State-dependent alterations in neural activity induced by the personalized ventrolateral prefrontal cortex stimulation during viewing emotional film clips.

Emotion regulation is crucial for maintaining normal social interactions and individual psychological health. Using transcranial magnetic stimulation (TMS) to modulate emotional regulation may be a powerful method for neurological or psychiatric disorders. However, TMS efficacy varies between protocols and individuals, with the brain's state during treatment being an often-overlooked factor.

Disrupted periodic spatiotemporal pattern and dynamic reorganization of its basic states in generalized epilepsy.

Objective: The anti-correlation between the default mode network (DMN) and task-positive network (TPN) is a stable characteristic of normal brain activity. However, in idiopathic generalized epilepsy (IGE), this anti-correlation is often disrupted and strongly associated with epileptic seizures. This study aims to use periodic spatiotemporal patterns (PSTP) analysis to elucidate the relationship between the DMN-TPN anti-correlation and epileptic activity, providing new insights into the neural mechanisms underlying IGE.

Genesis of additional open state zones in the extended polyQ tract of the ATXN2 gene depends on its length and interruptions localization.

The ATXN2 gene is located on chromosome 12q24.1 and encodes the ataxin-2 protein, which is involved in the regulation of RNA metabolism, protein synthesis, and intracellular signaling. The polyQ tract encoding glutamine can expand, which leads to the development of various neurodegenerative diseases.

Abnormal open states patterns in the ATXN2 DNA sequence depends on the CAG repeats length.

Hereditary ataxias are one of the «anticipation diseases» types. Spinocerebral ataxia type 2 occurs when the number of CAG repeats in the coding region of the ATXN2 gene exceeds 34 or more. In healthy people, the CAG repeat region in the ATXN2 gene usually consists of 22-23 CAG trinucleotides.

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.

Serum S100β 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 S100β 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 S100β in SCA2 and its relationship with molecular, clinical, cognitive, and peripheral inflammatory markers of the disease.

The determinants of COVID-induced brain dysfunctions after SARS-CoV-2 infection in hospitalized patients.

The severity of the pandemic and its consequences on health and social care systems were quite diverse and devastating. COVID-19 was associated with an increased risk of neurological and neuropsychiatric disorders after SARS-CoV-2 infection. We did a cross-sectional study of 3 months post-COVID consequences of 178 Cuban subjects.

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.

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.

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.

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.

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.

Recent advances in lentiviral vectors for gene therapy.

Lentiviral vectors (LVs), derived from human immunodeficiency virus, are powerful tools for modifying the genes of eukaryotic cells such as hematopoietic stem cells and neural cells. With the extensive and in-depth studies on this gene therapy vehicle over the past two decades, LVs have been widely used in both research and clinical trials. For instance, third-generation and self-inactive LVs have been used to introduce a gene with therapeutic potential into the host genome and achieve targeted delivery into specific tissue.

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.

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.

Glutamate, Glutamine, GABA and Oxidative Products in the Pons Following Cortical Injury and Their Role in Motor Functional Recovery.

Brain injury leads to an excitatory phase followed by an inhibitory phase in the brain. The clinical sequelae caused by cerebral injury seem to be a response to remote functional inhibition of cerebral nuclei located far from the motor cortex but anatomically related to the injury site. It appears that such functional inhibition is mediated by an increase in lipid peroxidation (LP).

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.

Involvement of the Auditory Pathway in Spinocerebellar Ataxia Type 7.

Background: Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant disorder caused by a mutation in the ATXN7 gene. The involvement of the brainstem auditory pathway in pathogenesis of this disease has not been systematically assessed.

Aim: To determine involvement of the brainstem auditory pathway in SCA7 patients and its relationship to clinical features of the disease.

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.

Redox Imbalance Associates with Clinical Worsening in Spinocerebellar Ataxia Type 2.

Background: Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease presenting with redox imbalance. However, the nature and implications of redox imbalance in SCA2 physiopathology have not been fully understood.

Objective: The objective of this study is to assess the redox imbalance and its association with disease severity in SCA2 mutation carriers.

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.

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.

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.