Curso optativo sobre ataxia espinocerebelosa tipo 2 en la Universidad de Ciencias Médicas de Holguín

Introducción: Recientemente inició la formación de profesionales en una nueva modalidad de Programas Técnico Superior de Ciclo Corto en la especialidad Neurofisiología Clínica, en la Universidad de Ciencias Médicas de Holguín, atendiendo a la alta incidencia de enfermedades neurológicas, como la ataxia espinocerebelosa tipo 2, que constituye un serio problema de salud en Cuba. Un programa de curso optativo que aborde esta temática, contribuye al conocimiento de esta enfermedad para su investigación y posibles tratamientos. Objetivo: Diseñar un programa de curso optativo sobre diagnóstico e intervención físico-terapéutica en la fase prodrómica de la ataxia espinocerebelosa tipo 2 para estudiantes de Neurofisiología Clínica Primer Año en la Facultad de Enfermería ¨Arides Estévez Sánchez¨ de Holguín. Método: Se realizó una investigación didáctica metodológica utilizando los métodos empíricos: observación; teóricos: histórico-lógico, estudio documental, dialéctico; análisis-síntesis e inducción-deducción. Resultados: Se propuso un programa para curso optativo basado en la búsqueda de información científica y métodos empíricos, el cual fue estructurado en cuatro temas, con carácter presencial y duración de 24 horas. Se presentaron los contenidos por temas, objetivos, conocimientos esenciales a adquirir, habilidades principales a dominar y sistema de evaluación. Conclusiones: La aplicación de este programa contribuye a desarrollar habilidades en los profesionales en formación, en el conocimiento de la fase prodrómica de esta enfermedad.

Introduction: It recently began the training of professionals in a new modality of Programas Técnico Superior de Ciclo Corto (Short Cycle Superior Technical Programs) in the Clinical Neurophysiology specialty, at the Universidad de Ciencias Médicas de Holguín, attending to the high incidence of neurological diseases, such as spinocerebellar ataxia type 2, which constitutes a serious health problem in Cuba. This is an elective course program that addresses this topic and contributes to the knowledge of this disease, in order to improve research and possible treatments. Objective: To design an elective course program on diagnosis and physical-therapeutic intervention in the prodromal phase of spinocerebellar ataxia type 2 for first year Clinical Neurophysiology students at the ¨Arides Estévez Sánchez¨ School of Nursing in Holguín. Method: A methodological didactic research was carried out using the empirical methods: observation; theoretical: historical-logical, documentary study, dialectical; analysis-synthesis and induction-deduction. Results: A program was proposed for an optional course, based on the search for scientific information and empirical methods, which was structured in four themes, in face-to-face modality and with a duration of 24 hours. The contents were presented by themes, objectives, essential knowledge to acquire, main skills to master and evaluation system. Conclusions: The application of this program contributes to developing skills in training professionals, in the knowledge of the prodromal phase of this disease.

Introdução: Iniciou-se recentemente a formação de profissionais em uma nova modalidade de Programas Técnicos Superiores de Ciclo Curto na especialidade de Neurofisiologia Clínica, na Universidad de Ciencias Médicas de Holguín, atendendo à alta incidência de doenças neurológicas, como a ataxia espinocerebelar tipo 2, que constitui um grave problema de saúde em Cuba. Um programa de disciplina eletiva que aborde esse tema contribui para o conhecimento dessa doença para sua investigação e possíveis tratamentos. Objetivo: Elaborar um programa de disciplina eletiva sobre diagnóstico e intervenção fisioterapêutica na fase prodrômica da ataxia espinocerebelar tipo 2 para alunos do primeiro ano de Neurofisiologia Clínica da Escola de Enfermagem ¨Arides Estévez Sánchez¨ de Holguín. Método: Foi realizada uma pesquisa didática metodológica utilizando os métodos empíricos: observação; teórico: histórico-lógico, estudo documental, dialético; análise-síntese e indução-dedução. Resultados: Foi proposto um programa para um curso opcional baseado na busca de informações científicas e métodos empíricos, o qual foi estruturado em quatro temas, com caráter presencial e duração de 24 horas. Os conteúdos foram apresentados por temas, objetivos, conhecimentos essenciais a adquirir, principais competências a dominar e sistema de avaliação. Conclusões: A aplicação deste programa contribui para o desenvolvimento de competências nos profissionais em formação, no conhecimento da fase prodrómica desta doença.

