The vascular contribution of apolipoprotein E to Alzheimer's disease.

Alzheimer's disease, the most prevalent form of dementia, imposes a substantial societal burden. The persistent inadequacy of disease-modifying drugs targeting amyloid plaques and neurofibrillary tangles suggests the contribution of alternative pathogenic mechanisms. A frequently overlooked aspect is cerebrovascular dysfunction, which may manifest early in the progression of Alzheimer's disease pathology. Mounting evidence underscores the pivotal role of the apolipoprotein E gene, particularly the apolipoprotein ε4 allele as the strongest genetic risk factor for late-onset AD, in the cerebrovascular pathology associated with Alzheimer's disease. In this review, we examine the evidence elucidating the cerebrovascular impact of both central and peripheral apolipoprotein E on the pathogenesis of Alzheimer's disease. We present a novel three-hit hypothesis, outlining potential mechanisms that shed light on the intricate relationship among different pathogenic events. Finally, we discuss prospective therapeutics targeting the cerebrovascular pathology associated with apolipoprotein E and explore their implications for future research endeavors.

Diagnostic value of isolated plasma biomarkers and its combination in neurodegenerative dementias: A multicenter cohort study.

BACKGROUND: Plasma amyloid-ß (Aß), phosphorylated tau-181 (p-tau181), neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) potentially aid in the diagnosis of neurodegenerative dementias. We aim to conduct a comprehensive comparison between different biomarkers and their combination, which is lacking, in a multicenter Chinese dementia cohort consisting of Alzheimer's disease (AD), frontotemporal dementia (FTD), and progressive supranuclear palsy (PSP). METHODS: We enrolled 92 demented patients [64 AD, 16 FTD, and 12 PSP with dementia] and 20 healthy controls (HC). Their plasma Αß, p-tau181, NfL, and GFAP were detected by highly sensitive-single molecule immunoassays. Αß pathology in patients was measured by cerebrospinal fluid or/and amyloid positron emission tomography. RESULTS: All plasma biomarkers tested were significantly altered in dementia patients compared with HC, especially Aß42/Aß40 and NfL showed significant performance in distinguishing AD from HC. A combination of plasma Aß42/Aß40, p-tau181, NfL, and GFAP could discriminate FTD or PSP well from HC and was able to distinguish AD and non-AD (FTD/PSP). CONCLUSIONS: Our results confirmed the diagnostic performance of individual plasma biomarkers Aß42/Aß40, p-tau181, NfL, and GFAP in Chinese dementia patients and noted that a combination of these biomarkers may be more accurate in identifying FTD/PSP patients and distinguishing AD from non-AD dementia.

Exogenous 6-BA enhances salt tolerance of Limonium bicolor by increasing the number of salt glands.

KEY MESSAGE: Exogenous 6-BA can increase endogenous hormone content, improve photosynthesis, decrease Na+ by increasing leaf salt gland density and salt secretion ability, and reduce ROS content so that it can promote L. bicolor growth. 6-benzyl adenine (6-BA) is an artificial cytokinin and has been widely applied to improving plant adaptation to stress. However, it is rarely reported that 6-BA alleviates salt damage of halophytes. In this paper, we treated Limonium bicolor seedlings, a recretohalophyte with high medicinal and ornamental values, with 300 mM NaCl and different concentrations of 6-BA (0.5, 1.0, and 1.5 mg/L) and measured plant growth, physiological index, the density of salt gland, and the salt secretion ability of leaves. The results showed that exogenous applications 1.0 mg/L 6-BA significantly improved plant growth and photosynthesis, increased cytokinin and auxins contents, K+ and organic soluble matter contents, the activities of SOD, CAT, APX, and POD, and decreased Na+, H2O2, and O2- contents compared to that treated with 300 mM NaCl. Further research showed that exogenous 6-BA significantly increased the density of salt gland and the salt secretion ability of leaves by upregulating the expression of the salt gland developmental genes, therefore, can secrete more excess Na+, and thus reduces the Na+ concentration in leaves, which can alleviate Na+ damage to the species. In all, exogenous 1.0 mg/L 6-BA can increase endogenous hormone, improve photosynthesis, decrease Na+ by increasing secretion ability, and reduce ROS content of L. bicolor so that it can improve the growth. These results above systematically prove the new role of 6-BA in salt tolerance of L. bicolor.

Identification of Candidate Biomarkers of Alzheimer's Disease via Multiplex Cerebrospinal Fluid and Serum Proteomics.

