Structural Brain Correlates of Sleep Microstructure in Spinocerebellar Ataxia Type 2 and its Role on Clinical Phenotype.

The influence of brain atrophy on sleep microstructure in Spinocerebellar Ataxias (SCAs) has not been extensively explored limiting the use of these sleep traits as surrogate biomarkers of neurodegeneration and clinical phenotype. The objective of the study is to explore the relationship between sleep microstructure and brain atrophy in SCA2 and its role in the clinical phenotype. Fourteen SCA2 mutation carriers (7 pre-manifest and 7 manifest subjects) underwent polysomnographic, structural MRI, and clinical assessments. Particularly, markers of REM and non-REM sleep microstructure, measures of cerebellar and brainstem atrophy, and clinical scores were analyzed through correlation and mediation analyses. The sleep spindle activity exhibited a negative correlation with the number of trials required to complete the verbal memory test (VMT), and a positive correlation with the cerebellar volume, but the significance of the latter correlation did not survive multiple testing corrections. However, the causal mediation analyses unveiled that sleep spindle activity significantly mediates the association between cerebellar atrophy and VMT performance. Regarding REM sleep, both phasic EMG activity and REM sleep without atonia exhibited significant associations with pontine atrophy and disease severity measures. However, they did not demonstrate a causal mediation effect between the atrophy measures and disease severity. Our study provides evidence about the association of the pontocerebellar atrophy with sleep microstructure in SCA2 offering insights into the cerebellar involvement in cognition via the control of the sleep spindle activity. Therefore, our findings may help to understand the disease pathogenesis and to better characterize sleep microstructure parameters as disease biomarkers.Clinical trial registration number (TRN): No applicable.

Serum S100ß Levels Are Linked with Cognitive Decline and Peripheral Inflammation in Spinocerebellar Ataxia Type 2.

Experimental and clinical studies have indicated a potential role of the protein S100ß in the pathogenesis and phenotype of neurodegenerative diseases. However, its impact on spinocerebellar ataxia type 2 (SCA2) remains to be elucidated. The objective of the study is to determine the serum levels of S100ß in SCA2 and its relationship with molecular, clinical, cognitive, and peripheral inflammatory markers of the disease. Serum concentrations of S100ß were measured by enzyme-linked immunosorbent assay in 39 SCA2 subjects and 36 age- and gender-matched controls. Clinical scores of ataxia, non-ataxia symptoms, cognitive dysfunction, and some blood cell count-derived inflammatory indices were assessed. The SCA2 individuals manifested S100ß levels similar to the control group, at low nanomolar concentrations. However, the S100ß levels were directly associated with a better performance of cognitive evaluation within the SCA2 cohort. Moreover, the S100ß levels were inversely correlated with most peripheral inflammatory indices. Indeed, the neutrophil-to-lymphocyte ratio significantly mediated the effect of serum S100ß on cognitive performance, even after controlling for the ataxia severity in the causal mediation analysis. Our findings suggested that, within physiologic concentrations, the protein S100ß exerts a neuroprotective role against cognitive dysfunction in SCA2, likely via the suppression of pro-inflammatory mechanisms.

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.

Peripheral Inflammation Links with the Severity of Clinical Phenotype in Spinocerebellar Ataxia 2.

BACKGROUND: The role of peripheral inflammation in spinocerebellar ataxia type 2 (SCA2) is unknown. OBJECTIVE: The objective of this study was to identify peripheral inflammation biomarkers and their relationship with the clinical and molecular features. METHODS: Blood cell count-derived inflammatory indices were measured in 39 SCA2 subjects and their matched controls. Clinical scores of ataxia, nonataxia, and cognitive dysfunction were assessed. RESULTS: The neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the Systemic Inflammation Index (SII), and the Aggregate Index of Systemic Inflammation (AISI) were significantly increased in SCA2 subjects compared with controls. The increases in PLR, SII, and AISI were even observed in preclinical carriers. NLR, PLR, and SII were correlated with the Scale for the Assessment and Rating of Ataxia speech item score rather than with the total score. The NLR and SII were correlated with the nonataxia and the cognitive scores. CONCLUSIONS: Peripheral inflammatory indices are biomarkers in SCA2, which may help to design future immunomodulatory trials and advance our understanding of the disease. © 2023 International Parkinson and Movement Disorder Society.

