A systematic review on the outcome of intramedullary spinal cord cavernous malformations.

PURPOSE: This study aimed to investigate the neurological outcome, trends and sequelae following surgical or conservative treatment of intramedullary spinal cord cavernous malformations (ISCCMs). METHODS: A systematic review was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The primary outcome measure was the change in the neurological status after surgery or conservative management. A logistic regression analysis investigating prognostic factors related to outcome was also performed. RESULTS: Twenty-one studies with 1091 patients in total were included, of which 1005 (92.1%) underwent surgical resection and 86 (7.9%) were treated conservatively. Gross total resection was achieved in 95.7% of the patients and partial resection in 4.3%. Most lesions (60.2%) were located in the thoracic spine and presented with motor (60.4%) and sensory deficits (59.7%). In the long term, surgical treatment resulted in an improved neurological status in 36.9% of the patients, in 55.8% it remained stable, and in 7.3% it deteriorated compared to the preoperative state. In the conservative cohort, 21.7% improved, 69.6% remained stable, and 8.7% deteriorated. Solitary lesions, duration of preoperative symptoms less than 3 months as well as an improved post-operative neurological status were predictors of a favourable long-term outcome. CONCLUSIONS: Whenever feasible, symptomatic patients with ISCCM are recommended to undergo surgery within 3 months from symptom onset. Absence of multiple lesions and, most importantly, post-operative symptom improvement foresee a favourable long-term outcome. Further research is warranted to discern the role of conservative treatment in symptomatic patients.

Spinal cord stimulation in the treatment of peripheral vascular disease: a systematic review - revival of a promising therapeutic option?

INTRODUCTION: Peripheral vascular disease (PVD) is caused by a blood circulation disorder of the arteries and Critical Limb Ischemia (CLI) is the advanced state of PVD. For patients with surgically non-reconstructable CLI, Spinal Cord Stimulation (SCS) appears to be an alternative therapeutic option. OBJECTIVE: The aim of our study was to investigate the efficacy of SCS in non-reconstructable CLI compared with the conservative treatment and re-appraise the existing literature in light of the recent advances in neuromodulation. METHODS: We conducted a systematic review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, using electronic databases and reference lists for article retrieval. RESULTS: A total of 404 records were identified and finally 6 randomised controlled trials (RCTs), a Cochrane review and a meta-analysis were included in our systematic review. The studies assessed the efficacy of tonic SCS in the treatment of patients with non-reconstructable CLI compared with the conservative treatment. There is moderate to high quality evidence suggesting, that tonic SCS has beneficial effects for patients suffering from non-reconstructable CLI in terms of limb salvage, pain relief, clinical improvement and quality of life. The contradictory conclusions of the two meta-analyses regarding the efficacy of SCS for limb salvage at 12 months refer rather to the magnitude of the beneficial effect than to the effect itself. So far, the current literature provides evidence about the traditional tonic SCS but there is a lack of studies investigating the efficacy of new waveforms in the treatment of non-reconstructable CLI. CONCLUSION: SCS represents an alternative for PVD patients with non-reconstructable CLI and the existing literature provides encouraging clinical results, that should not be neglected. Instead, they should be re-appraised in light of the recent advances in neuromodulation with the emergence of novel waveform technologies and neuromodulation targets.

Motor and Non-motor Outcomes of Deep Brain Stimulation across the Genetic Panorama of Parkinson's Disease: A Multi-Scale Meta-Analysis.

BACKGROUND: In the era of modern medicine, where high-throughput sequencing techniques are readily available, it is desirable to elucidate the role of genetic background in patients with Parkinson's Disease (PD) undergoing Deep Brain Stimulation (DBS). Genetic stratification of PD patients undergoing DBS may assist in patient selection and prediction of clinical outcomes and complement existing selection procedures such as levodopa challenge testing. OBJECTIVE: To capture a broad spectrum of motor and non-motor DBS outcomes in genetic PD patients with data from the recently updated literature. METHODS: A multi-scale meta-analysis with 380 genetic PD cases was conducted using the Cochrane Review Manager, JASP software and R. RESULTS: This meta-analysis revealed that overall, patients with genetic PD are good candidates for DBS but the outcomes might differ depending on the presence of specific mutations. PRKN carriers benefited the most regarding motor function, daily dose medication and motor complications. However, GBA carriers appeared to be more prone to cognitive decline after subthalamic nucleus DBS accompanied by a low quality of life with variable severity depending on genetic variants and concomitant alterations in other genes. Apart from GBA, cognitive worsening was also observed in SNCA carriers. Pre-operative levodopa responsiveness and a younger age of onset are associated with a favorable motor outcome. CONCLUSION: A personalized approach with a variant-based risk stratification within the emerging field of surgicogenomics is needed. Integration of polygenic risk scores in clinical-decision making should be encouraged.

