its brain degeneration pattern is unknown. Our aim was to characterize the gray and white matter degeneration patterns in SCA10 patients and the association with clinical features. METHODS: We enrolled 18 patients with molecular diagnosis of SCA10 and 18 healthy individuals matched for age and sex. All participants underwent brain MRI including high-resolution anatomical and diffusion images. Whole-brain Tract-Based Spatial Statistics (TBSS) and Voxel-Based Morphometry (VBM) were performed to identify white and grey matter degeneration respectively. A second analysis in the cerebellum identified the unbiased pattern of degeneration. Motor impairment was assessed using the SARA Scale. RESULTS: TBSS analysis in the patient group revealed white matter atrophy exclusively in the cerebellum. VBM analysis showed extensive grey matter degeneration in the cerebellum, brainstem, thalamus, and putamen. Significant associations between cerebellar degeneration and SARA scores were found. Additionally, degeneration in thalamic GM and WM in the cerebellar lobule VI were significantly associated with the presence of seizures. CONCLUSION: The results show that besides cerebellum and brainstem, brain degeneration in SCA10 includes predominantly the putamen and thalamus; involvement of the latter is strongly associated with seizures. Analysis of the unbiased degeneration pattern in the cerebellum suggests lobules VIIIb, IX, and X as the primary cerebellar targets of the disease, which expands to the anterior lobe in later stages.
Asunto(s)
Cerebelo/patología , Sustancia Gris/patología , Putamen/patología , Ataxias Espinocerebelosas/patología , Tálamo/patología , Sustancia Blanca/patología , Adulto , Cerebelo/diagnóstico por imagen , Expansión de las Repeticiones de ADN , Femenino , Sustancia Gris/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Linaje , Putamen/diagnóstico por imagen , Ataxias Espinocerebelosas/diagnóstico por imagen , Tálamo/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagenRESUMEN
Different processes are involved during visuomotor learning, including an error-based procedural and a strategy based cognitive mechanism. Our objective was to analyze if the changes in the adaptation or the aftereffect components of visuomotor learning measured across development, reflected different maturation rates of the aforementioned mechanisms. Ninety-five healthy children aged 4-12years and a group of young adults participated in a wedge prism and a dove prism throwing task, which laterally displace or horizontally reverse the visual field respectively. The results show that despite the age-related differences in motor control, all children groups adapted in the error-based wedge prisms condition. However, when removing the prism, small children showed a slower aftereffects extinction rate. On the strategy-based visual reversing task only the older children group reached adult-like levels. These results are consistent with the idea of different mechanisms with asynchronous maturation rates participating during visuomotor learning.
Asunto(s)
Atención , Desarrollo Infantil , Desempeño Psicomotor , Adulto , Niño , Preescolar , Formación de Concepto , Extinción Psicológica , Femenino , Efecto Tardío Figurativo , Humanos , Masculino , Distorsión de la Percepción , Campos Visuales , Adulto JovenRESUMEN
BACKGROUND: Previous studies of SCA2 have revealed significant degeneration of white matter tracts in cerebellar and cerebral regions. The motor deficit in these patients may be attributable to the degradation of projection fibers associated with the underlying neurodegenerative process. However, this relationship remains unclear. Statistical analysis of diffusion tensor imaging enables an unbiased whole-brain quantitative comparison of the diffusion proprieties of white matter tracts in vivo. METHODS: Fourteen genetically confirmed SCA2 patients and aged-matched healthy controls participated in the study. Tract-based spatial statistics were performed to analyze structural white matter damage using two different measurements: fractional anisotropy (FA) and mean diffusivity (MD). Significant diffusion differences were correlated with the patient's ataxia impairment. RESULTS: Our analysis revealed decreased FA mainly in the inferior/middle/superior cerebellar peduncles, the bilateral posterior limb of the internal capsule and the bilateral superior corona radiata. Increases in MD were found mainly in cerebellar white matter, medial lemniscus, and middle cerebellar peduncle, among other regions. Clinical impairment measured with the SARA score correlated with FA in superior parietal white matter and bilateral anterior corona radiata. Correlations with MD were found in cerebellar white matter and the middle cerebellar peduncle. CONCLUSION: Our findings show significant correlations between diffusion measurements in key areas affected in SCA2 and measures of motor impairment, suggesting a disruption of information flow between motor and sensory-integration areas. These findings result in a more comprehensive view of the clinical impact of the white matter degeneration in SCA2.
