RESUMO

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.

RESUMO

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.

Assuntos

RESUMO

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.

Assuntos

RESUMO

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

Assuntos

RESUMO

Transcranial magnetic stimulation (TMS) is a valuable technique to assess and modulate human brain function in normal and pathological conditions. This critical review surveys the contributions of TMS to the diagnosis, insight into pathophysiology and treatment of genetically confirmed hereditary ataxias, a heterogeneous group of neurodegenerative disorders that can affect motor cortex and the corticospinal tract. Most studies were conducted on small sample sizes and focused on diagnostic approaches. The available data demonstrate early involvement of the corticospinal tract and motor cortex circuitry, and support the possible efficacy of cerebellar repetitive TMS (rTMS) as therapeutic approach. Further TMS-based studies are warranted, to establish biomarkers for early diagnosis and disease monitoring, explore the involvement of the cerebello-dentato-thalamo-cortical projection, study the effects of rTMS-induced plasticity, and utilize rTMS for treatment.

Assuntos

RESUMO

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.

Assuntos

Assuntos

RESUMO

We assessed maximal saccade velocity (MSV) in 82 spinocerebellar ataxia type 2 (SCA2) patients and 80 controls, correlating it to disease duration, polyglutamine expansion size, age at onset, ataxia score, age, and sex. Little overlap with normal values was found even at earliest stages. Stepwise linear regression analysis showed that 60-degree MSV was strongly influenced by polyglutamine size and less by disease duration, whereas the reverse was found for ataxia score. Saccade velocity thus is a sensitive, quite specific, and objective endophenotype, useful to search polyglutamine modifier genes.

Assuntos