An Exploratory Survey on the Care for Ataxic Patients in the American Continents and the Caribbean.

Little is known about access of rare disease carriers to health care. To increase this knowledge, the Pan American Hereditary Ataxia Network (PAHAN) conducted an exploratory survey about care for hereditary ataxias in American continents and the Caribbean. A questionnaire was sent to health professionals about the hereditary ataxias identified; access to care; and local teaching and research. The number of ataxics under current care per 100,000 inhabitants was subtracted from the expected overall prevalence of 6/100,000, to estimate the prevalence of uncovered ataxic patients. Local Human Development Indexes (HDI) were used to measure socio-economic factors. Twenty-six sites participated. Twelve sites had very high, 13 had high, and one site had medium HDI. Participants reported on 2239 and 602 patients with spinocerebellar ataxias and recessive forms under current care. The number of patients under current care per inhabitants varied between 0.14 and 12/100,000. The estimated prevalence of uncovered ataxic patients was inversely proportional to HDIs (rho = 0.665, p = 0.003). Access to diagnosis, pre-symptomatic tests, and rehabilitation were associated with HDIs. More and better molecular diagnostic tools, protocols and guidelines, and professional training for ataxia care were the top priorities common to all respondents. Evidence of inequalities was confirmed. Lower HDIs were associated with high potential numbers of uncovered ataxic subjects, and with lack of molecular diagnosis, pre-symptomatic testing, and rehabilitation. More and better diagnostic tools, guidelines, and professional training were priorities to all sites. PAHAN consortium might help with the last two tasks.

ConvNets for automatic detection of polyglutamine SCAs from brain MRIs: state of the art applications.

Polyglutamine spinocerebellar ataxias (polyQ SCAs) are a group of neurodegenerative diseases, clinically and genetically heterogeneous, characterized by loss of balance and motor coordination due to dysfunction of the cerebellum and its connections. The diagnosis of each type of polyQ SCA, alongside with genetic tests, includes medical images analysis, and its automation may help specialists to distinguish between each type. Convolutional neural networks (ConvNets or CNNs) have been recently used for medical image processing, with outstanding results. In this work, we present the main clinical and imaging features of polyglutamine SCAs, and the basics of CNNs. Finally, we review studies that have used this approach to automatically process brain medical images and may be applied to SCAs detection. We conclude by discussing the possible limitations and opportunities of using ConvNets for SCAs diagnose in the future.

Bibliometría y mapeo de redes de la producción científica internacional de Cuba sobre ataxias (1993-2020) / Bibliometrics and network mapping of Cuban international scientific production on ataxias (1993-2020)

El objetivo del estudio fue caracterizar el potencial investigador cubano en el ámbito de las ataxias y su evolución temporal. Se realizó una búsqueda en la base de datos Web of Science y se obtuvieron todos los documentos publicados entre 1993 y 2020. Se aplicaron indicadores bibliométricos para explorar la producción, dispersión, distribución y crecimiento anual de los documentos (ley de Price, ley de Lotka, índice de transitoriedad y modelo de Bradford). Se calculó el índice de participación y colaboración de países e instituciones y, por cartografía bibliométrica, se exploraron las redes de coocurrencia de los términos más utilizados. La producción científica de Cuba sobre ataxias hereditarias es alta (219 documentos) y se ajusta a un crecimiento lineal (r= 0,7580). El período estudiado concentra el 47,95 por ciento de los registros con un ritmo anual de publicaciones del 6,6 por ciento y tiempo de duplicidad de 10,8 años. El total de citas fue de 3807 (índice medio: 131,27; índice -h: 31). Se concluye que el crecimiento de la literatura científica cubana sobre ataxias fue lineal para el período estudiado, lo que confirma el incumplimiento de la ley de Price de crecimiento de la literatura científica. El estudio también corrobora la importante red de integración y cooperación internacional entre los diferentes autores y la interdisciplinariedad de los trabajos, evidencia del éxito del Centro para la Investigación y Rehabilitación de las Ataxias Hereditarias (CIRAH), al planificar una estrategia de colaboración científica con objetivos definidos(AU)