Alzheimer's disease (AD) is the most prevalent form of dementia among elderly people worldwide. Cerebrospinal fluid (CSF) is the optimal fluid source for AD biomarkers, while serum biomarkers are much more achievable. To search for novel diagnostic AD biomarkers, we performed a quantitative proteomic analysis of CSF and serum samples from AD and normal cognitive controls (NC). CSF and serum proteomes were analyzed via data-independent acquisition quantitative mass spectrometry. Our bioinformatic analysis was based on Gene Ontology (GO) functional annotation analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. In comparison to the controls, 8 proteins were more abundant in AD CSF, and 60 were less abundant in AD CSF, whereas 55 proteins were more and 10 were less abundant in the serum samples. ATPase-associated activity for CSF and mitochondrial functions for CSF and serum were the most enriched GO terms of the DEPs. KEGG enrichment analysis showed that the most significant pathways for the differentially expressed proteins were the N-glycan biosynthesis pathways. The area under the curve (AUC) values for CSF sodium-/potassium-transporting ATPase subunit beta-1 (AT1B1), serglycin (SRGN), and thioredoxin-dependent peroxide reductase, mitochondrial (PRDX3) were 0.867 (p = 0.004), 0.833 (p = 0.008), and 0.783 (p = 0.025), respectively. A panel of the above three CSF proteins accurately differentiated AD (AUC = 0.933, p = 0.001) from NC. The AUC values for serum probable phospholipid-transporting ATPase IM (AT8B4) and SRGN were moderate. The AUC of the CSF SRGN + serum SRGN was 0.842 (p = 0.007). These novel AD biomarker candidates are mainly associated with inflammation, ATPase activity, oxidative stress, and mitochondrial dysfunction. Further studies are needed to investigate the molecular mechanisms by which these potential biomarkers are involved in AD.

Sleep patterns correlates with the efficacy of tDCS on post-stroke patients with prolonged disorders of consciousness.

BACKGROUND: The subclassification of prolonged disorders of consciousness (DoC) based on sleep patterns is important for the evaluation and treatment of the disease. This study evaluates the correlation between polysomnographic patterns and the efficacy of transcranial direct current stimulation (tDCS) in patients with prolonged DoC due to stroke. METHODS: In total, 33 patients in the vegetative state (VS) with sleep cycles or without sleep cycles were randomly assigned to either active or sham tDCS groups. Polysomnography was used to monitor sleep changes before and after intervention. Additionally, clinical scale scores and electroencephalogram (EEG) analysis were performed before and after intervention to evaluate the efficacy of tDCS on the patients subclassified according to their sleep patterns. RESULTS: The results suggest that tDCS improved the sleep structure, significantly prolonged total sleep time (TST) (95%CI: 14.387-283.527, P = 0.013) and NREM sleep stage 2 (95%CI: 3.157-246.165, P = 0.040) of the VS patients with sleep cycles. It also significantly enhanced brain function of patients with sleep cycles, which were reflected by the increased clinical scores (95%CI: 0.340-3.440, P < 0.001), the EEG powers and functional connectivity in the brain and the 6-month prognosis. Moreover, the changes in NREM sleep stage 2 had a significant positive correlation with each index of the ß band. CONCLUSION: This study reveals the importance of sleep patterns in the prognosis and treatment of prolonged DoC and provides new evidence for the efficacy of tDCS in post-stroke patients with VS patients subclassified by sleep pattern. Trial registration URL: https://www. CLINICALTRIALS: gov . Unique identifier: NCT03809936. Registered 18 January 2019.

Altered Intestinal Microbiomes and Lipid Metabolism in Patients With Prolonged Disorders of Consciousness.

The intestinal microbiota regulate the brain function of the host through the production of a myriad of metabolites and are associated with various neurological diseases. Understanding the intestinal microbiome of patients with prolonged disorders of consciousness (DoC) is important for the evaluation and treatment of the disease. To investigate the differences in the intestinal microbiome and short-chain fatty acids (SCFAs) among patients in a vegetative state (VS), a minimally conscious state (MCS), and emerged from MCS (EMCS), as well as the influence of antibiotics on these patients, 16S ribosomal RNA (16S rRNA) sequencing and targeted lipidomics were performed on fecal samples from patients; in addition, analysis of the electroencephalogram (EEG) signals was performed to evaluate the brain function of these patients. The results showed that the intestinal microbiome of the three groups differed greatly, and some microbial communities showed a reduced production of SCFAs in VS patients compared to the other two groups. Moreover, reduced microbial communities and five major SCFAs, along with attenuated brain functional connectivity, were observed in MCS patients who were treated with antibiotics compared to those who did not receive antibiotic treatment, but not in the other pairwise comparisons. Finally, three genus-level microbiota-Faecailbacterium, Enterococcus, and Methanobrevibacter-were considered as potential biomarkers to distinguish MCS from VS patients, with high accuracy both in the discovery and validation cohorts. Together, our findings improved the understanding of patients with prolonged DoC from the intestinal microbiome perspective and provided a new reference for the exploration of therapeutic targets.

