Severe Neurological Dysfunction Research Articles

Are carriers unaffected? A literature review of metabolic and health outcomes among genetic carriers of phenylketonuria (PKU).

Phenylketonuria (PKU) is an autosomal recessive genetic condition that results in reduced enzymatic functioning within the phenylalanine hydroxylase (PAH) pathway, which is involved in the metabolism of Phenylalanine (Phe) into Tyrosine (Tyr). Without dietary intervention, individuals with PKU exhibit significantly elevated levels of Phe, which is presumed to cause severe neurological dysfunction and other associated health risks. Carriers of PKU are heterozygotes for a PAH gene mutation and are typically described in the literature as "unaffected." However, decades of existing research challenges this classical thinking and it is plausible that these individuals currently classified as carriers may present with an intermediate phenotype or may be "moderately affected." The purpose of this scoping review was to explore this hypothesis further, by searching for and summarizing existing literature on metabolism and health outcomes among PKU carriers. Preliminary research has suggested that some PKU carriers exhibit reduced PAH enzyme function, and related, elevated circulating Phe levels compared to non-carriers. In addition, Phe dosing trials have further demonstrated that carriers have increased Phe levels and decreased Tyr levels compared to non-carriers. Because of these metabolic perturbations, it is biologically plausible for carriers to experience an intermediate phenotype in terms of metabolic consequences and clinical outcomes. While these outcomes have yet to be thoroughly explored, early research has found associations between PKU carrier status and lower IQs as well as decreased executive functioning, memory, processing speed, and inhibitory control. The PAH pathway is also involved in melanogenesis and research has demonstrated increased melanoma risk among PKU carriers. However, there are many limitations to this research and thus whether or not carriers are clinically impacted cannot yet be conclusively determined. Overall, while preliminary research suggests a possible intermediate phenotype among PKU carriers, the current available research is limited and PKU carriers are still clinically considered "unaffected." This review outlines the current literature while discussing future research endeavours related to the metabolism and health of PKU carriers.

Variant analysis and PGT-M of OTC gene in a Chinese family with ornithine carbamoyltransferase deficiency

BackgroundOrnithine carbamoyltransferase deficiency (OTCD) is a kind of X-linked metabolic disease caused by a deficiency in ornithine transcarbamylase leading to urea cycle disorders. The main reason is that the OTC gene variants lead to the loss or decrease of OTC enzyme function, which hinders the ammonia conversion to urea, resulting in hyperammonemia and severe neurological dysfunction. Here, we studied one Chinese family of three generations who consecutively gave birth to two babies with OTCD. This study aims to explore the pathogenicity of two missense variants in the OTC gene and investigate the application of preimplantation genetic testing for monogenic (PGT-M) for a family troubled by Ornithine carbamoyltransferase deficiency (OTCD).MethodsThe retrospective method was used to classify the pathogenicity of two missense variants in the OTC gene in a family tortured by OTCD. Sanger sequencing was used to validate the variants in the OTC gene, and then the pathogenicity of variants was confirmed through family analysis and bioinformatics software. We used PGT-M to target the OTC gene and select a suitable embryo for transplantation. Prenatal diagnosis was recommended to confirm previous results using Sanger sequencing and karyotyping at an appropriate gestational stage. Tandem mass spectrometry (MS-MS) and gas chromatography-mass spectrometry (GC-MS) were used to detect fetal metabolism after birth. The number of the study cohort is ChiCTR2100053616.ResultsTwo missense variants, c.959G > C (p.Arg320Pro) and c.634G > A (p.Gly212Arg), were validated in the OTC gene in this family. According to the ACMG genetic variation classification criteria, the missense variant c.959G > C can be considered as “pathogenic”, and the missense variant c.634G > A can be regarded as “likely benign.” PGT-M identified a female embryo carrying the heterozygous variant c.959G > C (p.Arg320Pro), which was selected for transplantation. Prenatal diagnosis revealed the same variant in the fetus, and continued pregnancy was recommended. A female baby was born, and her blood amino acid testing and urine organic acid testing were regular. Follow-up was conducted after six months and indicated the girl was healthy.ConclusionOur research first validated the segregation of both c.959G > C and c.634G > A variants in the OTC gene in a Chinese OTCD family. Then, we classified variant c.959G > C as “pathogenic” and variant c.634G > A as “likely benign”, providing corresponding theoretical support for genetic counseling and fertility guidance in this family. PGT-M and prenatal diagnosis were recommended to help the couple receive a female baby successfully with a six-month follow-up.