Weight loss is correlated with disease severity in Spinocerebellar ataxia type 2: a cross-sectional cohort study.

BACKGROUND: Body weight changes occur frequently during advanced stages of Spinocerebellar Ataxia type 2 (SCA2), nevertheless limited information exists on biomarkers of nutritional status of these patients. OBJECTIVE.: To assess changes in surrogate nutritional markers of SCA2 patients; to explore their associations with expanded CAG repeats and disease severity. METHODS: One-hundred-thirteen SCA2 patients and 50 healthy controls underwent a comprehensive anthropometrical and biochemical assessment protocol of the nutritional status. Neurological and genotype assessments were also performed. RESULTS: A decrease in weight, body mass index (BMI), cutaneous skinfold thickness, fat mass, arm muscle circumference, calf circumference and skeletal muscle mass was observed in SCA2 patients compared to the controls. The total/HDL cholesterol ratio was significantly reduced in patients. BMI was correlated with the age at onset. Overall, anthropometric measures were correlated with clinical markers of disease severity and were more evident in severe and moderate cases. CONCLUSIONS: Using anthropometric measures in the assessment of the nutritional status of SCA2 patients might provide hints about pathophysiological mechanisms that underlie metabolic abnormalities in SCA2. Anthropometric are close related with disease severity and progression, and trigger preventive therapies aimed to ameliorate weight loss and wasting in these patients.

Prodromal Spinocerebellar Ataxia Type 2 Subjects Have Quantifiable Gait and Postural Sway Deficits.

BACKGROUND: The search for valid preclinical biomarkers of cerebellar dysfunction is a key research goal for the upcoming era of early interventional approaches in spinocerebellar ataxias. This study aims to describe novel preclinical biomarkers of subtle gait and postural sway abnormalities in prodromal spinocerebellar ataxia type 2 (pre-SCA2). METHODS: Thirty pre-SCA2 patients and their matched healthy controls underwent quantitative assessments of gait and postural sway using a wearable sensor-based system and semiquantitative evaluation of cerebellar features by SARA (Scale for the Assessment and Rating of Ataxia) score. RESULTS: Quantitative analysis of natural gait showed a significantly larger variability of the swing period, toe-off angle and toe-out angle in pre-SCA2, and larger mean coronal and transverse ranges of motion of the trunk at the lumbar location and of the sagittal range of motion of the trunk at the sternum location compared to controls. During tandem gait, pre-SCA2 subjects showed larger lumbar, trunk, and arm ranges of motion than controls. Postural sway analysis showed excessive body oscillation that was increased in tandem stance. Overall, these abnormalities were detected in pre-SCA2 patients without clinical evidence of abnormalities in SARA. The toe-off angle and swing time variability were significantly correlated with the time to ataxia onset, whereas the toe-off angle and transverse range of motion at trunk position during tandem gait were significantly associated with the SARA score. CONCLUSIONS: This study demonstrates early alteration of gait and postural sway control in prodromal SCA2 using a wearable sensor-based system. This offers new pathophysiological hints into this early disease stage and provides novel potential biomarkers for future clinical trials. © 2020 International Parkinson and Movement Disorder Society.

Propuesta de asignatura Generalidades de la Estimulación Magnética Transcraneal para técnicos superiores de Neurofisiología Clínica / Course proposal Generalities of Transcranial Magnetic Stimulation for senior technicians of Clinical Neurophysiology

Introducción: Recientemente se inició la formación de profesionales en una nueva modalidad de Programas Técnico Superior de Ciclo Corto, en la especialidad de Neurofisiología Clínica. Esto responde a la necesidad de la formación de profesionales de la salud en el estudio de las enfermedades neurológicas. La estimulación magnética transcraneal constituye una herramienta importante en el diagnóstico y tratamiento de estas enfermedades. Sin embargo, se carece de un programa para la formación de los estudiantes en el estudio y aplicación de esta técnica. Objetivo: Diseñar un programa de curso propio sobre generalidades de la estimulación magnética transcraneal, para estudiantes de primer año de Neurofisiología Clínica. Métodos: Se realizó una investigación didáctica metodológica utilizando los métodos empíricos y teóricos observación, histórico lógico, estudio documental y bibliográfico, dialéctico, análisis y síntesis, inducción y deducción. Resultados: Se propuso un programa para curso propio que se estructuró en siete temas, con carácter presencial y duración de 32 horas. Se presentaron los contenidos por temas, objetivos, conocimientos esenciales a adquirir, habilidades principales a dominar y sistema de evaluación. Conclusiones: La aplicación de este programa contribuye al desarrollo de habilidades y el desempeño exitoso de los profesionales en formación, en el campo del conocimiento de la técnica de estimulación magnética transcraneal para el diagnóstico y tratamiento de las enfermedades neurológicas(AU)