The objective of this study was to characterize the Cuban research potential in the field of ataxias and its temporal evolution. A search was carried out in the Web of Science database and all the documents published from 1993 to 2020 were retrieved. Bibliometric indicators were applied to explore the production, dispersion, distribution and annual growth of the documents (Price's law, Lotka's law, transience index and Bradford model). The participation and collaboration index of countries and institutions was calculated and, through bibliometric cartography, the co-occurrence networks of the most used terms were explored. The Cuban scientific production on hereditary ataxias is high (219 documents) and it adjusts to a linear growth (r = 0.7580). The period studied concentrates 47.95percent of the records with an annual publication rate of 6.6percent and 10.8 years' duplication time. The total number of citations was 3807 (mean index: 131.27; h-index: 31). Growth of the Cuban scientific literature on ataxias was concluded to be linear for the period studied, which confirms the non-compliance with Price's law of growth of scientific literature. The study also corroborates the important network of integration and international cooperation among the different authors and the interdisciplinarity of the papers, marking the success of the Center for Research and Rehabilitation of Hereditary Ataxias (CIRAH), when planning a strategy of scientific collaboration with objectives defined(AU)

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.

Convolutional Neural Networks for Segmenting Cerebellar Fissures from Magnetic Resonance Imaging.

The human cerebellum plays an important role in coordination tasks. Diseases such as spinocerebellar ataxias tend to cause severe damage to the cerebellum, leading patients to a progressive loss of motor coordination. The detection of such damages can help specialists to approximate the state of the disease, as well as to perform statistical analysis, in order to propose treatment therapies for the patients. Manual segmentation of such patterns from magnetic resonance imaging is a very difficult and time-consuming task, and is not a viable solution if the number of images to process is relatively large. In recent years, deep learning techniques such as convolutional neural networks (CNNs or convnets) have experienced an increased development, and many researchers have used them to automatically segment medical images. In this research, we propose the use of convolutional neural networks for automatically segmenting the cerebellar fissures from brain magnetic resonance imaging. Three models are presented, based on the same CNN architecture, for obtaining three different binary masks: fissures, cerebellum with fissures, and cerebellum without fissures. The models perform well in terms of precision and efficiency. Evaluation results show that convnets can be trained for such purposes, and could be considered as additional tools in the diagnosis and characterization of neurodegenerative diseases.

Neurophysiological features in spinocerebellar ataxia type 2: Prospects for novel biomarkers.

Electrophysiological biomarkers are useful to assess the degeneration and progression of the nervous system in pre-ataxic and ataxic stages of the Spinocerebellar Ataxia Type 2 (SCA2). These biomarkers are essentially defined by their clinical significance, discriminating patients and/or preclinical subjects from healthy controls in cross-sectional studies, their significant changes over time in longitudinal studies, and their correlation with the cytosine-guanine-adenine (CAG) repeat expansion and/or clinical ataxia scores, time of evolution and time to ataxia onset. We classified electrophysiological biomarkers into three main types: (1) preclinical, (2) disease progression and (3) genetic damage. We review the data that identify sural nerve potential amplitude, maximum saccadic velocity, sleep efficiency, rapid eye movement (REM) sleep percentage, K-complex density, REM sleep without atonia percentage, corticomuscular coherence, central motor conduction time, visual P300 latency, and antisaccadic error correction latency as reliable preclinical, progression and/or genetic damage biomarkers of SCA2. These electrophysiological biomarkers will facilitate the conduction of clinical trials that test the efficacy of emerging treatments in SCA2.

Genetic Distribution of Five Spinocerebellar Ataxia Microsatellite Loci in Mexican Native American Populations and Its Impact on Contemporary Mestizo Populations.

Spinocerebellar ataxias (SCAs) conform a heterogeneous group of neurodegenerative disorders with autosomal dominant inheritance. Five of the most frequent SCAs are caused by a CAG repeat expansion in the exons of specific genes. The SCAs incidence and the distribution of polymorphic CAG alleles vary among populations and ethnicities. Thus, characterization of the genetic architecture of ethnically diverse populations, which have undergone recent admixture and demographic events, could facilitate the identification of genetic risk factors. Owing to the great ethnic diversity of the Mexican population, this study aimed to analyze the allele frequencies of five SCA microsatellite loci (SCA1, SCA2, SCA3, SCA6, and SCA7) in eleven Mexican Native American (MNA) populations. Data from the literature were used to compare the allelic distribution of SCA loci with worldwide populations. The SCA loci allelic frequencies evidenced a certain genetic homogeneity in the MNA populations, except for Mayans, who exhibited distinctive genetic profiles. Neither pathological nor large normal alleles were found in MNA populations, except for the SCA2 pre-mutated allele in the Zapotec population. Collectively, our findings demonstrated the contribution of the MNA ancestry in shaping the genetic structure of contemporary Mexican Mestizo populations. Our results also suggest that Native American ancestry has no impact on the origin of SCAs in the Mexican population. Instead, the acquisition of pathological SCA alleles could be associated with European migration.

