Search Results (1,995)

Background: Parkinson’s disease (PD) often involves autonomic dysfunction, most notably impaired baroreflex sensitivity (BRS), which disrupts cardiovascular homeostasis and contributes to orthostatic hypotension (OH). Pharmacological and invasive treatments, including deep brain stimulation, have yielded inconsistent benefits and carry procedural risks, highlighting the need for safer, more accessible alternatives. In this systematic review, we evaluated non-invasive interventions—spanning somatosensory stimulation, exercise modalities, thermal therapies, and positional strategies—aimed at improving cardiovascular autonomic function in PD. Methods: We searched PubMed, Embase, MEDLINE (Ovid), Google Scholar, ScienceDirect, and Web of Science for studies published between January 2014 and December 2024. Eight original studies (n = 8) including 205 participants met the inclusion criteria for analyzing cardiac sympathovagal balance. Results: Five studies demonstrated significant post-intervention increases in BRS. Most reported favorable shifts in heart rate variability (HRV) and favorable changes in the low-frequency/high-frequency (LF/HF) ratio. Across modalities, systolic blood pressure (SBP) decreased by an average of 5%, and some interventions produced benefits that persisted up to 24 h. Conclusion: Although sample sizes were small and protocols heterogeneous, the collective findings support the potential of non-invasive neuromodulation to enhance BRS and overall cardiovascular regulation in PD. Future research should focus on standardized, higher-intensity or combined protocols with longer follow-up periods to establish durable, clinically meaningful improvements in autonomic function and quality of life for people living with PD. Full article

Brain metastases are a common and deadly complication of many primary tumors. The progression of these tumors is poorly understood, and treatment options are limited. Two important components of tumor growth are hypoxia and angiogenesis. We conducted a review to look at the possibility of a symbiotic relationship between two transcription factors, Hypoxia-Inducible Factor 1α (HIF1α) and Vascular Endothelial Growth Factor (VEGF), and the role they play in metastasis to the brain. We delve further into this possible relationship by examining commonly used chemotherapeutic agents and their targets. Through an extensive literature review, we identified articles that provided evidence of a strong connection between these transcription factors and the growth of brain metastases, many highlighting a symbiotic relationship. Further supporting this, combinations of chemotherapeutic drugs with varying targets have increased the efficacy of treatment. Angiogenesis and hypoxia have long been known to play a large role in the invasion, growth, and poor outcomes of tumors. However, it is not fully understood how these factors influence one another during metastases. While prior studies have investigated the effects separately, we specifically delve into the synergistic and compounding effects that may exist between them. Our findings underscore the need for greater research allocation to investigate the possible symbiotic relationship between angiogenesis and hypoxia in brain metastasis. Full article

Objective: This study aimed to improve the understanding of the lives of patients with chronic neuropathic pain planned for invasive motor cortex stimulation (iMCS) and assess their expectations towards this intervention and its impact. Methods: Semi-structured face-to-face interviews were conducted until saturation of data was reached. Patients were recruited from one university medical center in the Netherlands. All interviews were audio-recorded, transcribed verbatim, and subjected to thematic analysis using iterative and inductive coding by two researchers independently. Results: Fifteen patients were included (11 females; mean age 63 ± 9.4 yrs). Analysis of the coded interviews revealed seven themes: (1) the consequences of living with chronic neuropathic pain; (2) loss of autonomy and performing usual activities; (3) balancing energy and mood; (4) intimacy; (5) feeling understood and accepted; (6) meaning of life; and (7) the expectations of iMCS treatment. Conclusions: This is the first qualitative study that describes the suffering of patients with chronic neuropathic pain, and their expectations prior to invasive brain stimulation. Significant themes in the lives of patients with chronic pain have been brought to light. The findings strengthen communication between physicians, caregivers, and patients. Practice Implications: The insights gathered from the interviews create a structured framework for comprehending the values and expectations of patients living with central pain and reveal the impact of symptoms due to the central pain. This knowledge improves the communication between physicians and caregivers on one side and the patient on the other side. Furthermore, the framework enhances the capacity for shared decision-making, particularly in managing expectations related to iMCS. Full article