Blood-Brain Barrier-Targeting Nanoparticles: Biomaterial Properties and Biomedical Applications in Translational Neuroscience.

Overcoming the blood-brain barrier (BBB) remains a significant hurdle in effective drug delivery to the brain. While the BBB serves as a crucial protective barrier, it poses challenges in delivering therapeutic agents to their intended targets within the brain parenchyma. To enhance drug delivery for the treatment of neurological diseases, several delivery technologies to circumvent the BBB have been developed in the last few years. Among them, nanoparticles (NPs) are one of the most versatile and promising tools. Here, we summarize the characteristics of NPs that facilitate BBB penetration, including their size, shape, chemical composition, surface charge, and importantly, their conjugation with various biological or synthetic molecules such as glucose, transferrin, insulin, polyethylene glycol, peptides, and aptamers. Additionally, we discuss the coating of NPs with surfactants. A comprehensive overview of the common in vitro and in vivo models of the BBB for NP penetration studies is also provided. The discussion extends to discussing BBB impairment under pathological conditions and leveraging BBB alterations under pathological conditions to enhance drug delivery. Emphasizing the need for future studies to uncover the inherent therapeutic properties of NPs, the review advocates for their role beyond delivery systems and calls for efforts translating NPs to the clinic as therapeutics. Overall, NPs stand out as a highly promising therapeutic strategy for precise BBB targeting and drug delivery in neurological disorders.

A Bayesian Network Meta-Analysis and Systematic Review of Guidance Techniques in Botulinum Toxin Injections and Their Hierarchy in the Treatment of Limb Spasticity.

Accurate targeting of overactive muscles is fundamental for successful botulinum neurotoxin (BoNT) injections in the treatment of spasticity. The necessity of instrumented guidance and the superiority of one or more guidance techniques are ambiguous. Here, we sought to investigate if guided BoNT injections lead to a better clinical outcome in adults with limb spasticity compared to non-guided injections. We also aimed to elucidate the hierarchy of common guidance techniques including electromyography, electrostimulation, manual needle placement and ultrasound. To this end, we conducted a Bayesian network meta-analysis and systematic review with 245 patients using the MetaInsight software, R and the Cochrane Review Manager. Our study provided, for the first time, quantitative evidence supporting the superiority of guided BoNT injections over the non-guided ones. The hierarchy comprised ultrasound on the first level, electrostimulation on the second, electromyography on the third and manual needle placement on the last level. The difference between ultrasound and electrostimulation was minor and, thus, appropriate contextualization is essential for decision making. Taken together, guided BoNT injections based on ultrasound and electrostimulation performed by experienced practitioners lead to a better clinical outcome within the first month post-injection in adults with limb spasticity. In the present study, ultrasound performed slightly better, but large-scale trials should shed more light on which modality is superior.

A neurodevelopmental epigenetic programme mediated by SMARCD3-DAB1-Reelin signalling is hijacked to promote medulloblastoma metastasis.

How abnormal neurodevelopment relates to the tumour aggressiveness of medulloblastoma (MB), the most common type of embryonal tumour, remains elusive. Here we uncover a neurodevelopmental epigenomic programme that is hijacked to induce MB metastatic dissemination. Unsupervised analyses of integrated publicly available datasets with our newly generated data reveal that SMARCD3 (also known as BAF60C) regulates Disabled 1 (DAB1)-mediated Reelin signalling in Purkinje cell migration and MB metastasis by orchestrating cis-regulatory elements at the DAB1 locus. We further identify that a core set of transcription factors, enhancer of zeste homologue 2 (EZH2) and nuclear factor I X (NFIX), coordinates with the cis-regulatory elements at the SMARCD3 locus to form a chromatin hub to control SMARCD3 expression in the developing cerebellum and in metastatic MB. Increased SMARCD3 expression activates Reelin-DAB1-mediated Src kinase signalling, which results in a MB response to Src inhibition. These data deepen our understanding of how neurodevelopmental programming influences disease progression and provide a potential therapeutic option for patients with MB.

