COVID-19 Impacts the Mental Health and Speech Function in Spinocerebellar Ataxia Type 2: Evidences from a Follow-Up Study.

Limited evidence suggests that the SARS-CoV-2 infection can accelerate the progression of neurodegenerative diseases, but this has been not verified in the spinocerebellar ataxias (SCA). The objective of this study is to assess the impact of COVID-19 on the mental health and motor features of SCA2. A follow-up study was carried out in 170 Cuban SCA2 subjects and 87 community controls between 2020 and 2021. All subjects underwent a structured questionnaire to assess the risks of exposure to COVID-19, the confirmation of COVID-19 diagnosis, and the Hospital Anxiety and Depression Scale (HADS). Moreover, 36 subjects underwent the Scale for the Assessment and Rating of ataxia (SARA). The risk of exposure to SARS-CoV-2 and the frequency of COVID-19 were similar between the ataxia cohort and the community controls. Within the ataxia group, significantly increased HADS scores existed at the 2nd visit in both groups, but this increase was more evident for the infected group regarding the depression score. Moreover, a significant within-group increase of SARA score was observed in the infected group but not the non-infected group, which was mainly mediated by the significant increase of the speech item score in the infected group. Similar results were observed within the subgroup of preclinical carriers. Our study identified no selective vulnerability nor protection to COVID-19 in SCA2, but once infected, the patients experienced a deterioration of mental health and speech function, even at preclinical disease stage. These findings set rationales for tele-health approaches that minimize the detrimental effect of COVID-19 on SCA2 progression and identify SCA2 individuals as clinical model to elucidate the link between SARS-CoV-2 infection and neurodegeneration.

Erythropoietin in Spinocerebellar Ataxia Type 2: Feasibility and Proof-of-Principle Issues from a Randomized Controlled Study.

BACKGROUND: Several pieces of evidence have shown the neurotrophic effect of erythropoietin (EPO) and its introduction in the therapeutic practice of neurological diseases. However, its usefulness in the treatment of spinocerebellar ataxia type 2 (SCA2) has not been proven despite the fact that it is endogenously reduced in these patients. OBJECTIVE: The study aims to investigate the safety, tolerability, and clinical effects of a nasally administered recombinant EPO in SCA2 patients. METHODS: Thirty-four patients were enrolled in this double-blind, randomized, placebo-controlled, phase I-II clinical trial of the nasally administered human-recombinant EPO (NeuroEPO) for 6 months. The primary outcome was the change in the spinocerebellar ataxia functional index (SCAFI), while other motor, neuropsychological, and oculomotor measures were assessed. RESULTS: The 6-month changes in SCAFI score were slightly higher in the patients allocated to NeuroEPO treatment than placebo in spite of the important placebo effect observed for this parameter. However, saccade latency was significantly decreased in the NeuroEPO group but not in placebo. The frequency and severity of adverse events were similar between both groups, without evidences of hematopoietic activity of the drug. CONCLUSIONS: This study demonstrated the safety and tolerability of NeuroEPO in SCA2 patients after 6 months of treatments and suggested a small clinical effect of this drug on motor and cognitive abnormalities, but confirmatory studies are warranted. © 2022 International Parkinson and Movement Disorder Society.

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.

Impacts of the COVID-19 Pandemic on the Mental Health and Motor Deficits in Cuban Patients with Cerebellar Ataxias.

Although there are no convincing evidences of detrimental effect of SARS-CoV2 infection on the cerebellum, the COVID-19 pandemic could impact the life quality of patients with cerebellar ataxias, but few studies have addressed this concern. To assess the motor and mental health changes caused by the COVID-19 pandemics in Cuban patients with cerebellar ataxias, three hundred four patients with cerebellar ataxias and 167 healthy controls were interviewed for risks of exposure to COVID-19, and the self-perception of the pandemics' impact on the disease progression and on the mental health. All subjects underwent the Hospital Anxiety and Depression Scale. The patients reported low exposition to SARS-CoV2 infection, but one case was confirmed with a mild COVID-19. Overall, depressive and anxiety symptoms were significantly and marginally increased in patients, respectively, with higher scores in cases with severe and moderate ataxia. Positive patient's impression of psychopathological changes was associated to increased age, age at onset, and anxiety. Sixty-seven patients had a positive self-perception of ataxia progression, which was mainly influenced by higher anxiety scores but not by the adherence to at-home exercise programs. However, the practice of physical exercise was related with lower depression and anxiety scores, but this therapeutical effect was not significantly influenced by the disease stage. We demonstrated the negative effect of the COVID-19 pandemic on the mental and motor deficits in Cuban patients with cerebellar ataxias and the positive effect of the at-home physical exercise programs on their mental well-being. These findings give rationales to develop tele-medicine approaches to minimize these health impacts and to study the long-term effects of such sequelae and accordingly define their treatments.