Kinesthetic motor imagery (KMI), the mental rehearsal of a motor task without its actual performance, constitutes one of the most common techniques used for brain–computer interface (BCI) control for movement-related tasks. The effect of neural injury on motor cortical activity during execution and imagery remains under investigation in terms of activations, processing of motor onset, and BCI control. The current work aims to conduct a post hoc investigation of the event-related potential (ERP)-based processing of KMI during BCI control of anthropomorphic robotic arms by spinal cord injury (SCI) patients and healthy control participants in a completed clinical trial. For this purpose, we analyzed 14-channel electroencephalography (EEG) data from 10 patients with cervical SCI and 8 healthy individuals, recorded through Emotiv EPOC BCI, as the participants attempted to move anthropomorphic robotic arms using KMI. EEG data were pre-processed by band-pass filtering (8–30 Hz) and independent component analysis (ICA). ERPs were calculated at the sensor space, and analysis of variance (ANOVA) was used to determine potential differences between groups. Our results showed no statistically significant differences between SCI patients and healthy control groups regarding mean amplitude and latency (p < 0.05) across the recorded channels at various time points during stimulus presentation. Notably, no significant differences were observed in ERP components, except for the P200 component at the T8 channel. These findings suggest that brain circuits associated with motor planning and sensorimotor processes are not disrupted due to anatomical damage following SCI. The temporal dynamics of motor-related areas—particularly in channels like F3, FC5, and F7—indicate that essential motor imagery (MI) circuits remain functional. Limitations include the relatively small sample size that may hamper the generalization of our findings, the sensor-space analysis that restricts anatomical specificity and neurophysiological interpretations, and the use of a low-density EEG headset, lacking coverage over key motor regions. Non-invasive EEG-based BCI systems for motor rehabilitation in SCI patients could effectively leverage intact neural circuits to promote neuroplasticity and facilitate motor recovery. Future work should include validation against larger, longitudinal, high-density, source-space EEG datasets. Full article

Background: Traumatic brain injury (TBI) remains a significant contributor to global mortality and long-term neurological disability. Accurate prognostic biomarkers are crucial for enhancing prognostic accuracy and guiding personalized clinical management. Objective: This review assesses the prognostic value of arterial spin labeling (ASL), a non-invasive MRI technique, in adult and pediatric TBI, with a focus on quantitative cerebral blood flow (CBF) and arterial transit time (ATT) measures. A comprehensive literature search was conducted across PubMed, Embase, Scopus, and IEEE databases, including observational studies and clinical trials that applied ASL techniques (pCASL, PASL, VSASL, multi-PLD) in TBI patients with functional or cognitive outcomes, with outcome assessments conducted at least 3 months post-injury. Results: ASL-derived CBF and ATT parameters demonstrate potential as prognostic indicators across both acute and chronic stages of TBI. Hypoperfusion patterns correlate with worse neurocognitive outcomes, while region-specific perfusion alterations are associated with affective symptoms. Multi-delay and velocity-selective ASL sequences enhance diagnostic sensitivity in TBI with heterogeneous perfusion dynamics. Compared to conventional perfusion imaging, ASL provides absolute quantification without contrast agents, making it suitable for repeated monitoring in vulnerable populations. ASL emerges as a promising prognostic biomarker for clinical use in TBI. Conclusion: Integrating ASL into multiparametric models may improve risk stratification and guide individualized therapeutic strategies. Full article

