Thiago Luiz Russo

Background: Early accurate prediction of upper limb strength recovery after cervical spinal cord injury (SCI) can optimize rehabilitation and research practices. However, no adequately validated, individualized prognostic model exists. Objective: To develop and validate individual prognostic models for predicting Upper Extremity Motor Score (UEMS) recovery after cervical SCI. Methods: We developed and internally validated prognostic models using data from 423 patients from the European Multicenter Study about Spinal Cord Injury (EMSCI) collaboration. Predictors included UEMS at week 1/week 4 and American Spinal Injury Association Impairment Scale (AIS) category. Ordinal regression models to predict UEMS at 4, 12, 24, and 48 weeks were developed and internally validated using bootstrap-based stability plots. External validation of the 12-week model was performed using a North American cohort of 365 patients. Performance metrics included overall fit and calibration. Results: Internal validation showed stable predictions, good and stable calibration curves, and low prediction errors for all models. At external validation, the model demonstrated good overall fit ( R ² = .81, 95% confidence interval [CI] [0.77 to 0.85]; MAPE = 4.77, 95% CI [4.28 to 5.28]), and good calibration (intercept = 1.10, 95% CI [−0.08 to 2.41]; slope = 1.01, 95% CI [0.97 to 1.05]). The calibration curve indicated a minor underestimation of UEMS for lower predicted values. Conclusions: Simple individualized prognostic models based solely on AIS category and early UEMS allow accurate predictions of upper limb strength recovery after cervical SCI. Our models contribute to expanding the existing literature on motor recovery patterns and prognosis/prediction after cervical SCI. If further validated, these models can inform early clinical decision-making, patient referral and counselling, and clinical trial eligibility.

Background: Currently, there is a considerable number of studies addressing vagus nerve stimulation (VNS) for the treatment of different stroke-related outcomes. We aimed to promote a broad view of the outcomes studied and what are the opportune outcomes to be studied involving this therapeutic strategy for the treatment of post-stroke complications. Methods: This is a scoping review that followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Two investigators conducted independent searches on PubMed/MEDLINE, Scopus, and Embase till July 2025. Randomized clinical trials and preclinical studies using invasive or non-invasive vagus nerve stimulation conducted with a population diagnosed with stroke were included. Results: Forty-one experimental studies and sixteen clinical trials were included. The outcomes found were neuroprotection; motor, functional, and cognitive rehabilitation; dysphagia; comparison of different stimulation intensities; safety, efficacy, and feasibility of the non-invasive approach; comparison between transcutaneous auricular vagus nerve stimulation (taVNS) and transcutaneous cervical vagus nerve stimulation (tcVNS); and comparison between two models of ischemia (permanent and transient). Preclinical studies mostly investigated molecular elements involved in neuroprotection, neuroinflammation, and cellular apoptosis, while clinical studies evaluating the effectiveness of this technique used for rehabilitation and its comparison or combination with other techniques remain scarce. Conclusions: Most studies investigating the effects of VNS on different post-stroke outcomes are experimental studies. Clinical studies are still scarce and with limited analysis of outcomes.

