Body Mass Index Is Significantly Associated With Disease Severity in Spinocerebellar Ataxia Type 2 Patients.

BACKGROUND: Spinocerebellar ataxia type 2 is a progressive neurodegenerative disorder due to an unstable expansion of a CAG repeat in the ATXN2 gene. Although weight loss has been associated with disease progression in several neurodegenerative conditions, it has been barely assessed in patients with spinocerebellar ataxia type 2. OBJECTIVE: The objective of this study was to test whether body mass index is altered in patients with spinocerebellar ataxia type 2 with varying expansion sizes from early to late disease stages. METHODS: A cross-sectional case-control study was performed, which included 222 clinically and molecularly diagnosed patients and 214 sex- and age-matched healthy individuals. ATXN2 genotypes and sex were considered as risk factors. Clinical outcomes included the body mass index, age at onset, disease duration, Scale for the Assessment and Rating of Ataxia score, disease stage, dysphagia, and progression rate. Multiple linear regression models were generated. RESULTS: Body mass index was significantly decreased in male patients, but not in female patients, relative to control subjects. In addition to sex, body mass index was significantly associated with age at onset and progression rate. Conversely, body mass index, along with repeat length in ATXN2 expanded alleles and disease duration, was associated with Scale for the Assessment and Rating of Ataxia score. In addition, body mass index, along with the age at onset and the repeat length in ATXN2 normal and expanded alleles, has a significant influence on progression rate. CONCLUSIONS: Body mass index might be a useful biomarker of disease severity, particularly in male patients with spinocerebellar ataxia type 2 in the context of nutritional interventions or clinical trials assessing the efficacy of promising new drugs. © 2021 International Parkinson and Movement Disorder Society.

Testosterone Levels Are Decreased and Associated with Disease Duration in Male Spinocerebellar Ataxia Type 2 Patients.

Spinocerebellar ataxia type 2 (SCA2) is a progressive neurodegenerative disorder due to an unstable expansion of a CAG repeat in the ATXN2 gene. Despite clinical and experimental evidence indicating the relevance of the gonadotropic axis to the prognosis and therapeutics for several late-onset neurodegenerative disorders, its functioning and association with disease severity have not been previously explored in SCA2. To assess serum levels of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), and their clinical relevance in SCA2 patients. A case-control study involving 94 Cuban SCA2 patients and 101 gender- and age-matched healthy controls was conducted. Testosterone, LH, and FSH serum levels were determined by radioimmunoassay or immunoradiometric assay systems. Clinical outcomes included age at onset, disease duration, Scale for the Assessment and Rating of Ataxia (SARA) score, and progression rate. Univariate general linear models were generated. Testosterone, LH, and FSH serum levels were significantly reduced in male SCA2 patients relative to control individuals. On average, there was a 35% reduction in testosterone levels in male patients versus male control individuals. Testosterone levels were associated with disease duration (r = 0.383; p = 0.025) and age at onset (r = 0.414; p = 0.011) in male SCA2 patients, but no association was observed between testosterone and CAG expansion size, SARA score, or progression rate. Testosterone levels might be a biomarker of disease progression in male SCA2 patients. Further studies are needed to explore the effects of low testosterone levels on non-motor symptoms, and to assess the potential of testosterone replacement therapy in male SCA2 patients.

Hereditary Ataxias in Cuba: A Nationwide Epidemiological and Clinical Study in 1001 Patients.

The prevalence estimations of hereditary ataxias are biased since most epidemiological studies are confined to isolated geographical regions and few nationwide studies are available. The study aims to assess the prevalence, distribution, and neurological features of the Cuban population with hereditary ataxias. A nationwide epidemiological study of hereditary ataxias was conducted in Cuba between March 2017 and June 2018. Patients were scheduled at the Cuban ataxia research center, various hospitals, or at their homes. Demographic and clinical variables were obtained through standardized questionnaires and validated clinical tools. Overall, 1001 patients were diagnosed with hereditary ataxias for a nationwide prevalence of 8.91 cases/100.000 inhabitants. Spinocerebellar ataxia type 2 (SCA2) was the commonest subtype, with highest prevalences at Holguín province (47.86/100.000), and a broad dissemination in the whole country. Most of neurological features were common between all SCA cohorts, but the frequencies of some of them varied between distinct subtypes. Within the SCA2 cohort, significant influences of long mutation size and higher disease duration over the muscle atrophy and oculomotor disorders were observed. Besides, higher disease durations were associated with resting tremor and dysphagia, whereas shorter disease durations were associated with hyperreflexia. The spreading of SCA2 to whole country and the documented raising of its prevalence set the rationales for higher-scope medical care and research strategies, supported in collaborative research networks. The wide epidemiological, clinical, and genetic characterization of this founder SCA2 population identifies this homogeneous cohort as an attractive source for the development of future clinical-genetic and therapeutic researches.