A wide range of strategies have been developed to modulate dysfunctional brain activities. This narrative review provides a comparative analysis of biophysical, genetic, and biological neuromodulation approaches with an emphasis on their known or unknown molecular targets and translational potential. The review incorporates data from both preclinical and clinical studies covering deep brain stimulation, transcranial electrical and magnetic stimulation, focused ultrasound, chemogenetics, optogenetics, magnetogenetics, and toxin-based neuromodulation. Each method was assessed based on specificity, safety, reversibility, and mechanistic clarity. Biophysical methods are widely used in clinical practice but often rely on empirical outcomes due to undefined molecular targets. Genetic tools offer cell-type precision in experimental systems but face translational barriers related to delivery and safety. Biological agents, such as botulinum neurotoxins, provide long-lasting yet reversible inhibition via well-characterized molecular pathways. However, they require stereotaxic injections and remain invasive. To overcome individual limitations and improve targeting, delivery, and efficacy, there is a growing interest in the synthesis of multiple approaches. This review highlights a critical gap in the mechanistic understanding of commonly used methods. Addressing this gap by identifying molecular targets may help to improve therapeutic precision. This concise review could be valuable for researchers looking to enter the evolving field of the neuromodulation of brain function. Full article

Introduction: Despite clinical evidence for efficacy, there has been minimal uptake of transcranial direct current stimulation (tDCS) for musculoskeletal conditions. Thus, our objective was to explore the perceptions and experiences of people living with lower-limb musculoskeletal injury as well as healthy physically active populations and relate this to the usage of tDCS and key aspects of tDCS design that would improve the capacity for implementation. Methods: We conducted a qualitative descriptive study of 16 participants (44% women) using semi-structured focus groups to identify the descriptions and experiences of people living with lower-limb musculoskeletal injury and healthy physically active populations. A thematic template was used to create a coding structure. Codes were then grouped, and key themes were derived from the data. Results: Four primary themes were identified from focus groups. These were (i) the impact of musculoskeletal injuries on health and quality of life, (ii) performance and injury recovery as facilitators to using tDCS, (iii) barriers and facilitators to tCDS application and (iv) design and aesthetic factors for a tDCS device. Discussion: Our qualitative descriptive study identified four themes relevant to the successful implementation of tDCS into rehabilitative and performance practice. To increase the likelihood of successful tDCS implementation, these barriers should be addressed and facilitators promoted. This should include innovative approaches to device application and structure that allow for a stylish, user-friendly design. Full article

Affecting over 50% of stroke patients, dysphagia is still challenging to diagnose and manage due to its complex multifactorial nature and can be the result of disruptions in the coordination of cortical and subcortical neural activity as reflected in electroencephalographic (EEG) signal patterns. Sample Entropy (SampEn), a signal complexity or predictability measure, could serve as a tool to identify any abnormalities associated with dysphagia. The present study aimed to identify quantitative dysphagia biomarkers using SampEn from EEG recordings in post-stroke patients. Sample entropy was calculated in the theta, alpha, and beta bands of EEG recordings in a repetitive swallowing task performed by three groups: 22 stroke patients without dysphagia (controls), 36 stroke patients with dysphagia, and 21 healthy age-matched individuals. Post-stroke patients, both with and without dysphagia, exhibited significant differences in SampEn compared to healthy subjects in the alpha and theta bands, suggesting widespread alterations in brain dynamics. These changes likely reflect impairments in sensorimotor integration and cognitive control mechanisms essential for effective swallowing. A significant cluster was identified in the left parietal region during swallowing in the beta band, where dysphagic patients showed higher entropy compared to healthy individuals and controls. This finding suggests altered neural dynamics in a region crucial for sensorimotor integration, potentially reflecting disrupted cortical coordination associated with dysphagia. The precise quantification of these neurophysiological alterations offers a robust and objective biomarker for diagnosing neurogenic dysphagia and monitoring therapeutic interventions by means of EEG, a non-invasive and cost-efficient technique. Full article