Founder Effects of Spinocerebellar Ataxias in the American Continents and the Caribbean.

Spinocerebellar ataxias (SCAs) comprise a heterogeneous group of autosomal dominant disorders. The relative frequency of the different SCA subtypes varies broadly among different geographical and ethnic groups as result of genetic drifts. This review aims to provide an update regarding SCA founders in the American continents and the Caribbean as well as to discuss characteristics of these populations. Clusters of SCAs were detected in Eastern regions of Cuba for SCA2, in South Brazil for SCA3/MJD, and in Southeast regions of Mexico for SCA7. Prevalence rates were obtained and reached 154 (municipality of Báguano, Cuba), 166 (General Câmara, Brazil), and 423 (Tlaltetela, Mexico) patients/100,000 for SCA2, SCA3/MJD, and SCA7, respectively. In contrast, the scattered families with spinocerebellar ataxia type 10 (SCA10) reported all over North and South Americas have been associated to a common Native American ancestry that may have risen in East Asia and migrated to Americas 10,000 to 20,000 years ago. The comprehensive review showed that for each of these SCAs corresponded at least the development of one study group with a large production of scientific evidence often generalizable to all carriers of these conditions. Clusters of SCA populations in the American continents and the Caribbean provide unusual opportunity to gain insights into clinical and genetic characteristics of these disorders. Furthermore, the presence of large populations of patients living close to study centers can favor the development of meaningful clinical trials, which will impact on therapies and on quality of life of SCA carriers worldwide.

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.

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.

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.

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.

Spinocerebellar ataxia type 2: Measures of saccade changes improve power for clinical trials.

BACKGROUND: Saccadic eye movement abnormalities are common in patients with spinocerebellar ataxia type 2, but it is unclear how these alterations progress over time. The aim of this study was to assess the progression of saccade involvement in spinocerebellar ataxia type 2 patients, identify its main determinants, and evaluate its usefulness as outcome measures in clinical trials. METHODS: A prospective 5-year follow-up study was performed with 30 spinocerebellar ataxia type 2 patients and their matched healthy controls, who were evaluated a total of four times by clinical and electrooculographical assessments of horizontal saccades and by the scoring of ataxia. RESULTS: Patients showed significant decreases in saccade peak velocity and saccade accuracy as well as increases of saccadic latency during the follow-up period. Annual progression rates were significantly higher in patients compared to controls. Faster progression rates of saccade slowing were associated with higher trinucleotide cytosine-adenine-guanine repeat expansions. Sample-size estimates for two-arm trials would require 19 patients per group to detect a 50% reduction in disease progression using saccade peak velocity as outcome variable, but 44 and 124 patients using saccade latency and accuracy, respectively (power, 80%; alpha = 0.05). CONCLUSIONS: Electrooculographical measures of saccade changes are useful for the objective quantification of disease course in spinocerebellar ataxia type 2. The progression rate of saccade slowing is influenced by the expansion size, providing novel insight into the cumulative polyglutamine neurotoxicity, and supporting the usefulness of saccade peak velocity as a sensitive biomarker during the natural history of the disease, and as suitable outcome measure for therapeutic trials.

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.

Executive deficit in spinocerebellar ataxia type 2 is related to expanded CAG repeats: evidence from antisaccadic eye movements.

Although antisaccadic task is a sensitive research tool in psychopathology, it has not been systematically studied in patients with spinocerebellar ataxia type 2 (SCA2). To identify putative biomarkers of executive dysfunction in SCA2 we assessed the antisaccade performance in 41 SCA2 patients and their sex-and-age matched controls using an electronystagmography device. We studied the relationship between findings in the antisaccade task and CAG repeat length and motor function as assessed using the Scale for the Assessment and Rating of Ataxia (SARA), Nine-Hole Pegboard Test and a validated battery for executive dysfunctions. SCA2 patients showed a significant increase of inhibition and omission antisaccadic error rates, decrease of corrected antisaccadic errors and prolongation of antisaccadic latency and antisaccadic correction latency. Multiple regression predictions identified the expanded CAG repeat as a significant contributing factor on inhibition antisaccadic error rate and percentage of corrected antisaccadic errors. Impaired antisaccadic performance was associated to higher Stroop interference task and verbal fluency test deficits. In conclusion, antisaccadic eye movement abnormalities are a newly recognized association with the genetic abnormality in SCA2 and correlate with executive dysfunction in SCA2. Antisaccade parameters are a promising source of cognitive biomarkers for exploring the disease pathophysiology, and assessing the efficacy of therapeutic options.