Asunto(s)
Ataxia/diagnóstico , Ataxia/patología , Sustancia Blanca/patología , Adulto , Estudios de Casos y Controles , Imagen de Difusión por Resonancia Magnética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: To evaluate the effect of age-related cognitive changes in a visuomotor learning task that depends on strategic control and contrast it with the effect in a task principally depending on visuomotor recalibration. METHODS: Participants performed a ball throwing task while donning either a reversing dove prism or a displacement wedge prism, which mainly depend on strategic control or visuomotor recalibration, respectively. Visuomotor performance was then analysed in relation to rule acquisition and reversal, recognition memory, visual memory, spatial planning, and spatial working memory with tasks from the Cambridge Neuropsychological Test Automated Battery (CANTAB). RESULTS: The results confirmed previous works showing a detrimental effect of age on visuomotor learning. The analyses of the cognitive changes observed across age showed that both strategic control and visuomotor recalibration had significant negative correlations only with the number of errors in the spatial working memory task. However, when the effect of aging was controlled, the only significant correlation remaining was between the reversal adaptation magnitude and spatial working memory. DISCUSSION: These results suggest that spatial working memory decline across aging could contribute to age-dependent deterioration in both visuomotor learning processes. However, spatial working memory integrity seems to affect strategic learning decline even after controlling for aging.
Asunto(s)
Envejecimiento/fisiología , Aprendizaje/fisiología , Memoria a Corto Plazo/fisiología , Desempeño Psicomotor/fisiología , Memoria Espacial/fisiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
There are different kinds of visuomotor learnings. One of the most studied is error-based learning where the information about the sign and magnitude of the error is used to update the motor commands. However, there are other instances where subjects show visuomotor learning even if the use of error sign and magnitude information is precluded. In those instances subjects could be using strategic instead of procedural adaptation mechanisms. Here, we present the results of the effect of aging on visuomotor strategic learning under a reversed error feedback condition, and its contrast with procedural visuomotor learning within the same participants. A number of measures were obtained from a task consisting of throwing clay balls to a target before, during and after wearing lateral displacing or reversing prisms. The displacing prism results show an age dependent decrease on the learning rate that corroborates previous findings. The reversing prism results also show significant adaptation impairment in the aged population. However, decreased reversing learning in the older group was the result of an increase in the number of subjects that could not adapt to the reversing prism, and not on a reduction of the learning capacity of all the individuals of the group. These results suggest a significant deleterious effect of aging on visuomotor strategic learning implementation.