Central nervous system (CNS) disorders present significant therapeutic challenges due to the limited regenerative capacity of neural tissues, resulting in long-term disability for many patients. Consequently, the development of novel therapeutic strategies is urgently warranted. Stem cell therapies show considerable potential for mitigating brain damage and restoring neural connectivity, owing to their multifaceted properties, including anti-apoptotic, anti-inflammatory, neurogenic, and vasculogenic effects. Recent research has also identified exosomes—small vesicles enclosed by a lipid bilayer, secreted by stem cells—as a key mechanism underlying the therapeutic effects of stem cell therapies, and given their enhanced stability and superior blood–brain barrier permeability compared to the stem cells themselves, exosomes have emerged as a promising alternative treatment for CNS disorders. A key challenge in the application of both stem cell and exosome-based therapies for CNS diseases is the method of delivery. Currently, several routes are being investigated, including intracerebral, intrathecal, intravenous, intranasal, and intra-arterial administration. Intracerebral injection can deliver a substantial quantity of stem cells directly to the brain, but it carries the potential risk of inducing additional brain injury. Conversely, intravenous transplantation is minimally invasive but results in limited delivery of cells and exosomes to the brain, which may compromise the therapeutic efficacy. With advancements in catheter technology, intra-arterial administration of stem cells and exosomes has garnered increasing attention as a promising delivery strategy. This approach offers the advantage of delivering a significant number of stem cells and exosomes to the brain while minimizing the risk of additional brain damage. However, the investigation into the therapeutic potential of intra-arterial transplantation for CNS injury is still in its early stages. In this comprehensive review, we aim to summarize both basic and clinical research exploring the intra-arterial administration of stem cells and exosomes for the treatment of CNS diseases. Additionally, we will elucidate the underlying therapeutic mechanisms and provide insights into the future potential of this approach. Full article

Background: Intracerebral hemorrhage (ICH) is a severe form of stroke associated with high morbidity and mortality. While neurosurgical evacuation may offer theoretical benefits, its impact on survival and hospital course remains debated. We aimed to compare the outcomes of surgical versus conservative management in patients with lobar, capsulo-lenticular, and thalamic ICH and to identify factors influencing mortality and the surgical decision. Methods: This single-center, retrospective cohort study included adult patients admitted to the County Clinical Emergency Hospital of Sibiu (2017–2023) with spontaneous supratentorial ICH confirmed via CT (deepest affected structure determining lobar, capsulo-lenticular, or thalamic location). We collected data on demographics, clinical presentation (Glasgow Coma Scale [GCS], anticoagulant use), hematoma characteristics (volume, extension), treatment modality (surgical vs. conservative), and in-hospital outcomes (mortality, length of stay). Statistical analyses included t-tests, χ², correlation tests, and logistic regression to identify independent predictors of mortality and surgery. Results: A total of 445 patients were analyzed: 144 lobar, 150 capsulo-lenticular, and 151 thalamic. Surgical intervention was more common in patients with larger volumes and lower GCS. Overall, in-hospital mortality varied by location, reaching 13% in the lobar group, 20.7% in the capsulo-lenticular group, and 35.1% in the thalamic group. Within each location, surgical intervention did not significantly reduce overall in-hospital mortality despite the more severe baseline presentation in surgical patients. In lobar ICH specifically, no clear survival advantage emerged, although surgery may still benefit those most severely compromised. For capsulo-lenticular hematomas > 30 mL, surgery was associated with lower mortality (39.4% vs. 61.5%). In patients with large lobar ICH, surgical intervention was associated with mortality rates similar to those seen in less severe, conservatively managed cohorts. Multivariable adjustment confirmed GCS and hematoma volume as independent mortality predictors; age and volume predicted the likelihood of surgical intervention. Conclusions: Despite targeting more severe cases, neurosurgical evacuation did not uniformly lower in-hospital mortality. In lobar ICH, surgical patients with larger hematomas (~48 mL) and lower GCS (~11.6) had mortality rates (~13%) comparable to less severe, conservative cohorts, indicating that surgical intervention was associated with similar mortality rates despite higher baseline risk. However, these findings do not establish a causal survival benefit and should be interpreted in the context of non-randomized patient selection. For capsulo-lenticular hematomas > 30 mL, surgery was associated with lower observed mortality (39.4% vs. 61.5%). Thalamic ICH remained most lethal, highlighting the difficulty of deep-brain bleeds and frequent ventricular extension. Across locations, hematoma volume and GCS were the primary outcome predictors, indicating the need for timely intervention, better patient selection, and possibly minimally invasive approaches. Future prospective multicenter research is necessary to refine surgical indications and validate these findings. To our knowledge, this investigation represents the largest and most contemporary single-center cohort study of supratentorial intracerebral hemorrhage conducted in Romania. Full article