The positive dimension of schizotypy is associated with a reduced attenuation and precision of self-generated touch.

The brain predicts the sensory consequences of our movements and uses these predictions to attenuate the perception of self-generated sensations. Accordingly, self-generated touch feels weaker than an externally generated touch of identical intensity. In schizophrenia, this somatosensory attenuation is substantially reduced, suggesting that patients with positive symptoms fail to accurately predict and process self-generated touch. If an impaired prediction underlies the positive symptoms of schizophrenia, then a similar impairment should exist in healthy nonclinical individuals with high positive schizotypal traits. One hundred healthy participants (53 female), assessed for schizotypal traits, underwent a well-established psychophysics force discrimination task to quantify how they perceived self-generated and externally generated touch. The perceived intensity of tactile stimuli delivered to their left index finger (magnitude) and the ability to discriminate the stimuli (precision) was measured. We observed that higher positive schizotypal traits were associated with reduced somatosensory attenuation and poorer somatosensory precision of self-generated touch, both when treating schizotypy as a continuous or categorical variable. These effects were specific to positive schizotypy and were not observed for the negative or disorganized dimensions of schizotypy. The results suggest that positive schizotypal traits are associated with a reduced ability to predict and process self-generated touch. Given that the positive dimension of schizotypy represents the analogue of positive psychotic symptoms of schizophrenia, deficits in processing self-generated tactile information could indicate increased liability to schizophrenia.

Motor Evoked Potential Warning Criteria in Supratentorial Surgery: A Scoping Review.

During intraoperative monitoring of motor evoked potentials (MEP), heterogeneity across studies in terms of study populations, intraoperative settings, applied warning criteria, and outcome reporting exists. A scoping review of MEP warning criteria in supratentorial surgery was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Sixty-eight studies fulfilled the eligibility criteria. The most commonly used alarm criteria were MEP signal loss, which was always a major warning sign, followed by amplitude reduction and threshold elevation. Irreversible MEP alterations were associated with a higher number of transient and persisting motor deficits compared with the reversible changes. In almost all studies, specificity and Negative Predictive Value (NPV) were high, while in most of them, sensitivity and Positive Predictive Value (PPV) were rather low or modest. Thus, the absence of an irreversible alteration may reassure the neurosurgeon that the patient will not suffer a motor deficit in the short-term and long-term follow-up. Further, MEPs perform well as surrogate markers, and reversible MEP deteriorations after successful intervention indicate motor function preservation postoperatively. However, in future studies, a consensus regarding the definitions of MEP alteration, critical duration of alterations, and outcome reporting should be determined.

Role of metabolic dysfunction and inflammation along the liver-brain axis in animal models with obesity-induced neurodegeneration.

The interaction between metabolic dysfunction and inflammation is central to the development of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Obesity-related conditions like type 2 diabetes and non-alcoholic fatty liver disease exacerbate this relationship. Peripheral lipid accumulation, particularly in the liver, initiates a cascade of inflammatory processes that extend to the brain, influencing critical metabolic regulatory regions. Ceramide and palmitate, key lipid components, along with lipid transporters lipocalin-2 and apolipoprotein E, contribute to neuroinflammation by disrupting blood-brain barrier integrity and promoting gliosis. Peripheral insulin resistance further exacerbates brain insulin resistance and neuroinflammation. Preclinical interventions targeting peripheral lipid metabolism and insulin signaling pathways have shown promise in reducing neuroinflammation in animal models. However, translating these findings to clinical practice requires further investigation into human subjects. In conclusion, metabolic dysfunction, peripheral inflammation, and insulin resistance are integral to neuroinflammation and neurodegeneration. Understanding these complex mechanisms holds potential for identifying novel therapeutic targets and improving outcomes for neurodegenerative diseases.