Asunto(s)
Envejecimiento/fisiología , Aprendizaje/fisiología , Desempeño Psicomotor/fisiología , Percepción Visual/fisiología , Adaptación Fisiológica , Adolescente , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Estimulación Luminosa , Adulto JovenRESUMEN
Our goal was to improve spinocerebellar ataxia type 2 (SCA2) cognitive profile characterization by testing the hypothesis that strategy, planning and rule acquisition capacities are affected in SCA2. Forty one patients with SCA2 were evaluated with the Spatial Working Memory (SWM), the Stockings of Cambridge (SOC), and the Intra-Extra Dimensional Shift (IED) tests of the Executive module of the Cambridge Neuropsychological Testing Automated Battery (CANTAB). Paired Associates Learning (PAL) and Delayed Matching to Sample (DMS) from the CANTAB memory module were also assessed to corroborate previous findings. Motor deterioration was measured using the Scale for the Assessment and Rating of Ataxia (SARA). We found significant SCA2 related deficits in strategy, planning, and rule acquisition. Our results also corroborated significant memory deficits in these patients with SCA2. Further analysis also showed that patients with large motor deterioration had poorer associative learning and spatial planning scores. Patients with SCA2 show strategy, planning, and rule acquisition deficits as revealed with the CANTAB battery. These deficits should be noted when planning an effective therapy for these patients.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/etiología , Trastornos del Conocimiento/etiología , Trastornos de la Memoria/etiología , Ataxias Espinocerebelosas/complicaciones , Adulto , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastornos del Conocimiento/diagnóstico , Expansión de las Repeticiones de ADN/genética , Femenino , Humanos , Masculino , Trastornos de la Memoria/diagnóstico , Escala del Estado Mental , Persona de Mediana Edad , Actividad Motora , Pruebas Neuropsicológicas , Índice de Severidad de la Enfermedad , Ataxias Espinocerebelosas/genética , Adulto JovenRESUMEN
Spinocerebellar Ataxia Type 2 (SCA2) is a genetic disorder causing cerebellar degeneration that result in motor and cognitive alterations. Voxel-based morphometry (VBM) analyses have found neurodegenerative patterns associated to SCA2, but they show some discrepancies. Moreover, behavioral deficits related to non-cerebellar functions are scarcely discussed in those reports. In this work we use behavioral and cognitive tests and VBM to identify and confirm cognitive and gray matter alterations in SCA2 patients compared with control subjects. Also, we discuss the cerebellar and non-cerebellar functions affected by this disease. Our results confirmed gray matter reduction in the cerebellar vermis, pons, and insular, frontal, parietal and temporal cortices. However, our analysis also found unreported loss of gray matter in the parahippocampal gyrus bilaterally. Motor performance test ratings correlated with total gray and white matter reductions, but executive performance and clinical features such as CAG repetitions and disease progression did not show any correlation. This pattern of cerebellar and non-cerebellar morphological alterations associated with SCA2 has to be considered to fully understand the motor and non-motor deficits that include language production and comprehension and some social skill changes that occur in these patients.
Asunto(s)
Encéfalo/patología , Interpretación de Imagen Asistida por Computador , Imagen por Resonancia Magnética , Ataxias Espinocerebelosas/patología , Ataxias Espinocerebelosas/psicología , Adulto , Cerebelo/patología , Corteza Cerebral/patología , Cognición , Femenino , Sustancia Gris/patología , Humanos , Masculino , Persona de Mediana Edad , Actividad Motora , Puente/patología , Pruebas PsicológicasRESUMEN
The prodromal phase of spinocerebellar ataxias (SCAs) has not been systematically studied. Main findings come from a homogeneous SCA type 2 (SCA2) population living in Cuba. The aim of this study was to characterize extensively the prodromal phase of SCA2 by several approaches. Thirty-seven non-ataxic SCA2 mutation carriers and its age- and sex-matched controls underwent clinical assessments, including standardized neurological exam, structured interviews and clinical scales, and looking for somatic and autonomic features, as well as a neuropsychological battery, antisaccadic recordings, and MRI scans. Main clinical somatic features of non-ataxic mutation carriers were cramps, sensory symptoms, sleep disorders, and hyperreflexia, whereas predominating autonomic symptoms were pollakiuria/nocturia, constipation, and frequent throat clearing. Cognitive impairments included early deficits of executive functions and visual memory, suggesting the involvement of cerebro-cerebellar-cerebral loops and/or reduced cholinergic basal forebrain input to the cortex. Antisaccadic task revealed impaired oculomotor inhibitory control but preserved ability for error correction. Cognitive and antisaccadic deficits were higher as carriers were closer to the estimated onset of ataxia, whereas higher Scale for the Assessment and Rating of Ataxia (SARA) scores were associated most notably to vermis atrophy. The recognition of early features of SCA2 offers novel insights into the prodromal phase and physiopathological base of the disease, allowing the assessment of its progression and the efficacy of treatments, in particular at early phases when therapeutical options should be most effective.