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.

Cognitive Decline Is Closely Associated with Ataxia Severity in Spinocerebellar Ataxia Type 2: a Validation Study of the Schmahmann Syndrome Scale.

The cerebellar cognitive affective syndrome scale (CCAS-S) was designed to detect specific cognitive dysfunctions in cerebellar patients but is scarcely validated in spinocerebellar ataxias (SCA). The objective of this study is to determine the usefulness of the CCAS-S in a Cuban cohort of SCA2 patients and the relationship of its scores with disease severity. The original scale underwent a forward and backward translation into Spanish language, followed by a pilot study to evaluate its comprehensibility. Reliability, discriminant, and convergent validity assessments were conducted in 64 SCA2 patients and 64 healthy controls matched for sex, age, and education. Fifty patients completed the Montreal Cognitive Assessment (MoCA) test. The CCAS-S showed an acceptable internal consistency (Cronbach's alpha = 0.74) while its total raw score and the number of failed tests showed excellent (ICC = 0.94) and good (ICC = 0.89) test-retest reliability, respectively. Based on original cut-offs, the sensitivity of CCAS-S to detect possible/probable/definite CCAS was notably high (100%/100%/91%), but specificities were low (6%/30/64%) because the decreased specificity observed in four items. CCAS-S performance was significantly influenced by ataxia severity in patients and by education in both groups. CCAS-S scores correlated with MoCA scores, but showed higher sensitivity than MoCA to detect cognitive impairments in patients. The CCAS-S is particularly useful to detect cognitive impairments in SCA2 but some transcultural and/or age and education-dependent adaptations could be necessary to improve its diagnostic properties. Furthermore, this scale confirmed the parallelism between cognitive and motor deficits in SCA2, giving better insights into the disease pathophysiology and identifying novel outcomes for clinical trials.

Gene Therapy for Polyglutamine Spinocerebellar Ataxias: Advances, Challenges, and Perspectives.

Polyglutamine spinocerebellar ataxias (SCAs) comprise a heterogeneous group of six autosomal dominant ataxias caused by cytosine-adenine-guanine repeat expansions in the coding region of single genes. Currently, there is no curative or disease-slowing treatment for these disorders, but their monogenic inheritance has informed rationales for development of gene therapy strategies. In fact, RNA interference strategies have shown promising findings in cellular and/or animal models of SCA1, SCA3, SCA6, and SCA7. In addition, antisense oligonucleotide therapy has provided encouraging proofs of concept in models of SCA1, SCA2, SCA3, and SCA7, but they have not yet progressed to clinical trials. On the contrary, the gene editing strategies, such as the clustered regularly interspaced short palindromic repeat (CRISPR/Cas9), have been introduced to a limited extent in these disorders. In this article, we review the available literature about gene therapy in polyglutamine SCAs and discuss the main technological and ethical challenges toward the prospect of their use in future clinical trials. Although antisense oligonucleotide therapies are further along the path to clinical phases, the recent failure of three clinical trials in Huntington's disease may delay their utilization for polyglutamine SCAs, but they offer lessons that could optimize the likelihood of success in potential future clinical studies. © 2021 International Parkinson and Movement Disorder Society.

Gait Variability in Spinocerebellar Ataxia Assessed Using Wearable Inertial Sensors.