The relationship between a fish-rich diet and poststroke cognitive impairment: A cross-sectional study with a follow-up in China.

ABSTRACT: Whether a fish-rich diet is positively associated with cognitive function after stroke remains unclear; thus, the present study investigated the relationship between them.The present study was part of a prospective multicenter study, in which 920 individuals (609 males, mean age, 62.78 ±â€Š11.79 years) were included from November 2013 to December 2015. The cognitive function of the patients was evaluated, and the diagnosis of poststroke cognitive impairment (PSCI) was made during their stay in the hospital. A subgroup of 439 patients from a single center was followed up for 4 to 6 years and was reassessed for cognitive function.According to the diagnostic criteria, the PSCI prevalence was lower in the fish-rich diet group (P < .05). After adjusting for demographic and clinical variables by logistic regression, patients with a habit of consuming a fish-rich diet had a lower risk of developing PSCI than patients without a fish-rich diet (odds ratio [OR]: 0.74; 95% confidence interval [CI]: 0.46-0.95). When MMSE score was considered the cognitive function outcome variable, the long-term cognitive function of the fish-rich diet group was better (28 [26-30] vs 27 [25-29], P < .01), but the statistical results were not significant after correcting for the related confounding factors (ß: 0.13; 95% CI: -0.99-1.25; P = .82).There was a negative relationship between consuming a fish-rich diet and the prevalence of PSCI, and there was no statistically significant difference in the relationship of a fish-rich diet on long-term cognitive function after stroke, which requires further study.

Serum Metabolites Differentiate Amnestic Mild Cognitive Impairment From Healthy Controls and Predict Early Alzheimer's Disease via Untargeted Lipidomics Analysis.

Background and Aim: Alzheimer's disease (AD) is the most common type of dementia and presents with metabolic perturbations early in the disease process. In order to explore biomarkers useful in predicting early AD, we compared serum metabolites among patients suffering different stages of AD. Methods: We recruited 107 participants including 23 healthy controls (HC), 21 amnestic mild cognitive impairment (aMCI), 24 non-amnestic mild cognitive impairment (naMCI) and 39 AD patients. Via liquid chromatography-mass spectrometry based serum untargeted lipidomics analysis, we compared differences in serum lipid metabolites among these patient groups and further elucidated biomarkers that differentiate aMCI from HC. Results: There were significant differences of serum lipid metabolites among the groups, and 20 metabolites were obtained under negative ion mode from HC and aMCI comparison. Notably, 16:3 cholesteryl ester, ganglioside GM3 (d18:1/9z-18:1) and neuromedin B were associated with cognition and increased the predictive effect of aMCI to 0.98 as revealed by random forest classifier. The prediction model composed of MoCA score, 16:3 cholesteryl ester and ganglioside GM3 (d18:1/9z-18:1) had good predictive performance for aMCI. Glycerophospholipid metabolism was a pathway common among HC/aMCI and aMCI/AD groups. Conclusion: This study provides preliminary evidence highlighting that 16:3 cholesteryl ester were useful for AD disease monitoring while ganglioside GM3 (d18:1/9z-18:1) and neuromedin B discriminated aMCI from HC, which can probably be applied in clinic for early predicting of AD.

Metabolic Abnormalities in Patients with Chronic Disorders of Consciousness.

The vegetative state (VS) and minimally conscious state (MCS) are two major types of chronic disorders of consciousness (DoC). The assessment of these two consciousness states generally relies on the Coma Recovery Scale-Revised (CRS-R) score, but a high misdiagnosis rate limits the generalized use of this score. To identify metabolites in human plasma that can accurately distinguish VS from MCS patients, comprehensive plasma metabolic profiles were obtained with targeted metabolomics analysis and untargeted and targeted lipidomics analysis. Univariate and multivariate analyses were used to assess the significance of differences. Compared with healthy controls (HCs), the DoC groups, Emerged from Minimally Conscious State (EMCS) group and Alzheimer's disease (AD) group had significantly different metabolic profiles. Purine metabolism pathway differed the most between the DoC (MCS and VS) and HC groups. In this pathway, adenosine, ADP, and AMP, which are the derived products of ATP degradation, were decreased in the MCS and VS groups compared to healthy controls. More importantly, we identified certain lipids for which the levels were enriched in the VS or MCS groups. Specifically, phosphatidylcholine, (38:5)-H (PC(38:5)-H), and arachidonic acid (AA) differed substantially between the VS and MCS groups and may be used to distinguish these two groups of patients. Together, our findings suggest that metabolic profiling is significantly altered in patients with chronic DoC.