Risk factors for postoperative late deterioration in patients with spinal dural arteriovenous fistulas.

Approximately 86% of patients with spinal dural arteriovenous fistulas (SDVAFs) exhibit clinical improvement after surgery. However, 12%-55.8% of these patients experience late deterioration (LD) after an initial period of improvement. The risk factors for LD remain unclear. The aim of this study was to explore the risk factors for LD in SDVAF patients. The clinical data of patients who were admitted to two tertiary hospitals between June 2014 and May 2022 were reviewed. Patients were divided into two groups: the LD group and the no LD group. The severity of neurological dysfunction (NDF) was evaluated using the Modified Aminoff and Logue Scale. Univariable and multivariable Cox regression analyses were performed. A total of 105 eligible patients were enrolled, with a mean age of 57.55 ± 9.42 years. The LD group comprised 37 individuals, while the no LD group consisted of 68 individuals. According to the univariable analysis, preoperative NDF severity and treatment strategy were associated with the risk of LD. According to the multivariable analysis, patients who underwent microsurgery (MS) had a lower risk of LD than did those who underwent endovascular treatment (EVT; HR 0.197, 95% CI 0.085-0.457), and patients with severe NDF had a higher risk of LD than did those with mild NDF (HR 3.604, 95% CI 1.226-10.588), whereas the risk of LD in patients with moderate NDF was similar to that of patients with mild NDF (HR 1.352, 95% CI 0.519-3.524). EVT and severe preoperative NDF are independent risk factors for LD.

A novel approach to treating post-stroke depression: administration of Botulinum Toxin A via local facial injection.

Post-stroke depression (PSD) is a frequent complication following a stroke, characterized by prolonged feelings of sadness and loss of interest, which can significantly impede stroke rehabilitation, increase disability, and raise mortality rates. Traditional antidepressants often have significant side effects and poor patient adherence, necessitating the exploration of more suitable treatments for PSD. Previous researchers and our research team have discovered that Botulinum Toxin A (BoNT-A) exhibits antidepressant effects. Therefore, our objective was to assess the efficacy and side effects of BoNT-A treatment in patients with PSD. A total of 71 stroke patients meeting the inclusion criteria were allocated to the two group. 2 cases were excluded due to severe neurological dysfunction that prevented cooperation and 4 cases were lost follow-up. Ultimately, number of participants in the BoNT-A group (n = 32) and Sertraline group (n = 33). Treatment efficacy was evaluated 1, 2, 4, 8 and 12 weeks post-treatment. There were no significant differences in baseline characteristics between the two groups (p > 0.05). Both groups exhibited comparable treatment efficacy, with fewer side effects observed in the BoNT-A group compared to the Sertraline group. BoNT-A therapy demonstrated significant effects as early as the first week (p < 0.05), and by the 12th week, there was a notable decrease in neuropsychological scores, significantly lower than the baseline level. The analysis revealed significant differences in measurements of the Hamilton Depression Scale (HAMD) (F(770) = 12.547, p = 0.000), Hamilton Anxiety Scale (HAMA) (F(951) = 10.422, p = 0.000), Self-Rating Depression Scale (SDS) (F(1385) = 10.607, p = 0.000), and Self-Rating Anxiety Scale (SAS) (F(1482) = 11.491, p = 0.000). BoNT-A treatment effectively reduces depression symptoms in patients with PSD on a continuous basis.