BACKGROUND: Quantitative assessment of severity of ataxia-specific gait impairments from wearable technology could provide sensitive performance outcome measures with high face validity to power clinical trials. OBJECTIVES: The aim of this study was to identify a set of gait measures from body-worn inertial sensors that best discriminate between people with prodromal or manifest spinocerebellar ataxia (SCA) and age-matched, healthy control subjects (HC) and determine how these measures relate to disease severity. METHODS: One hundred and sixty-three people with SCA (subtypes 1, 2, 3, and 6), 42 people with prodromal SCA, and 96 HC wore 6 inertial sensors while performing a natural pace, 2-minute walk. Areas under the receiver operating characteristic curves (AUC) were compared for 25 gait measures, including standard deviations as variability, to discriminate between ataxic and normal gait. Pearson's correlation coefficient assessed the relationships between the gait measures and severity of ataxia. RESULTS: Increased gait variability was the most discriminative gait feature of SCA; toe-out angle variability (AUC = 0.936; sensitivity = 0.871; specificity = 0.896) and double-support time variability (AUC = 0.932; sensitivity = 0.834; specificity = 0.865) were the most sensitive and specific measures. These variability measures were also significantly correlated with the scale for the assessment and rating of ataxia (SARA) and disease duration. The same gait measures discriminated gait of people with prodromal SCA from the gait of HC (AUC = 0.610, and 0.670, respectively). CONCLUSIONS: Wearable inertial sensors provide sensitive and specific measures of excessive gait variability in both manifest and prodromal SCAs that are reliable and related to the severity of the disease, suggesting they may be useful as clinical trial performance outcome measures. © 2021 International Parkinson and Movement Disorder Society.

Falta de rigor científico de dos investigaciones de series de casos sobre diplomáticos estadounidenses en La Habana / Lack of scientific consistency in two investigations of case series of United States diplomats in Havana

Introducción: Con el propósito de justificar la decisión diplomática de los Estados Unidos, se publicaron dos artículos científicos en revistas médicas que intentan sostener la idea de que en La Habana hubo un ataque dirigido a personal de la embajada estadounidense. Objetivo: Demostrar la falta de rigor científico en dos investigaciones de series de casos no independientes sobre los síntomas de salud de diplomáticos de los Estados Unidos en La Habana. Método: Se realiza un análisis documental de dos publicaciones de series de casos. Se evalúan hipótesis diagnósticas. Resultados: Existe superposición amplia entre las dos series en cuanto a pacientes compartidos y en contraste se presentan algunas diferencias en los datos clínicos que superan lo esperado. Conclusiones: En ambas publicaciones se desaprovecha la riqueza semiográfica de síntomas y la información psicosocial. Se enfatiza más en argumentos asociados al fetichismo de la tecnología expresado en la interpretación de hallazgos inespecíficos. El análisis de datos clínicos permitió ver que se trata de un grupo heterogéneo de personas cuyas quejas de salud han sido reunidas por la interacción de otros factores psicosociales contextuales(AU)

Introduction: In order to justify the diplomatic decision of the United States, two scientific articles were published in medical journals that attempt to support the idea that, in Havana, there was an attack aimed at US embassy personnel. Objective: To prove the lack of scientific consistency in two investigations of non-independent case series on the health symptoms of United States diplomats in Havana. Method: A documentary analysis of two publications of case series is carried out. Diagnostic hypotheses are evaluated. Results: There is wide overlap between the two series in terms of shared patients and in contrast there are some differences in the clinical data that exceed what was expected. Conclusions: In both publications the semiographic wealth of symptoms and psychosocial information are wasted. More emphasis is placed on arguments associated with the fetishism of technology expressed in the interpretation of nonspecific findings. The analysis of clinical data allowed us to see that it is a heterogeneous group of people whose health complaints have been brought together by the interaction of other contextual psychosocial factors(AU)

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.

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.

A hybrid unsupervised-Deep learning tandem for electrooculography time series analysis.

Medical data are often tricky to get mined for patterns even by the generally demonstrated successful modern methodologies of deep learning. This paper puts forward such a medical classification task, where patient registers of two of the categories are sometimes hard to be distinguished because of samples showing characteristics of both labels in turn in several repetitions of the screening procedure. To this end, the current research appoints a pre-processing clustering step (through self-organizing maps) to group the data based on shape similarity and relabel it accordingly. Subsequently, a deep learning approach (a tandem of convolutional and long short-term memory networks) performs the training classification phase on the 'cleaned' samples. The dual methodology was applied for the computational diagnosis of electrooculography tests within spino-cerebral ataxia of type 2. The accuracy obtained for the discrimination into three classes was of 78.24%. The improvement that this duo brings over the deep learner alone does not stem from significantly higher accuracy results when the performance is considered for all classes. The major finding of this combination is that half of the presymptomatic cases were correctly found, in opposition to the single deep model, where this category was sacrificed by the learner in favor of a good accuracy overall. A high accuracy in general is desirable for any medical task, however the correct identification of cases before the symptoms become evident is more important.