A multi-domain prognostic model of disorder of consciousness using resting-state fMRI and laboratory parameters.

OBJECTIVES: Although laboratory parameters have long been recognized as indicators of outcome of traumatic brain injury (TBI), it remains a challenge to predict the recovery of disorder of consciousness (DOC) in severe brain injury including TBI. Recent advances have shown an association between alterations in brain connectivity and recovery from DOC. In the present study, we developed a prognostic model of DOC recovery via a combination of laboratory parameters and resting-state functional magnetic resonance imaging (fMRI). METHODS: Fifty-one patients with DOC (age = 52.3 ± 15.2 y, male/female = 31/20) were recruited from Hangzhou Hospital of Zhejiang CAPR and were sub-grouped into conscious (n = 34) and unconscious (n = 17) groups based upon their Glasgow Outcome Scale-Extended (GOS-E) scores at 12-month follow-ups after injury. Resting-state functional connectivity, network nodal measures (centrality), and laboratory parameters were obtained from each patient and served as features for support vector machine (SVM) classifications. RESULTS: We found that functional connectivity was the most accurate single-domain model (ACC: 70.1% ± 4.5%, P = 0.038, 1000 permutations), followed by degree centrality, betweenness centrality, and laboratory parameters. The stacked multi-domain prognostic model (ACC: 73.4% ± 3.1%, P = 0.005, 1000 permutations) combining all single-domain models yielded a significantly higher accuracy compared to that of the best-performing single-domain model (P = 0.002). CONCLUSION: Our results suggest that laboratory parameters only contribute to the outcome prediction of DOC patients, whereas combining information from neuroimaging and clinical parameters may represent a strategy to achieve a more accurate prognostic model, which may further provide better guidance for clinical management of DOC patients.

Presenilin 1 and APP Gene Mutations in Early-Onset AD Families from a Southeast Region of China.

BACKGROUND: Early-Onset Familial Alzheimer's Disease (EOFAD) has been reported to be associated with Presenilin 1 (PSEN1), Presenilin 2 (PSEN2), and Amyloid Precursor Protein (APP) genes. The spectrum of mutations in Chinese patients with EOFAD was rarely investigated. OBJECTIVE: To investigate the spectrum of mutations in patients with EOFAD in Chinese population. METHODS: We performed whole-exome sequencing and described relevant clinical features in a total of 67 subjects from 3 families with EOFAD. RESULTS: A splice mutation (p.S290C) in PSEN1 and a missense mutation (p.V717I) in APP were identified. CONCLUSION: The variant p. S290C (c.869-2>G) in PSEN1 in Chinese EOAD family revealed different clinical phenotypes when compared with that of Europeans.

Low Hemoglobin Levels at Admission Are Independently Associated with Cognitive Impairment after Ischemic Stroke: a Multicenter, Population-Based Study.

Data on the association between hemoglobin (Hb) levels and poststroke cognitive function are limited. We investigated the relationship between Hb concentrations at admission and poststroke cognitive function using a multicenter database. In total, 1081 patients were recruited from seven Chinese medical centers within 6 months after experiencing ischemic stroke. Cognitive status was evaluated with a series of brief neuropsychological tests. A subgroup of 439 patients from a single center was followed up for 4-6 years and was eventually reassessed with a cognitive test. The association between Hb and cognitive impairment was analyzed by multivariable Tobit regression and logistic regression. The mean age of the 920 eligible participants at study entry was 42.5 years; 311 (34%) were women, and all participants were Chinese nationals who lived locally. After adjustment for multiple covariables, Hb levels at admission remained positively associated with poststroke Mini-Mental State Examination (MMSE) scores, with a 0.37-point increase in the MMSE score for every 1-standard-deviation increase in the Hb level. Moreover, an optimal Hb level above 15.0 g/dl was proposed for preventing or alleviating the development of poststroke cognitive impairment in men. After 4-6 years of rehabilitation, the baseline Hb still correlated with MMSE scores. A significant interaction was found between baseline Hb and change in MMSE scores over time, with higher baseline Hb levels predicting faster recovery of global cognitive performance (ß, 0.21; 95% confidence interval, 0.03-0.39).These findings warrant further study of anemia as a risk factor for poststroke cognitive impairment.