Comorbilidades y gravedad clínica de la COVID-19: revisión sistemática y meta-análisis / Comorbidities and clinical severity of COVID-19: systematic review and meta-analysis

Introducción: La emergencia de la COVID-19 se ha convertido en un serio problema de salud a nivel mundial. La identificación de comorbilidades asociadas a la presentación clínica grave de la COVID-19, es de importancia para el adecuado abordaje terapéutico de los pacientes afectados. Objetivo: Evaluar el riesgo de COVID-19 con presentación clínica grave en pacientes con comorbilidades. Material y métodos: Se realizó una revisión sistemática y meta-análisis en bases de datos especializadas en busca de artículos publicados hasta el 20 de marzo de 2020, que aportaran información sobre la asociación entre la gravedad de la presentación clínica de la COVID-19 y comorbilidades. Se empleó la razón de probabilidades con un intervalo de confianza de 95 por ciento, y modelos de efectos fijos o aleatorios. Resultados: En el análisis fueron incluidos 13 estudios para un total de 99 817 pacientes. Se obtuvieron los efectos globales para la hipertensión arterial (RP: 4,05; IC 95 por ciento: 3,45-4,74), enfermedad cardiovascular (RP: 4,39; IC 95 por ciento: 3,29-5,87), Diabetes Mellitus (RP: 3,53; IC 95 por ciento: 2,79-4,47), hábito de fumar (RP: 2,87; IC 95 por ciento: 1,81-4,54), enfermedades respiratoria (RP: 2,73; IC 95 por ciento: 2,55-2,94), renal (RP: 5,60; IC 95 por ciento: 4,13-7,60) y hepática crónicas (RP: 1,98 (IC 95 por ciento: 1,08-3,64) e inmunodeficiencias (RP: 2,90; IC 95 por ciento: 2,06-4,09), en pacientes graves en comparación con pacientes no graves. Conclusiones: La enfermedad renal crónica, la enfermedad cardiovascular, la hipertensión arterial y la Diabetes Mellitus están entre las comorbilidades que mayor riesgo implican para una presentación clínica grave en pacientes con COVID-19, seguidas en importancia por las inmunodeficiencias, hábito de fumar, enfermedad respiratoria crónica y enfermedad hepática crónica(AU)

Introduction: The recent emergence of COVID-19 has become a serious global health problem. The identification of comorbidities associated with the clinical severity in COVID-19 patients is of paramount significance for the appropriate therapeutic approach of affected patients. Objective: To evaluate the risk of severe clinical presentation of COVID-19 in patients with comorbidities. Materials and methods: A systematic literature search and meta-analysis was conducted in specialized databases to obtain information from articles published until March 20, 2020. All relevant papers with information on the association between clinical severity and comorbidities were included. The odds ratio with 95 percent confidence interval and fixed or random effect models were used. Results: Thirteen studies were included for a total of 99 817 patients. Global effects were obtained for hypertension (OR: 4.05; 95 percent CI: 3.45-4.74), cardiovascular disease (OR: 4.39; 95 percent CI: 3.29-5.87), diabetes mellitus (OR: 3.53; 95 percent CI: 2.79-4.47), smoking (OR: 2.87; 95 percent CI: 1.81-4.54), chronic lung disease (OR: 2.73; 95 percent CI: 2.55-2.94), chronic kidney disease (OR: 5.60; 95 percent CI: 4.13-7.60), chronic liver disease (OR: 1.98; 95 percent CI: 1.08-3.64), and immunodeficiency (OR: 2.90; 95 percent CI: 2.06-4.09) in severe patients compared with non-severe patients. Conclusions: Chronic kidney disease, cardiovascular disease, hypertension and diabetes are among the comorbidities with the highest risk of severe clinical presentation in COVID-19 patients, followed in importance by immunodeficiency, smoking, chronic lung disease and chronic liver disease(AU)

Relevancia de componentes del eje hipotálamo-hipófisis-gonadal en la fisiopatología de proteinopatías del sistema nervioso / Relevance of components of the hypothalamic-pituitary-gonadal axis in the pathophysiology of proteinopathies of the nervous system