Emodin attenuates hypoxic-ischemic brain damage by inhibiting neuronal apoptosis in neonatal mice

Neonatal hypoxic-ischemic brain damage (HIBD) can lead to mortality and severe neurological dysfunction. Emodin is a natural anthraquinone derivative that is easy to obtain and has good neuroprotective effects. This study aimed to investigate the neuroprotective effect of emodin on neonatal mouse HIBD. The modified Rice–Vannucci method was used to induce HIBD in mouse pups. Eighty postnatal 7-day (P7) C57BL/6 neonatal mice were randomly divided into the sham group (sham), vehicle group (vehicle), and emodin group (emodin). TTC staining and whole-brain morphology were used to evaluate the infarct volume and morphology of the brain tissue. The condition of the neurons was observed through Nissl staining, HE staining, FJC staining, immunofluorescence and Western blot for NeuN, IBA-1, and GFAP. The physiological status of the mice was evaluated using weight measurements. The neural function of the mice was assessed using the negative geotaxis test, righting reflex test, and grip test. TUNEL staining was used to detect apoptosis in brain cells. Finally, Western blot and immunofluorescence were used to detect the expression levels of apoptosis-related proteins, such as P53, cleaved caspase-3, Bax and Bcl-2, in the brain. Experiments have shown that emodin can reduce the cerebral infarct volume, brain oedema, neuronal apoptosis, and degeneration and improve the reconstruction of brain tissue morphology, neuronal morphology, physiological conditions, and neural function. Additionally, emodin inhibited the expression of proapoptotic proteins such as P53, Bax and cleaved caspase-3 and promoted the expression of the antiapoptotic protein Bcl-2. Emodin attenuates HIBD by inhibiting neuronal apoptosis in neonatal mice.

Emergent Management of Central Nervous System Demyelinating Disorders.

This article reviews the various conditions that can present with acute and severe central nervous system demyelination, the broad differential diagnosis of these conditions, the most appropriate diagnostic workup, and the acute treatment regimens to be administered to help achieve the best possible patient outcomes. The discovery of anti-aquaporin 4 (AQP4) antibodies and anti-myelin oligodendrocyte glycoprotein (MOG) antibodies in the past two decades has revolutionized our understanding of acute demyelinating disorders, their evaluation, and their management. Demyelinating disorders comprise a large category of neurologic disorders seen by practicing neurologists. In the majority of cases, patients with these conditions do not require care in an intensive care unit. However, certain disorders may cause severe demyelination that necessitates intensive care unit admission because of numerous simultaneous multifocal lesions, tumefactive lesions, or lesions in certain brain locations that lead to acute severe neurologic dysfunction. Intensive care may be necessary for the management and prevention of complications for patients who have severely altered mental status, rapidly progressive neurologic worsening, elevated intracranial pressure, severe cerebral edema, status epilepticus, or respiratory failure.

Clinical research progress on intrathecal glucocorticoids in the treatment of infections: A review.

In some infectious diseases, pathogenic microorganisms can directly or indirectly cause significant inflammatory reactions in the central nervous system, leading to severe neurological dysfunction, such as suppurative meningitis, tuberculous meningitis, and febrile infections. related epilepsy syndrome, etc. In these diseases, adjuvant administration of glucocorticoids is necessary to inhibit the release of proinflammatory cytokines, and intrathecal administration can deliver the drug more directly to the target. In this article, the authors studied intrathecal glucocorticoids for the treatment of infectious inflammatory reactions in terms of pharmacological effects and mechanisms, pharmacokinetics, clinical application, and safety. The authors concluded that the article could help provide new treatment strategies for infectious diseases.

Nurr1 overexpression in the primary motor cortex alleviates motor dysfunction induced by intracerebral hemorrhage in the striatum in mice

Hemorrhage-induced injury of the corticospinal tract (CST) in the internal capsule (IC) causes severe neurological dysfunction in both human patients and rodent models of intracerebral hemorrhage (ICH). A nuclear receptor Nurr1 (NR4A2) is known to exert anti-inflammatory and neuroprotective effects in several neurological disorders. Previously we showed that Nurr1 ligands prevented CST injury and alleviated neurological deficits after ICH in mice. To prove direct effect of Nurr1 on CST integrity, we examined the effect of Nurr1 overexpression in neurons of the primary motor cortex on pathological consequences of ICH in mice. ICH was induced by intrastriatal injection of collagenase type VII, where hematoma invaded into IC. Neuron-specific overexpression of Nurr1 was induced by microinjection of synapsin I promoter-driven adeno-associated virus (AAV) vector into the primary motor cortex. Nurr1 overexpression significantly alleviated motor dysfunction but showed only modest effect on sensorimotor dysfunction after ICH. Nurr1 overexpression also preserved axonal structures in IC, while having no effect on hematoma-associated inflammatory events, oxidative stress, and neuronal death in the striatum after ICH. Immunostaining revealed that Nurr1 overexpression increased the expression of Ret tyrosine kinase and phosphorylation of Akt and ERK1/2 in neurons in the motor cortex. Moreover, administration of Nurr1 ligands 1,1-bis(3′-indolyl)-1-(p-chlorophenyl)methane or amodiaquine increased phosphorylation levels of Akt and ERK1/2 as well as expression of glial cell line-derived neurotrophic factor and Ret genes in the cerebral cortex. These results suggest that the therapeutic effect of Nurr1 on striatal ICH is attributable to the preservation of CST by acting on cortical neurons.