Structural connectome alterations in patients with disorders of consciousness revealed by 7-tesla magnetic resonance imaging.

Although the functional connectivity of patients with disorders of consciousness (DOC) has been widely examined, less is known about brain white matter connectivity. The aim of this study was to explore structural network alterations for the diagnosis and prognosis of patients with chronic DOC. Eleven DOC patients and 11 sex- and age-matched controls were included in the study. Participants underwent diffusion magnetic resonance imaging (MRI) and T1-weighted structural MRI at 7 tesla (7 T). Graph-theoretical analysis and network-based statistics were used to analyze the group differences. Two patients were scanned twice for a longitudinal study to examine the relationship between connectome metrics and the patients' prognoses. Compared with healthy controls, DOC patients showed significantly elevated transitivity (p < .001), local efficiency (p = .009), and clustering coefficient (p = .039). When comparing the connectome metrics within the three groups (healthy controls, minimally conscious state (MCS), and vegetative state/unresponsive wakefulness syndrome (VS/UWS)), significant group differences were observed in transitivity (p < .001) and local efficiency (p = .031). Significantly increased transitivity was observed in vegetative state/unresponsive wakefulness syndrome compared with minimally conscious state (p = .0217, Bonferroni corrected). Transitivity showed significant negative correlations with the Coma Recovery Scale-Revised score (r = -0.6902, p = .023), consistent with the longitudinal study results. A subnetwork with significantly decreased structural connections was identified using network-based statistical analysis comparing DOC patients with healthy controls, which was mainly located in the frontal cortex, limbic system, and occipital and parietal lobes. This preliminary study suggests that graph theoretical approaches for assessing white matter connectivity may enable various states of DOC to be distinguished. Of the metrics analyzed, transitivity had a critical role in distinguishing the diagnostic groups. Larger cohorts will be necessary to confirm the predictive value of 7 T MRI in the prognosis of DOC patients.

Behavioral and Resting State Functional Connectivity Effects of High Frequency rTMS on Disorders of Consciousness: A Sham-Controlled Study.

Objectives: A combined approach of behavioral characteristics and network properties was applied to explore the effect of repetitive transcranial magnetic stimulation (rTMS) on disorders of consciousness (DOC) and to observe changes in brain network connections before and after the stimulation. Methods: A total of 7 DOC patients and 11 healthy controls were enrolled. The study was designed as a randomized, sham-controlled study. All DOC patients were given 20 Hz rTMS real and sham stimuli to the left M1 region, with each stimulus lasting for 5 consecutive working days and the interval between two stimuli being 1 week. Coma Recovery Scale-Revised (CRS-R) and resting state functional MRI data before and after stimuli were collected. The functional connection (FC) of the default mode network and the frontoparietal network were chosen as the central target to compare differences in network connections between the DOC group and the normal control group. For DOC patients, changes in behavior and brain function before and after real and sham stimuli were also assessed as a group and individually. Results: (1). The overall analyses showed no significant changes of CRS-R scores or brain FC following real or sham rTMS stimuli in the DOC patients. However, real rTMS stimuli tended to enhance the FC of nodes in left lateral parietal cortex (LPC), left inferior temporal cortex (ITC) and right dorsolateral prefrontal cortex (DLPFC). (2). The individual analyses showed one minimally conscious state (MCS) patient presented with a obviously increased CRS-R score following real rTMS stimuli, and a visibly enhanced connectivity was observed in the nodes of left LPC, left ITC and right DLPFC of this patient. Conclusion: Our findings did not provide sufficient evidence of therapeutic effect of 20 Hz rTMS over the left M1 in DOC. However, MCS patients shortly after brain injury may possibly benefit from rTMS. Reconstruction of the left LPC, the left ITC and the right DLPFC may be the brain networking foundation of improvements in consciousness from rTMS.

Blepharospasm with elevated anti-acetylcholine receptor antibody titer.