RESUMEN Introducción: Varias proteinopatías del sistema nervioso están asociadas a la ocurrencia de alteraciones en componentes del eje hipotálamo-hipófisis-gonadal. Objetivo: Reflejar la relevancia de componentes del eje hipotálamo-hipófisis-gonadal en la fisiopatología de proteinopatías del sistema nervioso. Material y Métodos: Se realizó una revisión bibliográfica durante los meses de enero de 2018 a diciembre de 2018. Fueron consultadas bases de datos de referencia, con el uso de descriptores y operadores booleanos. La estrategia de búsqueda avanzada para la selección de los artículos fue empleada, teniendo en cuenta la calidad metodológica o validez de los estudios. Desarrollo: Fueron identificaron alteraciones del funcionamiento normal del eje hipotálamo-hipófisis-gonadal en varias proteinopatías del sistema nervioso. Las alteraciones más frecuentemente reportadas fueron el incremento en los niveles de gonadotropinas, principalmente de la hormona luteinizante, en la enfermedad de Alzheimer, y la disminución de los niveles de testosterona en las enfermedades de Alzheimer, Parkinson, Huntington y Esclerosis Lateral Amiotrófica, con el consiguiente agravamiento del fenotipo clínico. Se obtuvieron evidencias de naturaleza preliminar, que fundamentan la posible ocurrencia de disfunción hipotalámica en pacientes con ataxias espinocerebelosas. Conclusiones: Aun cuando existen evidencias que demuestran la existencia de un vínculo entre la fisiopatología de proteinopatías del sistema nervioso y alteraciones en componentes del eje hipotálamo-hipófisis-gonadal, se requerirán estudios más extensos e integrales para confirmar estas asociaciones y para caracterizar los mecanismos moleculares implicados.

ABSTRACT Introduction: Several proteinopathies of the nervous system are associated with disturbances in components of the hypothalamic-pituitary-gonadal axis. Objective: To assess the relevance of components of the hypothalamic-pituitary-gonadal axis in the pathophysiology of proteinopathies of the nervous system. Material and Methods: A literature review was carried out from January to December 2018. Several databases were searched by using descriptors and Boolean operators. Advanced search strategy was used for the selection of articles, taking into account the methodological quality and validity of the studies. Results: Disturbances of the normal function of the hypothalamic-pituitary-gonadal axis were identified in proteinopathies of the nervous system. The most frequently reported disturbances were the increase in gonadotropin levels, mainly in luteinizing hormone in Alzheimer´s disease, and the decrease in testosterone levels in Alzheimer´s, Parkinson´s and Huntington´s diseases, and Amyotrophic Lateral Sclerosis, with the resulting worsening of the clinical phenotype. Preliminary evidence was obtained, which was pointing to a possible hypothalamic dysfunction in Spinocerebellar ataxia patients. Conclusions: Even when evidences were gathered supporting a link between the pathophysiology of proteinopathies of the nervous system and disturbances in components of the hypothalamic-pituitary-gonadal axis, deeper and more comprehensive studies will be needed to confirm these associations and to characterize the underlying molecular mechanisms.

Aplicaciones de terapias de reemplazo celular al tratamiento de enfermedades poliglutamínicas / Applications of cell replacement therapies to the treatment of poly-glutamine diseases

Se realizó una revisión de la literatura especializada con el objetivo de evaluar el estado del arte en cuanto a la aplicación de terapias de reemplazo celular en enfermedades poliglutamínicas. Se consultaron las bases de datos HighWire y PubMed, con el uso de descriptores y operadores booleanos. Se recuperaron 84 artículos sobre la temática, publicados en revistas con un factor de impacto promedio de 5,42. Se discuten los estudios experimentales y pre-clínicos realizados con relación a terapias de reemplazo celular en enfermedades poliglutamínicas. Se demuestra la efectividad del uso de células madre de distintas fuentes en el mejoramiento de la función motora en modelos experimentales de enfermedades poliglutamínicas. Se revela la necesidad de realizar estudios multicéntricos a mediano y largo plazos, para la evaluación de los efectos terapéuticos de las terapias de reemplazo celular en enfermedades poliglutamínicas.

A review of the specialized literature was carried out with the aim of evaluating the state of the art regarding the application of cell replacement therapies in polyglutamine diseases. The HighWire and PubMed databases were consulted, with the use of Boolean descriptors and operators. 84 articles were retrieved on the subject, published in journals with an average impact factor of 5.42. The experimental and pre-clinical studies carried out in relation to cell replacement therapies in polyglutamine diseases are discussed. The effectiveness of the use of stem cells from different sources in the improvement of motor function in experimental models of polyglutamine diseases is demonstrated. The need to perform multicenter studies in the medium and long term is revealed, for the evaluation of the therapeutic effects of cell replacement therapies in polyglutamine diseases.

Neurorehabilitation therapy in spinocerebellar ataxia type 2: A 24-week, rater-blinded, randomized, controlled trial.