Introduction: Recently began the training of professionals in a new modality of short-cycle Higher Technical Programs, in the specialty of Clinical Neurophysiology. This responds to the need of training health professionals in the study of neurological diseases, whose incidence rates have increased in recent years. Transcranial magnetic stimulation is an important tool in the diagnosis and treatment of these diseases. However, there is a lack of a program for the training of students in the study and application of this technique. Objective: Tto design an own course program on the generalities of transcranial magnetic stimulation, for first-year students of Clinical Neurophysiology. Method: A methodological didactic research was carried out using the empirical and theoretical methods, observation, logical historical, documentary and bibliographic study, dialectic, analysis and synthesis, induction and deduction. Results: A program for the course was proposed, structured in seven topics, with a face-to-face character and a duration of 32 hours. The contents were presented by topics, objectives, essential knowledge to acquire, main skills to master and an evaluation system. Conclusions: The application of this program contributes to the development of skills and the successful performance of professionals in training, in the field of knowledge of the transcranial magnetic stimulation technique for the diagnosis and treatment of neurological diseases(AU)

Introdução: Iniciou recentemente a formação de profissionais numa nova modalidade de Cursos Técnicos Superiores de Ciclo Curto, na especialidade de Neurofisiologia Clínica. Isso responde à necessidade de formação de profissionais de saúde no estudo das doenças neurológicas. A estimulação magnética transcraniana é uma ferramenta importante no diagnóstico e tratamento dessas doenças. No entanto, falta um programa de treinamento dos alunos no estudo e aplicação desta técnica. Objetivo: Desenhar um programa próprio sobre as generalidades da estimulação magnética transcraniana, para alunos do primeiro ano de Neurofisiologia Clínica. Método: Realizou-se uma investigação metodológica didática utilizando os métodos empírico e teórico de observação, histórico lógico, estudo documental e bibliográfico, dialética, análise e síntese, indução e dedução. Resultados: Foi proposto um programa de curso próprio, estruturado em sete temas, com caráter presencial e duração de 32 horas. Os conteúdos foram apresentados por tópicos, objetivos, conhecimentos essenciais a adquirir, competências principais a dominar e um sistema de avaliação. Conclusões: A aplicação deste programa contribui para o desenvolvimento de competências e o desempenho bem sucedido de profissionais em formação, no domínio do conhecimento da técnica de estimulação magnética transcraniana para o diagnóstico e tratamento de doenças neurológicas(AU)

Features of speech and swallowing dysfunction in pre-ataxic spinocerebellar ataxia type 2.

OBJECTIVE: To determine whether objective and quantitative assessment of dysarthria and dysphagia in spinocerebellar ataxia type 2 (SCA2), specifically at pre-ataxic and early disease phases, can act as sensitive disease markers. METHODS: Forty-six individuals (16 with pre-ataxic SCA2, 14 with early-stage ataxic SCA2, and 16 healthy controls) were recruited in Holguin, Cuba. All participants underwent a comprehensive battery of assessments including objective acoustic analysis, clinician-derived ratings of speech function and swallowing, and quality of life assessments of swallowing. RESULTS: Reduced speech agility manifest at the pre-ataxic stage was observed during diadochokinetic tasks, with the magnitude of speech deficit augmented in the early ataxic stage. Speech rate was slower in early-stage ataxic SCA2 compared with pre-ataxic SCA2 and healthy controls. Reduced speech agility and speech rate correlated with disease severity and time to ataxia onset, verifying that speech deficits occur prior to ataxia onset and increase in severity as the disease progresses. Whereas dysphagia was observed in both pre-ataxic and ataxic SCA2, it was not associated with swallowing-related quality of life, disease severity, or time to ataxia onset. CONCLUSIONS: Speech and swallowing deficits appear sensitive to disease progression in early-stage SCA2, with syllabic rate a viable marker. Findings provide insight into mechanisms of disease progression in early-stage SCA2, signaling an opportunity for stratifying early-stage SCA2 and identifying salient markers of disease onset as well as outcome measures in future early-stage therapeutic studies.