Asunto(s)
Ataxias Espinocerebelosas/epidemiología , Ataxias Espinocerebelosas/fisiopatología , Adulto , Anciano , Ataxinas , Encéfalo/patología , Encéfalo/fisiopatología , Trastornos del Conocimiento/epidemiología , Trastornos del Conocimiento/genética , Trastornos del Conocimiento/patología , Trastornos del Conocimiento/fisiopatología , Cuba/epidemiología , Medidas del Movimiento Ocular , Femenino , Humanos , Entrevistas como Asunto , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Mutación , Proteínas del Tejido Nervioso/genética , Examen Neurológico , Pruebas Neuropsicológicas , Síntomas Prodrómicos , Movimientos Sacádicos , Índice de Severidad de la Enfermedad , Ataxias Espinocerebelosas/genética , Ataxias Espinocerebelosas/patología , Adulto JovenRESUMEN
There are different types of visuomotor learning. Among the most studied is motor error-based learning where the sign and magnitude of the error are used to update motor commands. However, there are other instances where individuals show visuomotor learning even if the sign or magnitude of the error is precluded. Studies with patients suggest that the former learning is impaired after cerebellar lesions, while basal ganglia lesions disrupt the latter. Nevertheless, the cerebellar role is not restricted only to error-based learning, but it also contributes to several cognitive processes. Therefore, here, we tested if cerebellar ataxia patients are affected in two tasks, one that depends on error-based learning and the other that prevents the use of error-based learning. Our results showed that cerebellar patients have deficits in both visuomotor tasks; however, while error-based learning tasks deficits correlated with the motor impairments, the motor error-dependent task did not correlate with any motor measure.
Asunto(s)
Discapacidades para el Aprendizaje/etiología , Actividad Motora/fisiología , Trastornos de la Percepción/etiología , Desempeño Psicomotor/fisiología , Ataxias Espinocerebelosas/complicaciones , Percepción Visual/fisiología , Adaptación Fisiológica , Adulto , Ganglios Basales/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Campos Visuales/fisiologíaRESUMEN
Nerve conduction is profoundly affected in Spinocerebellar ataxia 2 (SCA2) even before the onset of the disease, but there is no information regarding its progression to the final stage of SCA2. In order to study the progression patterns of nerve conduction abnormalities in SCA2 we performed a prospective follow up evaluation of sensory and motor conduction in 21 SCA2 mutation carriers-initially presymptomatics- and 19 non-SCA2 mutation carriers during 20 years. The earliest electrophysiological alterations were the reduction of sensory amplitudes in median and sural nerves, which could be found 8 to 5 years prior disease onset and in the last 4 years of the preclinical stage respectively. These abnormalities were followed by the increase of sensory latencies and decrease of conduction velocities. Sensory amplitudes progressively decreased during the follow-up clinical stage, rendering almost all patients with abnormal amplitudes and lack of sensory potentials, with faster progression rates in patients with larger CAG repeat lengths. Peripheral motor nerves showed the later involvement. These findings were used to define three distinct stages that describe the progression of the peripheral neuropathy. We suggest that sensory amplitudes could be useful biomarkers to assess the progression of peripheral nerve involvement and therefore to evaluate future clinical trials of therapeutic agents(AU)
Asunto(s)
Humanos , Masculino , Femenino , Niño , Adolescente , Adulto , Persona de Mediana Edad , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Ataxias Espinocerebelosas/diagnóstico , Ataxias Espinocerebelosas/fisiopatologíaRESUMEN
Nerve conduction is profoundly affected in Spinocerebellar ataxia 2 (SCA2) even before the onset of the disease, but there is no information regarding its progression to the final stage of SCA2. In order to study the progression patterns of nerve conduction abnormalities in SCA2 we performed a prospective follow up evaluation of sensory and motor conduction in 21 SCA2 mutation carriers-initially presymptomatics- and 19 non-SCA2 mutation carriers during 20years. The earliest electrophysiological alterations were the reduction of sensory amplitudes in median and sural nerves, which could be found 8 to 5years prior disease onset and in the last 4years of the preclinical stage respectively. These abnormalities were followed by the increase of sensory latencies and decrease of conduction velocities. Sensory amplitudes progressively decreased during the follow-up clinical stage, rendering almost all patients with abnormal amplitudes and lack of sensory potentials, with faster progression rates in patients with larger CAG repeat lengths. Peripheral motor nerves showed the later involvement. These findings were used to define three distinct stages that describe the progression of the peripheral neuropathy. We suggest that sensory amplitudes could be useful biomarkers to assess the progression of peripheral nerve involvement and therefore to evaluate future clinical trials of therapeutic agents.