BACKGROUND: Neurorehabilitation has become in a widely used approach in spinocerebellar ataxias, but there are scarce powerful clinical studies supporting this notion. OBJECTIVE: The objective of this study was to assess the efficacy of a 24-week neurorehabilitative treatment in spinocerebellar ataxia type 2 patients. METHODS: A total of 38 spinocerebellar ataxia type 2 patients were enrolled in a rater-blinded, 1:1 randomized, controlled trial using neurorehabilitation for 24 weeks. The treated group received 6 hours of neurorehabilitation therapy, emphasizing on balance, coordination, and muscle strengthening on weekdays, whereas the control group did not receive this intervention. Primary outcome measure was the Scale for the Assessment and Rating of Ataxia score, whereas secondary outcome measures included the count of Inventory of Non-Ataxia Symptoms and saccadic eye movement variables. RESULTS: The rehabilitated group had high levels of adherence and retention to the therapy and showed a significant decrease of Scale for the Assessment and Rating of Ataxia score at 24 weeks when compared with the controls, mainly for the gait, stance, sitting, finger chase, and heel-shin test items. Changes in Scale for the Assessment and Rating of Ataxia scores were inversely correlated with the mutation size in the rehabilitated group. The nonataxia symptom count and saccadic measures were unchanged during the study. CONCLUSIONS: A comprehensive 24-week rehabilitation program significantly improves the motor cerebellar symptoms of spinocerebellar ataxia type 2 patients as assessed by the ataxia rating score likely as result of the partial preservation of motor learning and neural plasticity mechanisms. These findings provide evidence in support of this therapeutic approach as palliative treatment in spinocerebellar ataxia type 2 suggesting its use in combination with other symptomatic or neuroprotective drugs and in prodromal stages. © 2018 International Parkinson and Movement Disorder Society.

Spinocerebellar Ataxia Type 2 Is Associated with the Extracellular Loss of Superoxide Dismutase but Not Catalase Activity.

BACKGROUND: Spinocerebellar ataxia type 2 (SCA2) is an inherited and still incurable neurodegenerative disorder. Evidence suggests that pro-oxidant agents as well as factors involved in antioxidant cellular defenses are part of SCA2 physiopathology. AIM: To assess the influence of superoxide dismutase (SOD3) and catalase (CAT) enzymatic activities on the SCA2 syndrome. METHOD: Clinical, molecular, and electrophysiological variables, as well as SOD3 and CAT enzymatic activities were evaluated in 97 SCA2 patients and in 64 age- and sex-matched control individuals. RESULTS: Spinocerebellar ataxia type 2 patients had significantly lower SOD3 enzymatic activity than the control group. However, there were no differences between patients and controls for CAT enzymatic activity. The effect size for the loss of patients' SOD3 enzymatic activity was 0.342, corresponding to a moderate effect. SOD3 and CAT enzymatic activities were not associated with the CAG repeat number at the ATXN2 gene. SOD3 and CAT enzymatic activities did not show significant associations with the age at onset, severity score, or the studied electrophysiological markers. CONCLUSION: There is a reduced SOD3 enzymatic activity in SCA2 patients with no repercussion on the clinical phenotype.

Epidemiological, clinical, and molecular characterization of Cuban families with spinocerebellar ataxia type 3/Machado-Joseph disease.

BACKGROUND: Spinocerebellar Ataxia Type 3/Machado-Joseph Disease (SCA3/MJD) is a hereditary neurodegenerative disorder resulting from the expansion of CAG repeats in the ATXN3 gene. It is the most common autosomal dominant ataxia in the world, but its frequency prevalence in Cuba remains uncertain. We undertook a national study in order to characterize the ATXN3 gene and to determine the prevalence of SCA3/MJD in Cuba. RESULTS: Twenty-two individuals belonging to 8 non-related families were identified as carriers of an expanded ATXN3 allele. The affected families come from the central and western region of the country. Ataxia of gait was the initial symptom in all of the cases. The normal alleles ranged between 14 and 33 CAG repeats while the expanded ones ranged from 63 to 77 repeats. The mean age at onset was 40 ± 9 years and significantly correlated with the number of CAG repeats in the expanded alleles. CONCLUSIONS: This disorder was identified as the second most common form of spinocerebellar ataxia (SCA) in Cuba based on molecular testing, and showing a different geographical distribution from that of SCA2. This research constitutes the first clinical and molecular characterization of Cuban SCA3 families, opening the way for the implementation of predictive diagnosis for at risk family members.

SCA2 predictive testing in Cuba: challenging concepts and protocol evolution.

Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease caused by a CAG repeat expansion in the ATXN2 gene. Cuba has the highest prevalence (6.57 cases/10(5) inhabitants) of SCA2 in the world. The existence of 753 affected individuals and 7173 relatives at risk prompted the development in 2001 of the first predictive testing program in the country. The medical records of over 1193 individuals, who requested the test within a 13-year period, were analyzed retrospectively. The presymptomatic and the prenatal tests had uptake rates of 43.4 and 23.9 %, respectively. Several ethical challenges resulted from this program. These include the following: (1) withdrawal due to the initial protocol's length; (2) the request to participate by 16 at-risk adolescents; (3) the decision made by ten out of 33 couples with a test-positive fetus to carry the pregnancy to term, leading to de facto predictive testing of minors; (4) the elevated frequency of the ATXN2 gene large normal alleles (≥23 to 31 repeats) in the reference population. These issues have led to major changes in the guidelines of the predictive testing protocol: (1) the protocol length was shortened; (2) the inclusion criteria were expanded to reach at-risk adolescents with an interest in prenatal diagnosis; (3) interdisciplinary follow-up was offered to families in which test-positive fetuses were not aborted; (4) prenatal testing was made available to carriers of large normal alleles with ≥27 CAG repeats. The profiles of the participants were similar to those reported for other predictive testing programs for conditions like Huntington disease and familial adenomatous polyposis. The genetic counseling practices at the community level, the ample health education provided to the at-risk population, together with multidisciplinary and specialized attention to the affected families, are lessons from the Cuban experience that can be relevant for other international teams conducting predictive testing for other late-onset neurodegenerative disorders.