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.

Sleep disorders in spinocerebellar ataxia type 2 patients.

BACKGROUND: Sleep disturbances are common features in spinocerebellar ataxias (SCAs). Nevertheless, sleep data on SCA2 come from scarce studies including few patients, limiting the evaluation of the prevalence and determinants of sleep disorders. OBJECTIVE: To assess the frequency and possible determinants of sleep disorders in the large and homogeneous SCA2 Cuban population. METHODS: Thirty-two SCA2 patients and their age- and sex-matched controls were studied by video-polysomnography and sleep interviews. RESULTS: The most striking video-polysomnography features were rapid eye movement (REM) sleep pathology and periodic leg movements (PLMs). REM sleep abnormalities included a consistent reduction of the REM sleep percentage and REM density as well as an increase in REM sleep without atonia (RWA). REM sleep and REM density decreases were closely related to the increase in ataxia scores, whereas the RWA percentage was influenced by the cytosine-adenine-guanine (CAG) repeats. PLMs were observed in 37.5% of cases. The PLM index showed a significant association with the ataxia score and disease duration but not with CAG repeats. CONCLUSIONS: REM sleep pathology and PLMs are closely related to SCA2 severity, suggesting their usefulness as disease progression markers. The RWA percentage is influenced by the CAG repeats and might thus be a sensitive parameter for reflecting polyglutamine toxicity. Finally, as PLMs are sensible to drug treatment, they represents a new therapeutic target for the symptomatic treatment of SCA2.

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.

Hereditary Ataxias in Cuba: Results and Impact of a Comprehensive, Multidisciplinary Project.

Spinocerebellar ataxia type 2 is a degenerative disease that causes physical disability and, ultimately, prostration and death. Globally, reported prevalence is around 3 cases per 100,000 population and Cuba has the world's highest rates of the disease, affecting both patients and their at-risk descendants. In Holguín Province, which has the country's highest concentration of cases, incidence is 4.4 per 100,000 population and prevalence is 40.2 per 100,000 population. In 2000, a specialized research center was established in that province. Supplied with the necessary equipment and human resources, the center conducted national multidisciplinary studies involving molecular biology, clinical care, epidemiology, psychology, clinical neurophysiology, imaging, clinical genetics and community medicine, among others. A training and continuing education program also raised scientific capacity. Priority was given to developing international collaborations for academic exchange and training of Cuban researchers.Multiple results from research involving clinical and epidemiologic characterization of the disease, identification of biomarkers and therapeutic targets, genetic association studies, clinical trials and characterization of the disease's preclinical stages have been introduced in care of patients and their at-risk descendants. This has been accomplished through various programs including personalized rehabilitation, predictive diagnosis and social services. These results have also been published in high-impact scientific journals and received national and international awards. Such an experience in the context of Cuba's national health system-which is universal, free, accessible, comprehensive, prevention-oriented and with a record of international cooperation-demonstrates the possibility of providing quality care to affected families. Incorporating research findings into medical practice, with the resulting impact on patients' health and wellbeing, is a practical example of translational medicine in Cuba. KEYWORDS Spinocerebellar ataxia type 2, health services research, biomedical research. health care delivery, translational medicine, translational research, health equity, Cuba.

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.

Sleep spindles and K-complex activities are decreased in spinocerebellar ataxia type 2: relationship to memory and motor performances.

BACKGROUND: Sleep spindles and K-complexes are electroencephalographic hallmarks of non-rapid eye movement (non-REM) sleep that provide valuable information into brain functioning, plasticity and sleep functions in normal and pathological conditions. However, they have not been systematically investigated in spinocerebellar ataxias (SCA). To close this gap, the current study was carried out to quantify sleep spindles and K-complexes in SCA2 and to assess their relationship with clinical and molecular measures, as well as with memory and attention/executive functioning. METHODS: In this study, 20 SCA2 patients, 20 preclinical carriers and 20 healthy controls underwent whole-night polysomnographic (PSG) recordings as well as sleep interviews, ataxia scoring and neuropsychological assessments. Sleep spindles and K-complexes were automatically detected during non-REM sleep stage 2 (N2). Their densities were evaluated as events/minute. RESULTS: Compared to controls, sleep spindle density was significantly reduced in SCA2 patients and preclinical subjects. By contrast, K-complex density was specifically and significantly decreased only in SCA2 patients. Reduced spindle activity correlated with measures of verbal memory, whereas reduced K-complex activity correlated with age, ataxia severity and N3 sleep percentage in SCA2 patients. CONCLUSIONS: Findings document an impairment of N2 sleep microstructure in SCA2 already in prodromal stages, suggesting an early involvement of thalamo-cortical and/or cortical circuits underlying the generation of sleep spindles and K-complexes. Thus, sleep spindle density may serve as useful biomarker for deficits of neural plasticity mechanisms underlying verbal memory alterations in patients. It may also serve as promising outcome measure in further therapeutical trials targeting memory decline in SCA2. With regard to K-complexes, they have potential usefulness as marker of sleep protection.