Adipose stem cells (ASCs) are a subset of mesenchymal stem cells with validated immunomodulatory and regenerative capabilities that make them attractive tools for treating neurodegenerative disorders, such as multiple sclerosis (MS). Several studies conducted on experimental autoimmune encephalomyelitis (EAE), the animal model of MS, have clearly shown a therapeutic effect of ASCs. However, controversial data on their efficacy were obtained from I- and II-phase clinical trials in MS patients, highlighting standardization issues and limited data on long-term safety. In this context, ASC-derived extracellular vesicles from (ASC-EVs) represent a safer, more reproducible alternative for EAE and MS treatment. Moreover, their physical characteristics lend themselves to a non-invasive, efficient, and easy handling of intranasal delivery. Using an in vitro setting, we first verified ASC-EVs’ ability to cross the human nasal epithelium under an inflammatory milieu. Magnetic resonance corroborated these data in vivo in intranasally treated MOG35-55-induced EAE mice, showing a preferential accumulation of ASC-EVs in brain-inflamed lesions compared to a stochastic distribution in healthy control mice. Moreover, intranasal treatment of ASC-EVs at the EAE onset led to a long-term therapeutic effect using two different experimental protocols. A marked reduction in T cell infiltration, demyelination, axonal damage, and cytokine production were correlated to EAE amelioration in ASC-EV-treated mice compared to control mice, highlighting the immunomodulatory and neuroprotective roles exerted by ASC-EVs during EAE progression. Overall, our study paves the way for promising clinical applications of self-administered ASC-EV intranasal treatment in CNS disorders, including MS. Full article

Background: Botulinum toxin type A (BoNT/A) is widely used in both clinical and aesthetic settings to induce temporary neuromuscular paralysis by inhibiting acetylcholine release. Although generally regarded as safe and effective, complications such as iatrogenic ptosis or facial asymmetry may occur and persist for several weeks or even months, with no standardized method currently available to accelerate recovery. Objective: This article explores the hypothesis that photobiomodulation (PBM)—a non-invasive modality recognized for its neuroregenerative potential—may facilitate the reversal of BoNT/A-induced neuromuscular blockade. Discussion: PBM enhances mitochondrial activity by stimulating cytochrome c oxidase in nerve and muscle tissues, thereby increasing ATP production and modulating intracellular signaling pathways associated with neuroplasticity, cell survival, and synaptogenesis. Preclinical studies have demonstrated that PBM can upregulate neurotrophic factors (e.g., BDNF, NGF), enhance SNAP-25 expression, and promote structural remodeling of neurons in both young and aged brains. These mechanisms are biologically consistent with the regenerative processes required for recovery from BoNT/A-induced effects. While controlled clinical trials for this specific application are currently lacking, anecdotal clinical reports suggest that PBM may accelerate functional recovery in cases of BoNT/A-related complications. Conclusions: Although this approach has not yet been tested in clinical trials, we propose that photobiomodulation may hypothetically serve as a supportive strategy to promote neuromuscular recovery in patients experiencing adverse effects from BoNT/A. This hypothesis is grounded in robust preclinical evidence but requires validation through translational and clinical research. Full article

Background/Objectives: Fatigue and cognitive impairment are common issues for People with Multiple Sclerosis (PwMS), affecting over 80% and 40–65%, respectively. The relationship between these two debilitating conditions is complex, with cognitive deficits exacerbating fatigue and vice versa. This study investigates the effects of a multimodal intervention combining cognitive rehabilitation and neuromodulation to alleviate fatigue and enhance cognitive performance in PwMS. Methods: The research employed multiple baselines across the subjects in a Single-Case Experimental Design (mbSCED) with a cohort of three PwMS diagnosed with Relapsing–Remitting MS. The intervention protocol consisted of a baseline phase followed by a four-week treatment involving transcranial direct current stimulation (tDCS) and cognitive training using RehaCom^® software (version 6.9.0). Fatigue levels were measured using the modified Fatigue Impact Scale (mFIS), while cognitive performance was evaluated through standardized neuropsychological assessments. Results: The multimodal protocol exhibited high feasibility and acceptability, with no dropouts. Individual responsiveness outcomes varied, with two PwMS showing significant decreases in fatigue and improvements in cognitive performance, particularly in the trained domains. Their motor performance and quality of life also improved, suggesting that the treatment had indirect beneficial effects. Conclusions: This study provides preliminary evidence for the potential benefits of integrating neuromodulation and cognitive rehabilitation as a personalized therapeutic strategy for managing fatigue and cognitive impairments in MS. Further research is needed to delineate the specific contributions of each intervention component and establish standardized protocols for clinical implementation. The insights gained may lead to more effective, tailored treatment options for PwMS. Full article