Targeting of KOR by famotidine promotes OPC maturation differentiation and CNS remyelination via STAT3 signaling pathway

This study aims to identify FDA-approved drugs that can target the kappa-opioid receptor (KOR) for the treatment of demyelinating diseases. Demyelinating diseases are characterized by myelin sheath destruction or formation that results in severe neurological dysfunction. Remission of this disease is largely dependent on the differentiation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes (OLGs) in demyelinating lesions. KOR is an important regulatory protein and drug target for the treatment of demyelinating diseases. However, no drug targeting KOR has been developed due to the long clinical trials for drug discovery. Here, a structure-based virtual screening was applied to identify drugs targeting KOR among 1843 drugs of FDA-approved drug libraries, and famotidine was screen out by its high affinity cooperation with KOR as well as the clinical safety. We discovered that famotidine directly promoted OPC maturation and remyelination using the complementary in vitro and in vivo models. Administration of famotidine was not only effectively enhanced CNS myelinogenesis, but also promoted remyelination. Mechanically speaking, famotidine promoted myelinogenesis or remyelination through KOR/STAT3 signaling pathway. In general, our study provided evidence of new clinical applicability of famotidine for the treatment of demyelinating diseases for which there is currently no effective therapy.

Stereotactic puncture surgery combined with early hyperbaric oxygen therapy may be better for long-term functional recovery in patients with moderate amounts of thalamic-inner capsule region haemorrhage

BackgroundThe prognosis of patients with thalamic hemorrhage is poor, and their long-term neurological impairment is heavy, which seriously affects their work and life.To comparatively analyse the efficacy and prognosis of patients with moderate hemorrhage in the thalamic region who underwent conservative treatment, stereotactic puncture surgery and neuroendoscopic surgery. MethodThis study retrospectively analyzed hospitalization data from 139 adult patients with moderate-volume cerebral hemorrhage in the thalamo-endocapsular region. They were categorized into a stereotactic group (39cases), a neuroendoscopic group (36cases), and a conventional conservative group (64cases). Logistic regression analysis was used to assess risk factors for severe neurological deficits in patients. Multivariate regression modeling was used to compare the correlation of severe neurological deficits among the three groups of patients. ResultsPatients with thalamic moderate-volume cerebral hemorrhage had statistically significantly higher Assessment of Daily Living (ADL) scores in the stereotactic surgery group than in the conservative treatment group and the neuroendoscopic surgery group after 6 months of treatment (p< 0.001).The amount of residual hematoma was significantly lower in the surgery groups than in the conservative treatment group at 3 days, 7 days, and 2 weeks after the onset of the disease (P< 0.001).In multivariate logistic regression analyses, after adjusting for all covariates, the odds ratios for severe neurologic dysfunction in the stereotactic group and the neuroendoscopy group were, respectively, OR: 0.37 (0.12–0.87), P< 0.001 and 0.42 (0.23–1.13), P=0.361). ConclusionIn patients with moderate volume cerebral hemorrhage in the thalamus-inner capsule region cerebral hemorrhage, patients treated with stereotactic surgery combined with early hyperbaric oxygen therapy may have better long-term neurological recovery compared with conservative and neuroendoscopic surgical treatments.

Investigation of the Association between Bilateral Selective Anterograde Cerebral Perfusion and Postoperative Ischemic Stroke in Obese Patients with Emergency Surgery for Acute Type A Aortic Dissection.