Spaceflight and ground-based models cause fluidshift to the upper part of the body, especially the head. Intracranial compliance (ICC) and cardiovascular autonomic modulation (CAM) can be impacted, impairing cerebral blood flow. ICC is poorly explored but important for astronauts’ health. Also, microgravity can reduce brain activity and affect cerebral functions. Fluidshift models are relevant for understanding its effects and the most used one is head-down tilt (HDT). Thus, this study aimed to investigate the immediate effects of HDT at -6º and − 15º on ICC, CAM and brain oscillations in healthy individuals. Sixty-one subjects (22 females) participated in the study (age 32.7 ± 6.2 years). The 30-minute HDT protocol was performed at -6º and − 15º. ICC was assessed non-invasively through the strain gauge sensor, from brain4care system, along with CAM and cortical activity during cognitive and motor tests. Participants had an increase in the ICP P2/P1 ratio when comparing pre and HDT at -6º (p = 0.004) and a trend toward elevation at -15º (p = 0.058). The sympathetic component of CAM was predominant in both HDT, and brain oscillations were reduced in most tests. The study suggests that acute HDT can reduce ICC, altering sympathovagal balance and causing cortical inhibition.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder primarily characterized by motor impairments resulting from dopaminergic neuron degeneration in the substantia nigra. However, PD is increasingly recognized as a multisystem disorder, where non-motor symptoms such as cognitive impairment, mood disturbances, sleep disorders, and autonomic dysfunction significantly impact patients’ quality of life. These non-motor symptoms often exhibit poor responsiveness to traditional dopaminergic therapies, underscoring a critical gap in current treatment strategies. Our systematic review investigates established methods of PD induction in rodent models and evaluates the methodologies used to assess non-motor symptoms. The review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and the Cochrane handbook. Thirty-two studies from 832 articles were included. The studies were characterized by MPTP, 6-OHDA, and rotenone. Our results indicate that there was considerable heterogeneity in behavioral and motor tests, which poses challenges for data comparability and highlights the lack of consensus regarding the most appropriate modeling strategies for specific PD-related behavioral outcomes. All three models demonstrated behavioral changes consistent with dopaminergic impairment when compared to control groups. MPTP-induced models showed significant non-motor deficits across various tests, except in social recognition and novelty-suppressed feeding. The 6-OHDA model consistently produced non-motor impairments, supporting its utility in replicating PD-like neurotoxicity. Rotenone-treated animals exhibited reduced social interaction, decreased sucrose preference, and increased immobility in behavioral assays, further supporting its validity. Overall, our findings indicate that these neurotoxin-based models are effective in reproducing non-motor symptoms of PD, though methodological heterogeneity highlights the need for greater standardization in future preclinical research.

Background: The microgravity environment has a direct impact on the cardiovascular system due to the fluid shift and weightlessness that results in cardiac dysfunction, vascular remodeling, and altered Cardiovascular autonomic modulation (CAM), deconditioning and poor performance on space activities, ultimately endangering the health of astronauts.Objective: This study aimed to identify the acute and chronic effects of microgravity and Earth analogues on cardiovascular anatomy and function and CAM.Methods: CINAHL, Cochrane Library, Scopus, Science Direct, PubMed, and Web of Science databases were searched. Outcomes were grouped into cardiovascular anatomic, functional, and autonomic alterations, and vascular remodeling. Studies were categorized as Spaceflight (SF), Chronic Simulation (CS), or Acute Simulation (AS) based on the weightlessness conditions. Meta-analysis was performed for the most frequent outcomes. Weightlessness and control groups were compared.Results: 62 articles were included with a total of 963 participants involved. The meta-analysis showed that heart rate increased in SF [Mean difference (MD) = 3.44; p = 0.01] and in CS (MD = 4.98; p < 0.0001), whereas cardiac output and stroke volume decreased in CS (MD = −0.49; p = 0.03; and MD = −12.95; p < 0.0001, respectively), and systolic arterial pressure decreased in AS (MD = -5.20; p = 0.03). According to the qualitative synthesis, jugular vein cross-sectional area (CSA) and volume were greater in all conditions, and SF had increased carotid artery CSA. Heart rate variability and baroreflex sensitivity, in general, decreased in SF and CS, whereas both increased in AS.Conclusion: This review indicates that weightlessness impairs the health of astronauts during and after spaceflight, similarly to the effects of aging and immobility, potentially increasing the risk of cardiovascular diseases.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, identifier CRD42020215515.