EMG Rectification Is Detrimental for Identifying Abnormalities in Corticomuscular and Intermuscular Coherence in Spinocerebellar Ataxia Type 2.

Corticomuscular and intermuscular coherence (CMC, IMC) reflect connectivity between neuronal activity in the motor cortex measured by electroencephalography (EEG) and muscular activity measured by electromyography (EMG), or between activity in different muscles, respectively. There is an ongoing debate on the appropriateness of EMG rectification prior to coherence estimation. This work examines the effects of EMG rectification in CMC and IMC estimation in 20 spinocerebellar ataxia type 2 (SCA2) patients, 16 prodromal SCA2 gene mutation carriers, and 26 healthy controls during a repetitive upper or lower limb motor task. Coherence estimations were performed using the non-rectified raw EMG signal vs. the rectified EMG signal. EMG rectification decreases the level of significance of lower beta-frequency band CMC and IMC values in SCA2 patients and prodromal SCA2 mutation carriers vs. healthy controls, and also results in overall lower coherence values. EMG rectification is detrimental for beta-frequency band CMC and IMC estimation. One likely reason for this effect is distortion of coherence estimation in high-frequency signals, where the level of amplitude cancelation is high.

Ataxias cerebelosas e infecciones virales: caracterización clínica y mecanismos neuropatogénicos / Cerebellar ataxias and viral infections: clinical characterization and neuropathogenic mechanisms

Introducción: La ataxia constituye una alteración en la coordinación de los movimientos, resultado de una disfunción del cerebelo, sus conexiones, así como alteraciones en la médula espinal, nervios periféricos o una combinación de estas condiciones. Las ataxias se clasifican en hereditarias, esporádicas y en adquiridas o secundarias, en las cuales los virus neurotrópicos constituyen los principales causantes. Objetivo: Actualizar los conocimientos relacionados con las ataxias causadas por virus neurotrópicos y los mecanismos neurodegenerativos que pudieran tener relación con la ataxia. Métodos: Se realizó una revisión bibliográfica incluyendo artículos publicados en las principales bases de datos bibliográficas (Web of Sciences, Scopus, SciELO). Se utilizaron las palabras claves: ataxia, virus neurotrópicos, ataxias cerebelosas, ataxias infecciosas, en inglés y español. Análisis e integración de la información: Los virus más conocidos que provocan ataxias infecciosas son el virus de inmunodeficiencia humana, virus del herpes simple, virus del herpes humano tipo 6, virus de la varicela zoster, virus Epstein-Barr, virus del Nilo Occidental, y enterovirus 71, aunque existen otros virus que causan esta afectación. Los mecanismos neuropatogénicos sugeridos son la invasión directa del virus y procesos inmunopatogénicos desencadenados por la infección. Estos virus pueden causar ataxia cerebelosa aguda, ataxia aguda posinfecciosa, síndrome opsoclono-mioclono-atáxico y ataxia por encefalomielitis aguda diseminada. Aunque la mayoría de los reportes de casos informan la evolución satisfactoria de los pacientes, algunos refieren complicaciones neurológicas e incluso la muerte. Conclusiones: Actualmente existe la necesidad de profundizar en el estudio de este tipo de ataxia para favorecer su diagnóstico y tratamiento(AU)

Introduction: Ataxia is an alteration in the coordination of movements caused by a dysfunction of the cerebellum and its connections, as well as alterations in the spinal cord, the peripheral nerves, or a combination of these factors. Ataxias are classified into hereditary, sporadic and acquired or secondary, in which neurotropic viruses are the main causative agents. Objective: Update knowledge about ataxias caused by neurotropic viruses and the neurodegenerative mechanisms which could bear a relationship to ataxia. Methods: A review was conducted of papers published in the main bibliographic databases (Web of Sciences, Scopus, SciELO), using the search terms ataxia, neurotropic virus, cerebellar ataxias, infectious ataxias, in English and in Spanish. Discussion: The best known viruses causing infectious ataxias are the human immunodeficiency virus, herpes simplex virus, human herpesvirus 6, varicella zoster virus, Epstein-Barr virus, Western Nile virus and enterovirus 71, though other viruses may also cause this condition. The neuropathogenic mechanisms suggested are direct invasion of the virus and immunopathogenic processes triggered by the infection. These viruses may cause acute cerebellar ataxia, acute postinfectious ataxia, opsoclonus-myoclonus-ataxia syndrome and ataxia due to acute encephalomyelitis disseminata. Though most case reports describe a satisfactory evolution of patients, some refer to neurological complications and even death. Conclusions: There is a current need to carry out further research about this type of ataxia to improve its diagnosis and treatment(AU)

Neurorehabilitation Improves the Motor Features in Prodromal SCA2: A Randomized, Controlled Trial.