Masaje terapéutico para estudiantes universitarios con estrés / Therapeutic massage for college students with stress / Therapeutic massage for college students with stress / Massagem terapêutica para estudantes universitários com estresse

Introducción: El estrés psíquico en los estudiantes universitarios de Licenciatura en Turismo puede provocar manifestaciones negativas en el orden psíquico, físico y social. Objetivo: Exponer la validez de un procedimiento de masaje terapéutico que contribuya a disminuir el estrés psíquico en los estudiantes de Licenciatura en Turismo en la Universidad de Holguín. Método: Se realizó una investigación cuantitativa, se utilizaron métodos teóricos y empíricos; para el procesamiento de los datos se utilizó la estadística matemática. Se seleccionaron 17 expertos para la valoración del procedimiento empleado, con una experiencia promedio de 17 años, la investigación fue de septiembre 2019 a julio 2022. Se seleccionó una muestra de 82 estudiantes, a la cual se le aplicó un test antes y después de concluir el tratamiento con masaje terapéutico. Resultados: Mediante la observación a los estudiantes en los diferentes contextos de actuación y la revisión de las fuentes de información se evidenció resultados indicadores de estrés psíquico. En encuesta aplicada a los profesores, se demostró pocos conocimientos teóricos y metodológicos para la aplicación del masaje terapéutico para estudiantes universitarios con estrés psíquico. Conclusiones: El procedimiento elaborado para disminuir el estrés se aplicó y demuestra su efectividad en la salud y el bienestar de la muestra seleccionada.(AU)

Introduction: Psychological stress in university students studying Bachelor of Tourism can cause negative manifestations in the psychological, physical and social order. Objective: To present the validity of a therapeutic massage procedure that contributes to reducing psychological stress in Bachelor of Tourism students at the University of Holguín. Method: A quantitative research was carried out, theoretical and empirical methods were used.Mathematical statistics were used to process the data.17 experts were selected to evaluate the procedure used, with an average experience of 17 years. The research was from September 2019 to July 2022. A sample of 82 students was selected, to whom a pre-test was applied before treatment,with therapeutic massage, and a post-test at the end. Results: By observing the students in the different contexts of action and reviewing the sources of information, results indicative of psychological stress were evident.In a survey administered to teachers, little theoretical and methodological knowledge was demonstrated for the application of therapeutic massage for university students with psychological stress. Conclusions: The procedure developed to reduce stress was applied and demonstrate its effectiveness on the health and well-being of the selected sample.(AU)

Introdução: O estresse psicológico em estudantes universitários do Bacharelado em Turismo pode causar manifestações negativas de ordem psicológica, física e social. Objetivo: Apresentar a validade de um procedimento de massagem terapêutica que contribui para a redução do estresse psicológico em estudantes do Bacharelado em Turismo da Universidade de Holguín. Método: Foi realizada uma pesquisa quantitativa, foram utilizados métodos teóricos e empíricos.Estatística matemática foi usada para processar os dados.Para avaliar o procedimento utilizado foram selecionados 17 especialistas, com experiência média de 17 anos. A pesquisa ocorreu de setembro de 2019 a julho de 2022. Foi selecionada uma amostra de 82 estudantes, aos quais foi aplicado um pré-teste antes do tratamento com massagem terapêutica, e um pós-teste no final. Resultados: Ao observar os estudantes nos diferentes contextos de atuação e revisar as fontes de informação, ficaram evidentes resultados indicativos de estresse psicológico.Em pesquisa realizada com professores, foi demonstrado pouco conhecimento teórico e metodológico para a aplicação da massagem terapêutica em estudantes universitários com estresse psicológico. Conclusões: O procedimento desenvolvido para reduzir o estresse foi aplicado e demonstrou sua eficácia na saúde e no bem-estar da amostra selecionada.(AU)