Background and objectives: The relationship between cerebral perfusion and new postoperative ischemic stroke in obese patients is not well defined. The aim of this study was to investigate the association between selective bilateral anterograde cerebral perfusion and new postoperative ischemic stroke in obese patients with emergency surgery for acute type A aortic dissection. Materials and methods: A total of 292 patients with emergency surgery for acute type A aortic dissection were included in this study. Patients with hemorrhagic stroke or ischemic stroke with severe neurological dysfunction at admission that were not candidates for surgery; patients who died in the first 48 h after intensive care admission and patients with incomplete medical records were excluded. Results: The mean age was 59.42 ± 10.68 years and the mean Euroscore was 9.12 ± 1.63. Obesity was present in 76.4%, the incidence of new postoperative ischemic stroke was 27.5%, and the postoperative mortality rate was 26.7%. The mean cardiopulmonary bypass time was 206.81 ± 75.48 min, the aortic cross-clamp time was 118.2 ± 46.42 min, and 90% of cases required cerebral perfusion. The mean cerebral perfusion time was 30.8 ± 24.41 min. Obese patients had a higher frequency of in-hospital death (p = 0.009), smoking (p = 0.036), hypertension (p = 0.023), left common carotid artery dissection (p < 0.001), right common carotid artery dissection (p = 0.029), femoral artery cannulation (p = 0.026), aortic root replacement (p = 0.009), aortic valve replacement (p = 0.005) and early reintervention for bleeding (p = 0.004). Using logistic regression, selective bilateral anterograde cerebral perfusion over 40 min in obese patients was independently associated with new postoperative ischemic stroke (OR = 2.35; 95%CI = 1.36-4.86; p = 0.021). Conclusions: A patient-tailored strategy for cerebral perfusion should be considered in obese patients, considering the high atheromatous burden of the supra-aortic vessels in these patients and the potential risk of atheromatous embolization associated with this technique.

Thecaloscopy Reduces the Risk of Recurrent Perineural (Tarlov) Cysts after Microsurgical Resection.

Sacral Tarlov cysts (TCs), often asymptomatic, can cause significant pain and severe neurological dysfunction. Conventional treatments are generally associated with high recurrence and complication rates. Specifically, the substantial recurrence rates, which can reach as high as 50%, significantly impact long-term outcomes. Recent evidence increasingly supports the hypothesis that the formation of Tarlov cysts (TCs) may be associated with inflammatory processes within the nerve root sheath, further exacerbated by elevated cerebrospinal fluid (CSF) pressure. This retrospective study explores thecaloscopy, combined with surgical techniques, as a more effective alternative. We observed a total of 78 patients, 48 of whom underwent endoscopic fenestration of the arachnoid sheath in addition to microsurgical resection of the TC. We found that the fenestration of the arachnoid sheath at the level of lumbosacral spinal nerve root entry led to a significantly decreased risk of developing recurrent TCs (5/48 vs. 9/30). Only one of the patients suffered from a persistent new bladder dysfunction after microsurgical resection. This presented technique provides a promising treatment path for the future management of TCs, offering a safe and more effective treatment option compared to previous methods. Additionally, the advantages of the thecaloscopy provide pathophysiological implications regarding the development of perineural cysts.

KLF5 promotes the ossification process of ligamentum flavum by transcriptionally activating CX43

BackgroundOssification of ligamentum flavum (OLF) is a prevalent degenerative spinal disease, typically causing severe neurological dysfunction. Kruppel-like factor 5 (KLF5) plays an essential role in the regulation of skeletal development. However, the mechanism KLF5 plays in OLF remains unclear, necessitating further investigative studies.MethodsqRT-PCR, immunofluorescent staining and western blot were used to measure the expression of KLF5. Alkaline Phosphatase (ALP) staining, Alizarin red staining (ARS), and the expression of Runt-related transcription factor 2 (RUNX2), osteopontin (OPN), and osteocalcin (OCN) were used to evaluate the osteogenic differentiation. Luciferase activity assay and ChIP-PCR were performed to investigate the molecular mechanisms.ResultsKLF5 was significantly upregulated in OLF fibroblasts in contrast to normal ligamentum flavum (LF) fibroblasts. Silencing KLF5 diminished osteogenic markers and mineralized nodules, while its overexpression had the opposite effect, confirming KLF5’s role in promoting ossification. Moreover, KLF5 promotes the ossification of LF by activating the transcription of Connexin 43 (CX43), and overexpressing CX43 could reverse the suppressive impact of KLF5 knockdown on OLF fibroblasts’ osteogenesis.ConclusionKLF5 promotes the OLF by transcriptionally activating CX43. This finding contributes significantly to our understanding of OLF and may provide new therapeutic targets.