BACKGROUND: The search for early interventions is a novel approach in spinocerebellar ataxias, but there are few studies supporting this notion. This article aimed to assess the efficacy of neurorehabilitation treatment in prodromal spinocerebellar ataxia type 2. METHODS: Thirty spinocerebellar ataxia type 2 preclinical carriers were enrolled in a randomized, controlled trial using neurorehabilitation. The intervention in the treated group was 4 hours per day, 5 days per week for 12 weeks, emphasizing static balance, gait, and limb coordination. The control group did not receive rehabilitation. The primary outcome measure was the time for 5-m tandem gait over the floor. Secondary outcomes included other timed tests with increased motor complexity, as well as the scores of the SARA and the Inventory of Non-ataxia Symptoms. RESULTS: The times for 5-m tandem gait over the floor and the mattress were significantly reduced only in the rehabilitated group. Moreover, the times upholding the tandem stance over a mattress and the seesaw were notably increased only in this group. Likewise, the finger-nose and the heel-shin tests were improved in the rehabilitated group alone. The SARA score and the count of nonataxia symptoms were unchanged. CONCLUSIONS: This rehabilitation program improves the subtle gait, postural and coordinative deficits in prodromal spinocerebellar ataxia type 2, which provided novel hints about the preservation of motor learning and neural plasticity mechanisms in early disease stages, leading chances for other interventional approaches in this and other spinocerebellar ataxias. © 2019 International Parkinson and Movement Disorder Society.

Insights into cognitive decline in spinocerebellar Ataxia type 2: a P300 event-related brain potential study.

BACKGROUND: Cognitive decline is a common non-motor feature characterizing Spinocerebellar Ataxia type 2 (SCA2) during the prodromal stage, nevertheless a reduced number of surrogate biomarkers of these alterations have been described. OBJECTIVE: To provide insights into cognitive dysfunction in SCA2 patients using P300 event-related potentials (ERP) and to evaluate these measures as biomarkers of the disease. METHODS: A cross-sectional study was performed with 30 SCA2 patients, 20 preclinical carriers and 33 healthy controls, who underwent visual, auditory P300 ERPs, and neurological examinations and ataxia scoring. RESULTS: SCA2 patients showed significant increase in P300 latencies and decrease of P300 amplitudes for visual and auditory stimuli, whereas preclinical carriers exhibit a less severe, but significant prolongation of P300 latencies. Multiple regression analyses disclosed a significant effect of SARA score on visual P300 abnormalities in patients as well as of the time to ataxia onset on visual P300 latencies in preclinical carriers. CONCLUSIONS: This paper demonstrated the role of P300 ERP for the study of attentional, discriminative and working memory abnormalities in SCA2 patients and for the search of surrogate biomarkers from prodromal to the symptomatic stages. Moreover, our findings provide psychophysiological evidences supporting the cerebellar involvement in cognitive processes and allows us to identify promising outcome measures for future trials focusing on cognitive dysfunction.

Progression of corticospinal tract dysfunction in pre-ataxic spinocerebellar ataxia type 2: A two-years follow-up TMS study.

OBJECTIVE: Corticospinal tract (CST) dysfunction is common in the pre-ataxic stage of spinocerebellar ataxia type 2 (SCA2) but quantitative assessment of its progression over time has not been explored. The aim of this study was to quantify the progression of CST dysfunction in pre-ataxic SCA2 using transcranial magnetic stimulation (TMS). METHODS: Thirty-three pre-ataxic SCA2 mutation carriers and a 33 age- and gender-matched healthy controls were tested at baseline and 2-years follow-up by standardized clinical exams, validated clinical scales, and TMS. RESULTS: Pre-ataxic SCA2 mutation carriers showed a significant increase of resting motor thresholds (RMT) to abductor pollicis brevis (APB) and tibialis anterior (TA) muscles, and of central motor conduction time (CMCT) to TA at 2-years follow-up, over and above changes in healthy controls. The changes in the pre-ataxic SCA2 mutation carriers were independent of the presence of clinical signs of CST dysfunction at baseline, and independent of conversion to clinically definite SCA2 at 2-years follow-up. CONCLUSIONS: TMS markers of CST dysfunction progress significantly during the pre-ataxic stage of SCA2. SIGNIFICANCE: TMS measures of CST dysfunction may provide biomarkers of disease progression prior to clinical disease expression that have potential utility for monitoring neuroprotective therapies in future clinical trials.