Purpose: An FDA-approved non-invasive intracranial pressure (ICP) monitoring system enables the assessment of ICP waveforms by revealing and analyzing their morphological variations and parameters associated with intracranial compliance, such as the P2/P1 ratio and time-to-peak (TTP). The aim of this study is to characterize intracranial compliance in healthy volunteers across different age groups. Methods: Healthy participants, both sexes, aged from 9 to 74 years old were monitored for 5 min in the supine position at 0º. Age was stratified into 4 groups: children (≤ 7 years); young adults (18 ≤ age ≤ 44 years); middle-aged adults (45 ≤ age ≤ 64 years); older adults (≥ 65 years). The data obtained was the non-invasive ICP waveform, P2/P1 ratio and TTP. Results: From December 2020 to February 2023, 188 volunteers were assessed, of whom 104 were male, with a median (interquartile range) age of 41 (29–51), and a median (interquartile range) body mass index of 25.09 (22.57–28.04). Men exhibited lower values compared to women for both the P2/P1 ratio and TTP (p < 0.001). There was a relative rise in both P2/P1 and TTP as age increased (p < 0.001). Conclusions: The study revealed that the P2/P1 ratio and TTP are influenced by age and sex in healthy individuals, with men displaying lower values than women, and both ratios increasing with age. These findings suggest potential avenues for further research with larger and more diverse samples to establish reference values for comparison in various health conditions. Trial registration: Brazilian Registry of Clinical Trials (RBR-9nv2h42), retrospectively registered 05/24/2022. UTN: U1111-1266-8006.

Background Patients with severe coronavirus disease-19 (COVID-19) may require the use of invasive mechanical ventilation (MV) for prolonged periods. Aggressive MV parameters have been associated with changes in intracranial pressure (ICP) in patients with acute intracranial disorders. Significant ICP elevation could compromise intracranial compliance (ICC) and cerebrovascular hemodynamics (CVH). However, the effects of these parameters in individuals without neurological disorders have not yet been evaluated. Objective To evaluate ICC in patients on MV with COVID-19 infection compared to other diagnoses, to better characterize the effects of MV and COVID-19 upon ICC. We also compared between the ICC in patients with COVID-19 who did not require MV and healthy volunteers, to assess the isolated effect of COVID-19 upon ICC. Methods This was an exploratory, observational study with a convenience sample. The ICC was evaluated with a noninvasive ICP monitoring device. The P2/P1 ratio was calculated by dividing the amplitude of these two points, being defined as “abnormal” when P2 > P1. The statistical analysis was performed using a mixed linear model with random effects to compare the P2/P1 ratio in all four groups on the first monitoring day. Results A convenience sample of 78 subjects (15 MV-COVID-19, 15 MV non-COVID-19, 24 non-MV-COVID-19, and 24 healthy participants) was prospectively enrolled. There was no difference in P2/P1 ratios between MV patients with and without COVID-19, nor between non-MV patients with COVID-19 and healthy volunteers. However, the P2/P1 ratio was higher in COVID-19 patients with MV use than in those without it. Conclusion This exploratory analysis suggests that COVID-19 does not impair ICC.

The stroke is the neurological disease with the greatest loss of disability-adjusted life years (DALYs), accounting for almost half of the global burden of neurological diseases.1 Numerous risk fac...

Objetivo: Determinar quais biomarcadores têm sido relacionados à funcionalidade do membro superior na fase aguda, subaguda ou crônica de pessoas que sofreram acidente vascular cerebral (AVC) isquêmico ou hemorrágico. Métodos: Protocolo de revisão sistemática, registrado no PROSPERO (CRD42021274244), com busca de dados sem corte de tempo na PubMed, PubMed PMC, Embase, Web of Science, Scopus, Cinahl e ProQuest. Os revisores avaliarão independentemente títulos, resumos e artigos de texto completo recuperados de bases de dados para identificar estudos potencialmente elegíveis. Os artigos relevantes serão avaliados quanto ao risco de viés e qualidade por meio do uso da ferramenta Quality In Prognosis Studies (QUIPS). A revisão incluirá estudos primários (original), do tipo Ensaios Controlados ou Observacionais (transversal, caso-controle ou estudos longitudinais) com análises de biomarcadores nas diferentes fases de AVC quanto à funcionalidade ou predição de recuperação. Serão excluídos pacientes com menos de 18 anos, diagnóstico de ataque isquêmico transitório e artigos que não explicitam os critérios de forma detalhada da avaliação dos biomarcadores. A qualidade e o risco de viés dos estudos serão avaliados de forma independente por dois pesquisadores. A síntese de dados será realizada utilizando um resumo narrativo e uma análise quantitativa. Modelos de meta-análise de efeitos aleatórios poderão ser empregados com base nas variáveis de resultados encontrados.