Lrp8 knockout mice fed a selenium-replete diet display subtle deficits in their spatial learning and memory function.

Selenium is an essential trace element that is delivered to the brain by the selenium transport protein selenoprotein P (SEPP1), primarily by binding to its receptor low-density lipoprotein receptor-related protein 8 (LRP8), also known as apolipoprotein E receptor 2 (ApoER2), at the blood-brain barrier. Selenium transport is required for several important brain functions, with transgenic deletion of either Sepp1 or Lrp8 resulting in severe neurological dysfunction and death in mice fed a selenium-deficient diet. Previous studies have reported that although feeding a standard chow diet can prevent these severe deficits, some motor coordination and cognitive dysfunction remain. Importantly, no single study has directly compared the motor and cognitive performance of the Sepp1 and Lrp8 knockout (KO) lines. Here, we report the results of a comprehensive parallel analysis of the motor and spatial learning and memory function of Sepp1 and Lrp8 knockout mice fed a standard mouse chow diet. Our results revealed that Sepp1 knockout mice raised on a selenium-replete diet displayed motor and cognitive function that was indistinguishable from their wild-type littermates. In contrast, we found that although Lrp8-knockout mice fed a selenium-replete diet had normal motor function, their spatial learning and memory showed subtle deficits. We also found that the deficit in baseline adult hippocampal neurogenesis exhibited by Lrp8-deficit mice could not be rescued by dietary selenium supplementation. Taken together, these findings further highlight the importance of selenium transport in maintaining healthy brain function. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Nervonic Acid Synthesis Substrates as Essential Components in Profiled Lipid Supplementation for More Effective Central Nervous System Regeneration.

Central nervous system (CNS) damage leads to severe neurological dysfunction as a result of neuronal cell death and axonal degeneration. As, in the mature CNS, neurons have little ability to regenerate their axons and reconstruct neural loss, demyelination is one of the hallmarks of neurological disorders such as multiple sclerosis (MS). Unfortunately, remyelination, as a regenerative process, is often insufficient to prevent axonal loss and improve neurological deficits after demyelination. Currently, there are still no effective therapeutic tools to restore neurological function, but interestingly, emerging studies prove the beneficial effects of lipid supplementation in a wide variety of pathological processes in the human body. In the future, available lipids with a proven beneficial effect on CNS regeneration could be included in supportive therapy, but this topic still requires further studies. Based on our and others' research, we review the role of exogenous lipids, pointing to substrates that are crucial in the remyelination process but are omitted in available studies, justifying the properly profiled supply of lipids in the human diet as a supportive therapy during CNS regeneration.

Stereotactic Puncture Surgery for the Treatment of Moderate Volume of Thalamus-Internal Capsule Area Hemorrhage: An Analysis of Real-World Data

The efficacy of surgical intervention in ameliorating long-term prognosis for moderate volume of cerebral hemorrhage in the thalamus-internal capsule region remains unsubstantiated by clinical investigations. Consequently, the acquisition of credible evidence is imperative to authenticate the effectiveness of these methodologies. One hundred and three eligible patients with moderate-volume thalamus-internal capsule region cerebral hemorrhage. Twenty-seven pairs of successful matches after using the 1:1 propensity score matching (PSM) method, totaling 54 patients, were analyzed. The short- and long-term treatment outcomes of patients in the stereotactic surgery and conservative treatment groups were compared. The prognosis of the two groups of patients was analyzed by logistic regression analysis and model comparison. The primary outcome of this study was to assess Assessment of daily living(ADL) scores after 6 months of treatment.Based on the analysis of this study,the ADL of the surgical group were significantly higher than those of the conservative treatment group after 6 months of treatment (P< 0.001), and the difference was statistically significant. The amount of residual haematoma was significantly lower in the stereotactic surgery group than in the conservative treatment group at 3 days, 7 days and 2 weeks after the onset of the disease (P< 0.001), and the complication rate was lower than the conservative treatment group (P< 0.05). Univariate logistic regression showed that the risk of severe neurological dysfunction for patients in the surgery group was (OR-0.27, 95% CI: 0.08-0.86, P< 0.05). In multivariate logistic regression analysis, the odds ratio was 0.29 (95% CI: 0.09-0.96, P< 0.05) after adjusting for all covariates. For moderate-volume thalamus-internal capsule region cerebral hemorrhage, stereotactic paracentesis has the advantage of a shorter hospital stay and a lower complication rate than conservative treatment. Moreover, it yields superior outcomes in terms of daily living assessment scores after six months of treatment and enhanced neurological recovery.