Early corticospinal tract damage in prodromal SCA2 revealed by EEG-EMG and EMG-EMG coherence.

OBJECTIVE: Clinical data suggest early involvement of the corticospinal tract (CST) in spinocerebellar ataxia type 2 (SCA2). Here we tested if early CST degeneration can be detected in prodromal SCA2 mutation carriers by electrophysiological markers of CST integrity. METHODS: CST integrity was tested in 15 prodromal SCA2 mutation carriers, 19 SCA2 patients and 25 age-matched healthy controls, using corticomuscular (EEG-EMG) and intermuscular (EMG-EMG) coherence measures in upper and lower limb muscles. RESULTS: Significant reductions of EEG-EMG and EMG-EMG coherences were observed in the SCA2 patients, and to a similar extent in the prodromal SCA2 mutation carriers. In prodromal SCA2, EEG-EMG and EMG-EMG coherences correlated with the predicted time to ataxia onset. CONCLUSIONS: Findings indicate early CST neurodegeneration in SCA2. EEG-EMG and EMG-EMG coherence may serve as biomarkers of early CST neurodegeneration in prodromal SCA2 mutation carriers. SIGNIFICANCE: Findings are important for developing preclinical disease markers in the context of currently emerging disease-modifying therapies of neurodegenerative disorders.

Corticomuscular Coherence: a Novel Tool to Assess the Pyramidal Tract Dysfunction in Spinocerebellar Ataxia Type 2.

Clinical signs of corticospinal tract dysfunction are a common feature of spinocerebellar ataxia type 2 (SCA2) patients. The objective of this study is to assess dysfunction of the corticospinal tract in SCA2 using corticomuscular coherence. Testing corticomuscular coherence and rating of ataxia severity and non-ataxia symptoms were performed in 19 SCA2 patients and 24 age-matched controls. Central motor conduction times (CMCT) to upper and lower right limbs were obtained for the SCA2 group using Transcraneal magnetic stimulation (TMS). SCA2 patients exhibited a significant reduction of corticomuscular coherence for lower limbs, but not for upper limbs. This difference remained significant, even when excluding those individuals with clinical signs of corticospinal tract dysfunction. Corticomuscular coherence for lower limbs correlated inversely with CMCT to tibialis anterior muscle. Corticomuscular coherence could be a valuable electrophysiological tool to assess the corticospinal tract involvement in SCA2, even in the absence of clinical signs of corticospinal tract dysfunction.

Abnormal corticospinal tract function and motor cortex excitability in non-ataxic SCA2 mutation carriers: A TMS study.

OBJECTIVE: To evaluate if the corticospinal tract is affected in the prodromal stage of spinocerebellar ataxia type 2 (SCA2), prior to development of the cerebellar syndrome. METHODS: A cross-sectional study was conducted in 37 non-ataxic SCA2 mutation carriers and in age- and sex-matched healthy controls. All subjects underwent clinical assessment and transcranial magnetic stimulation to determine corticospinal tract integrity to the right abductor pollicis brevis and tibialis anterior muscles. RESULTS: Non-ataxic SCA2 mutation carriers showed significantly higher resting and active motor thresholds for both muscles, and prolonged cortical silent periods and central motor conduction times (CMCT), compared to controls. CMCT to the tibialis anterior correlated directly with CAG repeat size, and inversely with predicted time to ataxia onset. CONCLUSION: Findings provide novel electrophysiological evidence for affection of the corticospinal tract and motor cortex in prodromal SCA2. Slowed conduction in the corticospinal tract to the lower limbs reflects polyglutamine neurotoxicity, and predicts time to ataxia onset. SIGNIFICANCE: Identification of corticospinal tract damage and decreases motor cortical excitability in the prodromal stage of SCA2 allows early disease monitoring. This will become important as soon as effective neuroprotective treatment will be available.