Strategy use, planning, and rule acquisition deficits in spinocerebellar ataxia type 2 patients.

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.

Evaluación del efecto del Compvit-B sobre la neuropatía periférica en pacientes con SCA2 en estadio ligero de la enfermedad / Evaluation of the effect of Compvit-B on peripheral neuropathy in patients with mild SCA2

INTRODUCCIÓN: la Ataxia Espinocerebelosa tipo 2 (SCA2) es una enfermedad neurodegenerativa severa que representa un serio problema de salud en Cuba, debido a las altas tasas de prevalencia e incidencia y a la ausencia de tratamientos curativos. OBJETIVOS: evaluar el efecto y la seguridad del tratamiento con altas dosis de vitaminas del complejo B (Compvit-B) sobre la neuropatía periférica en pacientes con SCA2. MÉTODOS: se realizó una investigación prospectiva de intervención clínica en 20 enfermos en estadio ligero los que se sometieron a un protocolo terapéutico mediante la administración intramuscular del COMPVIT B por 12 semanas. Durante las primeras 4 semanas los individuos recibieron dos bulbos semanales y a partir de la 5tasemana un solo bulbo. Inmediatamente antes y después del tratamiento los pacientes fueron evaluados mediantes exámenes clínicos y electrofisiológicos. RESULTADOS: una vez concluido el tratamiento, los pacientes mostraron un aumento significativo de las amplitudes de los potenciales de acción sensitivos de nervios mediano y sural, y en este último nervio se observó además reducción de la latencia y aumento de la velocidad de conducción. Los parámetros de la conducción nerviosa motora no se modificaron. Los potenciales evocados somatosensoriales de nervio mediano arrojaron una reducción significativa de la latencia del potencial de Erb. De manera interesante se observó una la disminución significativa de la frecuencia de aparición de las contracturas musculares dolorosas en el 53% de los casos después del tratamiento. Durante el estudio no se registraron eventos adversos. CONCLUSIONES: el presente estudio identifica una nueva opción terapéutica sintomática en la SCA2, brinda nuevas evidencias sobre las bases fisiopatológicas y el manejo clínico de las contracturas musculares dolorosas y justifican la realización de estudios más amplios en pacientes y portadores de la mutación, los que presentan tales manifestaciones muchos antes de debutar con la ataxia.

INTRODUCTION: Spinocerebellar ataxia type 2 (SCA2) is a severe neurodegenerative disease which constitutes a serious health problem in Cuba due to its high prevalence and incidence rates and the lack of curative treatments. OBJECTIVES: Evaluate the effect and safety of the treatment with high doses of B-complex vitamins (Compvit-B) on peripheral neuropathy in patients with SCA2. METHODS: A prospective clinical intervention study was conducted of 20 patients in the mild stage of the disease undergoing a therapeutic protocol consisting in intramuscular injection of Compvit-B for 12 weeks. Patients were administered two ampoules weekly in the first 4 weeks and one from the fifth week onwards. Immediately before and after the treatment patients underwent clinical and electrophysiological examination. RESULTS: Upon completion of the treatment patients showed a significant increase in the amplitude of the sensitive action potentials of the median and sural nerves. In the latter case there was also a decrease in latency and an increase in conduction velocity. Motor nerve conduction parameters were not modified. Somatosensory evoked potentials of the median nerve showed a significant reduction in the latency of Erb's potential. A significant decrease was also found in the frequency of painful muscle contractures in 53% of the cases after treatment. Adverse events were not recorded during the study. CONCLUSIONS: The study identifies a new therapeutic option for symptomatic SCA2, and provides new evidence of the pathophysiological bases and clinical management of painful muscle contractures. Broader studies should be conducted with patients and carriers of the mutation, who typically present such manifestations long before developing ataxia.