OBJECTIVES: To determine whether serum levels of anti-acetylcholine receptor antibody (anti-AChR-Abs) are related to clinical parameters of blepharospasm (BSP). METHODS: Eighty-three adults with BSP, 60 outpatients with hemifacial spasm (HFS) and 58 controls were recruited. Personal history, demographic factors, response to botulinum toxin type A (BoNT-A) and other neurological conditions were recorded. Anti-AChR-Abs levels were quantified using an enzyme-linked immunosorbent assay. RESULTS: The anti-AChR Abs levels were 0.237 ± 0.022 optical density units in the BSP group, which was significantly different from the HFS group (0.160 ± 0.064) and control group (0.126 ± 0.038). The anti-AChR Abs level was correlated with age and the duration of response to the BoNT-A injection. CONCLUSION: Patients with BSP had an elevated anti-AChR Abs titer, which suggests that dysimmunity plays a role in the onset of BSP. An increased anti-AChR Abs titer may be a predictor for poor response to BoNT-A in BSP.

Blepharospasm with elevated anti-acetylcholine receptor antibody titer / Blefaroespasmo com título elevado de anticorpos antirreceptores de acetilcolina

ABSTRACT Objective: To determine whether serum levels of anti-acetylcholine receptor antibody (anti-AChR-Abs) are related to clinical parameters of blepharospasm (BSP). Methods: Eighty-three adults with BSP, 60 outpatients with hemifacial spasm (HFS) and 58 controls were recruited. Personal history, demographic factors, response to botulinum toxin type A (BoNT-A) and other neurological conditions were recorded. Anti-AChR-Abs levels were quantified using an enzyme-linked immunosorbent assay. Results: The anti-AChR Abs levels were 0.237 ± 0.022 optical density units in the BSP group, which was significantly different from the HFS group (0.160 ± 0.064) and control group (0.126 ± 0.038). The anti-AChR Abs level was correlated with age and the duration of response to the BoNT-A injection. Conclusion: Patients with BSP had an elevated anti-AChR Abs titer, which suggests that dysimmunity plays a role in the onset of BSP. An increased anti-AChR Abs titer may be a predictor for poor response to BoNT-A in BSP.

RESUMO Objetivo: Determinar se os níveis séricos do anticorpo antirreceptor de acetilcolina (anti-AChR-Abs) estão relacionados aos parâmetros clínicos do blefaroespasmo (BSP). Métodos: Fora recrutados 83 adultos com BSP, 60 pacientes ambulatoriais com espasmo hemifacial (HFS) e 58 controles. Foi aplicado um questionário para registrar história pessoal, fatores demográficos, resposta à toxina botulínica tipo A (BoNT-A) e outras condições neurológicas. Os níveis de anti-AChR-Abs foram quantificados usando um ensaio imunoenzimático. Resultados: O nível de anti-AChR-Abs foi de 0,237 ± 0,022 unidades de densidade óptica (OD) no grupo BSP, significativamente diferente em comparação com o grupo HFS (0,160 ± 0,064) e o grupo controle (0,126 ± 0,038). O nível de anti-AChR-Abs se correlacionou com a idade e a duração da resposta à injeção de BoNT-A. Conclusão: Pacientes com BSP apresentaram títulos elevados de anti-AChR-Abs, o que sugere que a desimunidade desempenha um papel no surgimento de BSP. O aumento do título de anti-AChR-Abs pode ser um preditor de resposta insuficiente à BoNT-A em BSP.

Effects of 20 Hz Repetitive Transcranial Magnetic Stimulation on Disorders of Consciousness: A Resting-State Electroencephalography Study.

Repetitive transcranial magnetic stimulation (rTMS) has been proposed as an experimental approach for the treatment of disorders of consciousness (DOC). To date, there has been little research into the use of rTMS in DOC and the therapeutic effects have been variously documented. This study aimed to examine the effects of 20 Hz rTMS on the electroencephalography (EEG) reactivity and clinical response in patients with DOC and to explore the neuromodulatory effects of high-frequency rTMS. In this randomized, sham-controlled, crossover study, real or sham 20 Hz rTMS was applied to the left primary motor cortex (M1) of patients with DOC for 5 consecutive days. Evaluations were blindly performed at the baseline (T0), immediately after the end of the 5 days of treatment (T1) and 1 week after the treatment (T2) using the JFK coma recovery scale-revised (CRS-R) and resting-state EEG. Only one patient, with a history of 2 months of traumatic brain injury, showed long-lasting (T1, T2) behavioral and neurophysiological modifications after the real rTMS stimulation. The 5 remaining patients presented brain reactivity localized at several electrodes, and the EEG modification was not significant. rTMS stimulation may improve awareness and arousal of DOC. Additionally, EEG represents a potential biomarker for the therapeutic efficacy of rTMS. This trial is registered with (NCT03385278).