Transcranial direct current stimulation (tDCS) can modulate cortical excitability in a polarity-specific manner, yet identical protocols often produce inconsistent outcomes across sessions or individuals. This narrative review proposes that much of this variability arises from the brain’s intrinsic temporal landscape. Integrating evidence from chronobiology, sleep research, and non-invasive brain stimulation, we argue that tDCS produces reliable, polarity-specific after-effects only within a circadian–homeostatic “window of efficacy”. On the circadian (Process C) axis, intrinsic alertness, membrane depolarisation, and glutamatergic gain rise in the late biological morning and early evening, whereas pre-dawn phases are marked by reduced excitability and heightened inhibition. On the homeostatic (Process S) axis, consolidated sleep renormalises synaptic weights, widening the capacity for further potentiation, whereas prolonged wakefulness saturates plasticity and can even reverse the usual anodal/cathodal polarity rules. Human stimulation studies mirror this two-process fingerprint: sleep deprivation abolishes anodal long-term-potentiation-like effects and converts cathodal inhibition into facilitation, while stimulating at each participant’s chronotype-aligned (phase-aligned) peak time amplifies and prolongs after-effects even under equal sleep pressure. From these observations we derive practical recommendations: (i) schedule excitatory tDCS after restorative sleep and near the individual wake-maintenance zone; (ii) avoid sessions at high sleep pressure or circadian troughs; (iii) log melatonin phase, chronotype, recent sleep and, where feasible, core temperature; and (iv) consider mild pre-heating or time-restricted feeding as physiological primers. By viewing Borbély’s two-process model and allied metabolic clocks as adjustable knobs for plasticity engineering, this review provides a conceptual scaffold for personalised, time-sensitive tDCS protocols that could improve reproducibility in research and therapeutic gain in the clinic. Full article

Due to their clinical heterogeneity, nonspecific symptoms, and the limitations of existing biomarkers and imaging modalities, metabolic brain diseases (MBDs), such as mitochondrial encephalopathies, lysosomal storage disorders, and glucose metabolism syndromes, pose significant diagnostic challenges. This review examines the growing potential of cell-free DNA (cfDNA) derived from cerebrospinal fluid (CSF) epigenetic profiling as a dynamic, cell-type-specific, minimally invasive biomarker approach for MBD diagnosis and monitoring. We review important technological platforms and their use in identifying CNS-specific DNA methylation patterns indicative of neuronal injury, neuroinflammation, and metabolic reprogramming, including cfMeDIP-seq, enzymatic methyl sequencing (EM-seq), and targeted bisulfite sequencing. By synthesizing current findings across disorders such as MELAS, Niemann–Pick disease, Gaucher disease, GLUT1 deficiency syndrome, and diabetes-associated cognitive decline, we highlight the superior diagnostic and prognostic resolution offered by CSF cfDNA methylation signatures relative to conventional CSF markers or neuroimaging. We also address technical limitations, interpretive challenges, and translational barriers to clinical implementation. Ultimately, this review explores CSF cfDNA epigenetic analysis as a liquid biopsy modality. The central objective is to assess whether epigenetic profiling of CSF-derived cfDNA can serve as a reliable and clinically actionable biomarker for improving the diagnosis and longitudinal monitoring of metabolic brain diseases. Full article