Evaluación preliminar del efecto del Compvit-B sobre procesos de memoria y aprendizaje en pacientes con SCA2 / Preliminary evaluation of the effect of Compvit-B on memory and learning processes in patients with SCA2

INTRODUCCIÓN: la ataxia Espinocerebelosa tipo 2 (SCA2) es una enfermedad neurodegenerativa que alcanza las mayores tasas de prevalencia e incidencia en Holguín, Cuba. Una de las principales manifestaciones clínicas de estos pacientes son los trastornos cognitivos, expresados fundamentalmente como déficits frontoejecutivos y de la memoria. OBJETIVO: evaluar el efecto del tratamiento con vitaminas del Complejo B sobre las funciones cognitivas, en pacientes cubanos con SCA2. MÉTODOS: se incluyeron 20 pacientes en una investigación de intervención clínica, empleando COMPVIT-B, durante 3 meses. Se evaluaron parámetros clínicos, como la escala SARA y cognitivos como el test de Stroop, el test de Fluencia verbal fonológica y el test de memoria verbal. Todos los estudios se realizaron antes y después del tratamiento. RESULTADOS: el estudio de las funciones frontoejecutivas reveló un aumento significativo del número de palabras mencionadas en el test de fluencia verbal fonológica, al terminar el estudio. Sin embargo, el test de Stroop no mostró cambios significativos. En relación al test de memoria verbal, se obtuvo un aumento del número de palabras recordadas en el primer ensayo, así como reducción del número de ensayos requeridos para recordar todas las palabras. La puntuación de la escala SARA no cambió significativamente. CONCLUSIONES: el presente trabajo constituye una evidencia adicional en favor del uso terapéutico y neuroprotector de las vitaminas del complejo B e identifica una nueva opción de tratamiento sintomatológico para los enfermos con SCA2, lo que incide positivamente en el mejoramiento de la calidad de vida de estos pacientes.

INTRODUCTION: Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease with the highest prevalence and incidence rates in the province of Holguín, Cuba. One of its main clinical manifestations is cognitive disorders, fundamentally expressed as frontal-executive and memory deficits. OBJECTIVE: Evaluate the effect of B-complex vitamins on cognitive functions in Cuban patients with SCA2. METHODS: Twenty patients were included in a clinical intervention study based on the use of Compvit-B for 3 months. An evaluation was conducted of clinical parameters such as the Scale for the Assessment and Rating of Ataxia (SARA), and cognitive parameters like the Stroop test, the phonological verbal fluency test and the verbal memory test. All the studies were conducted before and after the treatment. RESULTS: The study of frontal-executive functions revealed a significant increase in the number of words mentioned in the phonological verbal fluency test at the end of the study. However, the Stroop test did not show any significant change. The verbal memory test showed an increase in the number of words recalled in the first assay, and a reduction in the number of assays required to recall all the words. Scores on the SARA did not change significantly. CONCLUSIONS: The paper provides additional evidence in support of the therapeutic and neuroprotective use of B-complex vitamins and presents a new option of symptomatic treatment for patients with SCA2, which will lead to an improvement in their quality of life.

Progression of early features of spinocerebellar ataxia type 2 in individuals at risk: a longitudinal study.

BACKGROUND: The effects of ATXN2 expansion on the nervous system arise before the cerebellar syndrome can be diagnosed; however, progression of the underlying early clinical manifestations is unknown. We aimed to assess progression of the main clinical features in early stages of the spinocerebellar ataxia type 2 (SCA2). METHODS: We did this longitudinal study between Aug 12, 1986, and Sept 3, 2013, in carriers and non-carriers of the SCA2 mutation. We enrolled participants aged 6-60 years who were asymptomatic offspring or siblings of patients with SCA2. Participants were repeatedly assessed (two to seven times) until they presented definite cerebellar syndrome. All participants underwent standardised neurological examinations and electrophysiological (nerve conduction tests and somatosensory evoked potentials) and genetic assessments. FINDINGS: We enrolled 40 (73%) of 55 eligible participants to the baseline assessment, of whom 21 (13 women and eight men) were carriers of the SCA2 mutation, and 19 (14 women and five men) were non-carriers. Muscle cramps and sensory abnormalities were the most common clinical features in carriers (n=17 [81%] for both features) compared with controls (n=3 [16%] and n=4 [21%], respectively; χ(2)=84·58; p<0.0001, and χ(2)=72·03; p<0·0001, respectively) Both features showed a notable worsening over time and, in 17 (81%) carriers, age at onset was inversely correlated to CAG repeats (cramps: r -0·76, p=0·0004; sensory abnormalities: r -0·77, p=0·0004). Hyper-reflexia was associated with long time to ataxia onset (mean 5·71 years [SD 5·03]), whereas hyporeflexia was associated with short time (median 1·29 years [range 1-3]). Electrophysiological recordings obtained between 5 and 8 years before ataxia in 11 (52%) carriers showed reduced sensory amplitudes for median nerve (10·34 uV [SD 5·07]) and prolonged mean P40 latency (39·31 ms [2·40]) compared with age-matched and sex-matched controls (20·72 uV [9·08 uV]; p=0·0085, and 35·60 ms [2·05]; p=0·0023, respectively). INTERPRETATION: Early features of SCA2 are detectable before the onset of the cerebellar syndrome, and are associated with expanded CAG repeats and the time to onset of cerebellar syndrome. These findings could aid early diagnosis and genetic counselling, and also offer physiopathological insights that could help in the implementation of clinical trials in early stages of the disease. FUNDING: Cuban Ministry of Public Health.