Asunto(s)
Enfermedades del Sistema Nervioso Periférico/diagnóstico , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Ataxias Espinocerebelosas/diagnóstico , Ataxias Espinocerebelosas/fisiopatología , Adolescente , Adulto , Ataxinas , Biomarcadores/análisis , Niño , Estudios de Cohortes , Progresión de la Enfermedad , Electrodiagnóstico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Nervio Mediano/metabolismo , Nervio Mediano/fisiopatología , Persona de Mediana Edad , Proteínas del Tejido Nervioso/genética , Conducción Nerviosa/genética , Enfermedades del Sistema Nervioso Periférico/genética , Valor Predictivo de las Pruebas , Estudios Prospectivos , Tiempo de Reacción/genética , Sensibilidad y Especificidad , Células Receptoras Sensoriales/fisiología , Índice de Severidad de la Enfermedad , Ataxias Espinocerebelosas/genética , Nervio Sural/metabolismo , Nervio Sural/fisiopatología , Factores de TiempoRESUMEN
Motor deficits are a critical component of the clinical characteristics of patients with spinocerebellar ataxiatype 2. However, there is no current information on the preclinical manifestation of those motor deficits in presymptomaticgene carriers. To further understand and characterize the onset of the clinical manifestation in this disease, we testedpresymptomatic spinocerebellar ataxia type 2 gene carriers, and volunteers, in a task that evaluates their motorperformance and their motor learning capabilities. Findings: 28 presymptomatic spinocerebellar ataxia type 2 gene carriers and an equal number of controlvolunteers matched for age and gender participated in the study. Both groups were tested in a prism adaptation taskknown to be sensible to both motor performance and visuomotor learning deficits. Our results clearly show that althoughmotor learning capabilities are intact, motor performance deficits are present even years before the clinical manifestation ofthe disease start.The results show a clear deficit in motor performance that can be detected years before the clinical onset ofthe disease. This motor performance deficit appears before any motor learning or clinical manifestations of the disease.These observations identify the performance coefficient as an objective and quantitative physiological biomarker that couldbe useful to assess the efficiency of different therapeutic agents...(AU)
Asunto(s)
Humanos , Ataxias Espinocerebelosas , Ataxias Espinocerebelosas/genéticaRESUMEN
BACKGROUND: Motor deficits are a critical component of the clinical characteristics of patients with spinocerebellar ataxia type 2. However, there is no current information on the preclinical manifestation of those motor deficits in presymptomatic gene carriers. To further understand and characterize the onset of the clinical manifestation in this disease, we tested presymptomatic spinocerebellar ataxia type 2 gene carriers, and volunteers, in a task that evaluates their motor performance and their motor learning capabilities. METHODS AND FINDINGS: 28 presymptomatic spinocerebellar ataxia type 2 gene carriers and an equal number of control volunteers matched for age and gender participated in the study. Both groups were tested in a prism adaptation task known to be sensible to both motor performance and visuomotor learning deficits. Our results clearly show that although motor learning capabilities are intact, motor performance deficits are present even years before the clinical manifestation of the disease start. CONCLUSIONS: The results show a clear deficit in motor performance that can be detected years before the clinical onset of the disease. This motor performance deficit appears before any motor learning or clinical manifestations of the disease. These observations identify the performance coefficient as an objective and quantitative physiological biomarker that could be useful to assess the efficiency of different therapeutic agents(AU)