Rol del eje tirotrópico en enfermedades neurodegenerativas / Thyrotropic Axis Role in Neurodegenerative Disorders

Las hormonas tiroideas actúan como reguladores primarios del metabolismo intermediario en todos los tejidos del organismo; tienen funciones de gran trascendencia a nivel del sistema nervioso, donde ejercen acciones potencialmente neuroprotectoras. Los niveles de las hormonas tiroideas están sujetos a una estrecha regulación en el sistema nervioso y se sugiere que incluso ligeras desviaciones del rango de normalidad pueden estar asociadas a enfermedades neurodegenerativas. En esta revisión se resumieron los hallazgos existentes en torno al papel de las hormonas tiroideas en la fisiología normal y patológica del sistema nervioso, con énfasis en enfermedades neurodegenerativas y los mecanismos moleculares implicados. Las evidencias indican un rol significativo para las hormonas tiroideas en varias enfermedades neurodegenerativas, si bien es necesaria la realización de estudios prospectivos de mayor envergadura para precisar su función y evaluar su utilidad como bio-marcadores y dianas terapéuticas.

Thyroid hormones are primary regulators of intermediate metabolism in all body tissues. Particularly, they have very important functions at the level of nervous system, even having potentially neuro-protective effects. Usually, thyroid hormone levels are under a very close regulation in the nervous system and, because of that, small deviations from the normality range can be associated to neurodegenerative conditions. In this review, evidences about the roles of thyroid hormones in normal and pathological physiology of the nervous system are summarized, with an emphasis in neurodegenerative disorders and the molecular mechanisms involved. Findings suggest a significant role for thyroid hormones in several neurodegenerative diseases, although larger prospective studies are needed to clarify their function and to assess their usefulness as biomarkers and therapeutic targets.

Actualización en enfermedad de Parkinson idiopática / Update on Idiopathic Parkinson’s disease

Se realizó una revisión general del estado actual de conocimiento de la enfermedad de Parkinson idiopática, se incluyeron aspectos etiopatogénicos, clínicos, de metodología diagnóstica y opciones terapéuticas. El diagnóstico de la enfermedad de Parkinson es uno de los retos actuales en el campo neurológico. En los últimos años se han producido avances significativos, fundamentalmente en el campo de la neuroimagen, que abren nuevas rutas en la investigación y sirven al médico como apoyo diagnóstico. A pesar de ello, es un proceso clínico que se cuestiona en cada momento.

A review on the current knowledge of idiopathic Parkinson's disease was carried out. Etiopathogenic, clinical, diagnostic methods and treatment options were included. The diagnosis of Parkinson's disease is one of the current challenges in the neurological field. In recent years significant progress has been made, mainly in the field of neuroimaging, which open new routes in scientific investfgation and medical diagnostic support. Nonetheless, it is a clinical process at issue in every moment.

Couples at risk for spinocerebellar ataxia type 2: the Cuban prenatal diagnosis experience.

Cuba reports the highest worldwide prevalence of spinocerebellar ataxia type 2 (SCA2) and the greatest number of descendants at risk. A protocol for genetic counseling, presymptomatic testing, and prenatal diagnosis of hereditary ataxias has been under development since 2001. Considering that the revision of the experience with prenatal diagnosis for SCA2 in Cuba would enable comparison of ours with international findings, we designed a descriptive study, based on the retrospective revision of the medical records belonging to the 58 couples that requested their inclusion in the program, during an 11-year period (2001-2011). Most of the participants in the prenatal diagnosis program were known presymptomatic carriers, diagnosed through the presymptomatic testing in the same period of study, for an uptake among them of 22.87 % (51 out of 223). In 28 cases, the fetuses were carriers, 20 of these couples (71.43 %) decided to terminate the pregnancy; the rest continued the pregnancy to term, this resulting in a predictive test for their unborn children. A predominance of females as the at-risk progenitor was observed. Except for a slightly lower average age, the results attained in the Cuban SCA2 prenatal diagnosis program resulted similar to the ones reported for Huntington disease in other countries. It is necessary to have easy access to the Cuban program through its expansion to other genetic centers along the island. Future research is needed to evaluate the long-term impact of both the predictive testing in unborn children and the selection of other reproductive options by the at-risk couples.

Lisuride reduces involuntary periodic leg movements in spinocerebellar ataxia type 2 patients.

Periodic leg movements (PLMs) are a common sleep disorder in spinocerebellar ataxia type 2 (SCA2) being associated to higher disease severity and altered sleep patterns. To assess the efficacy and safety of lisuride for the treatment of PLMs in SCA2 patients, an open-label clinical trial was conducted in 12 SCA2 patients suffering from PLMs associated to other subjective sleep complaints. All subjects received 0.1 mg of oral lisuride daily for 4 weeks. Primary outcome measure was the change of PLMs index. Changes in the subjective sleep quality, other polysomnographical sleep parameters, Scale for the Assessment and Rating of Ataxia score, and saccadic velocity were assessed as secondary outcome parameters. Safety assessments included hemoglobin, hematocrit, cholesterol, creatinine, and TGP. A significant decrease in both the PLMs index and R stage latency were observed during the treatment, associated to subjective improvement of frequent awakenings, early insomnia, restless leg syndrome, and nocturnal limb paresthesias in most cases. Ataxia score and saccadic pathology were unchanged. No significantly adverse events were observed. Our study suggests the efficacy of dopamine agonist therapy in the treatment of PLMs in SCA2, improving various subjective sleep complaints. These findings serve to promote the adequate management of sleep-related disorders in SCA2, which could improve the life quality of the patients.

Caracterización integral de la ataxia espinocerebelosa 2 en Cuba y su aplicación en proyectos de intervención / Comprehensive characterization of spinocerebellar ataxia type 2 in Cuba and its application in intervention projects

Introducción Cuba es el país con mayores tasas de prevalencia e incidencia para las ataxias hereditarias, lo que constituye un problema de salud que motivó la creación del Centro para la Investigación y Rehabilitación de Ataxias Hereditarias en Holguín. Objetivos Describir los principales resultados, aportes científicos, estrategias de intervención e impactos que durante más de 10 años se han obtenido por el citado centro, como modelo para el abordaje integral de las ataxias hereditarias en Cuba. Fuente de datos Se realizó una revisión en las bases de datos Pubmed-Medline y Scopus, analizando todos los artículos relevantes, comprendidos en el periodo 1978-2011. Se utilizó el descriptor «ataxia espinocerebelar¼, de elevada especificidad y sensibilidad para el tema en análisis. Síntesis de los datos La prevalencia de la enfermedad se ha mantenido constante durante 40 años, extendiéndose a toda la isla. La mutación ataxia espinocerebelosa tipo 2 es responsable del 60 % de la variabilidad fenotípica mientras que el 40 % restante se debe a factores modificadores genéticos y/o ambientales. Se ha descrito la existencia de un daño oxidativo severo, disminución de neuroprotectores y oligoelementos. Los estudios neurofisiológicos permitieron definir etapas evolutivas desde estadios preclínicos de la enfermedad así como biomarcadores de progresión y daño genético. Estos resultados proiciaron el diseño y ejecución de varios ensayos clínicos controlados en busca de un protocolo de tratamiento contra la enfermedad. Adicionalmente se brinda un servicio de diagnostico prenatal y presintomático con un impacto positivo sobre las familias afectadas. Conclusiones Las investigaciones sobre la ataxia espinocerebelosa tipo 2 cubana, como problema de salud, han tenido un enfoque integral. Los nuevos descubrimientos sobre la patogenia, la identificación de biomarcadores, los ensayos clínicos, el diagnóstico prenatal y presintomático permitieron conformar un nuevo modelo cubano para el abordaje de las ataxias hereditarias y el estudio de otras enfermedades neurodegenerativas.

Introduction Cuba is one of the countries with high rates of prevalence and incidence of hereditary ataxias, which is a health problem that encouraged the foundation of the Center for Research and Rehabilitation of Hereditary Ataxias in Holguín province. Objectives To describe the main results, scientific achievements, intervention strategies and impacts of this institution for more than 10 years, as a sort of pattern to be followed to approach hereditary ataxias in Cuba in a more comprehensive way. Data source Pubmed-Medline and Scopus database were reviewed in which all the relevant articles published from 1978 to 2011 were analyzed. Spinocerebelar ataxia, highly specific and sensitive subject headings, were used for the topic under analysis. Data synthesis The prevalence of this disease has remained unchanged for 40 years, being extended to the whole island. Spinocerebelar ataxia type 2 mutation accounts for 60% of the phenotypical variability whereas the remaining 40% is caused by genetic and/or environmental modifying factors. Severe oxidative damage, reduction of neuroprotectors and of oligoelements have been described. The neurophysiological studies allowed defining evolutionary phases from the preclinical stagings as well as progression and genetic damage biomarkers. These results allowed designing several controlled clinical assays in search of one treatment protocol for the disease. Additionally, prenatal and pre-symptomatic diagnosis service is rendered, with positive impact on affected families. Conclusions The research studies on spinocerebelar ataxia type 2 in Cuba as a health problem have had comprehensive approach. The new breakthroughs on pathogeny, identification of biomarkers, clinical assays, prenatal and presymptomatic diagnosis allowed making a new Cuban model to approach hereditary ataxias and the study of other neurodegenerative diseases.