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Proteínas del Tejido Nervioso/genética , Ataxias Espinocerebelosas/genética , Ataxias Espinocerebelosas/fisiopatología , Repeticiones de Minisatélite , Destreza Motora/fisiología , Ataxias Espinocerebelosas/etiología , Factores de Tiempo , Expansión de Repetición de TrinucleótidoRESUMEN
BACKGROUND: Motor deficits are a critical component of the clinical characteristics of patients with spinocerebellar ataxia type 2. However, there is no current information on the preclinical manifestation of those motor deficits in presymptomatic gene carriers. To further understand and characterize the onset of the clinical manifestation in this disease, we tested presymptomatic spinocerebellar ataxia type 2 gene carriers, and volunteers, in a task that evaluates their motor performance and their motor learning capabilities. METHODS AND FINDINGS: 28 presymptomatic spinocerebellar ataxia type 2 gene carriers and an equal number of control volunteers matched for age and gender participated in the study. Both groups were tested in a prism adaptation task known to be sensible to both motor performance and visuomotor learning deficits. Our results clearly show that although motor learning capabilities are intact, motor performance deficits are present even years before the clinical manifestation of the disease start. CONCLUSIONS: The results show a clear deficit in motor performance that can be detected years before the clinical onset of the disease. This motor performance deficit appears before any motor learning or clinical manifestations of the disease. These observations identify the performance coefficient as an objective and quantitative physiological biomarker that could be useful to assess the efficiency of different therapeutic agents.
Asunto(s)
Proteínas del Tejido Nervioso/genética , Ataxias Espinocerebelosas/genética , Ataxias Espinocerebelosas/fisiopatología , Adulto , Edad de Inicio , Ataxinas , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Repeticiones de Minisatélite , Destreza Motora/fisiología , Ataxias Espinocerebelosas/etiología , Factores de Tiempo , Expansión de Repetición de TrinucleótidoRESUMEN
Motor deficits are a critical component of the clinical characteristics of patients with spinocerebellar ataxia type 2. However, there is no current information on the preclinical manifestation of those motor deficits in presymptomatic gene carriers. To further understand and characterize the onset of the clinical manifestation in this disease, we tested presymptomatic spinocerebellar ataxia type 2 gene carriers, and volunteers, in a task that evaluates their motor performance and their motor learning capabilities...(AU)
Asunto(s)
Humanos , Degeneraciones Espinocerebelosas/genética , AtaxiaRESUMEN
Patients with spinocerebellar ataxia type 2 (SCA2), develop severe pontine nuclei, inferior olives, and Purkinje cell degeneration. This form of autosomal dominant cerebellar ataxia is accompanied by progressive ataxia and dysarthria. Although the motor dysfunction is well characterized in these patients, nothing is known about their motor learning capabilities. Here we tested 43 SCA2 patients and their matched controls in prism adaptation, a kind of visuomotor learning task. Our results show that their pattern of brain damage does not entirely disrupt motor learning. Rather, patients had impaired adaptation decrement, but surprisingly a normal aftereffect. Moreover, the mutation degree could discriminate the degree of adaptation. This pattern could reflect the net contribution of two adaptive mechanisms: strategic control and spatial realignment. Accordingly, SCA2 patients show an impaired strategic control that affects the adaptation rate, but a normal spatial realignment measured through the aftereffect. Our results suggest that the neural areas subserving spatial realignment are spared in this form of spinocerebellar ataxia.