Rationale and design of Treatment of Acute Ischaemic Stroke with Edaravone Dexborneol II (TASTE-2): a multicentre randomised controlled trial

BackgroundEdaravone dexborneol is believed to be a novel cytoprotective drug, demonstrating a synergistic combination of antioxidative and anti-inflammatory properties in animal models. The Treatment of Acute Ischaemic Stroke with Edaravone...

The efficacy of virtual reality technology for the postoperative rehabilitation of patients with cervical spondylotic myelopathy (CSM): a study protocol for a randomized controlled trial

BackgroundPatients with cervical spondylosis myelopathy (CSM) may experience severe neurological dysfunction due to untimely spinal cord compression after surgery. These disorders may lead to sensory and motion disorders, causing considerable psychological distress. Recent studies found that virtual reality (VR) technology can be an effective tool for treating spinal cord injuries. Owing to this discovery, we developed an exploratory research project to investigate the impact of this intervention on the postoperative recovery of patients with CSM.MethodsThe purpose of this randomized controlled trial was to evaluate the efficacy of combining VR technology with conventional rehabilitation strategies for the postoperative rehabilitation of patients with CSM. A total of 78 patients will be recruited and randomized to either the conventional rehabilitation group or the group subjected to VR technology combined with conventional rehabilitation strategies. The Japanese Orthopaedic Association (JOA) scale will be the main tool used, and secondary outcomes will be measured via the visual analogue scale (VAS), neck disability index (NDI), and functional MRI (fMRI). The data analysis will identify differences between the intervention and control groups as well as any relationship between the intragroup changes in the functional area of the brain and the subjective scale scores after the intervention.DiscussionThe aim of this trial is to investigate the effect of VR training on the postoperative rehabilitation of patients with CSM after 12 intervention treatments. Positive and negative outcomes will help us better understand the effectiveness of the intervention and its neural impact. If effective, this study could provide new options for the postoperative rehabilitation of patients with CSM.Trial registrationChinese Clinical Trial Registry (ChiCTR2300071544). Registered 17 May 2023, https://www.chictr.org.cn/.

Role of O-GlcNAcylation in Central Nervous System Development and Injuries: A Systematic Review.

The development of central nervous system (CNS) can form perceptual, memory, and cognitive functions, while injuries to CNS often lead to severe neurological dysfunction and even death. As one of the prevalent post-translational modifications (PTMs), O-GlcNAcylation has recently attracted great attentions due to its functions in regulating the activity, subcellular localization, and stability of target proteins. It has been indicated that O-GlcNAcylation could interact with phosphorylation, ubiquitination, and methylation to jointly regulate the function and activity of proteins. Furthermore, a growing number of studies have suggested that O-GlcNAcylation played an important role in the CNS. During development, O-GlcNAcylation participated in the neurogenesis, neuronal development, and neuronal function. In addition, O-GlcNAcylation was involved in the progress of CNS injuries including ischemic stroke, subarachnoid hemorrhage (SAH), and intracerebral hemorrhage (ICH) and played a crucial role in the improvement of brain damage such as attenuating cognitive impairment, inhibiting neuroinflammation, suppressing endoplasmic reticulum (ER) stress, and maintaining blood-brain barrier (BBB) integrity. Therefore, O-GlcNAcylation showed great promise as a potential target in CNS development and injuries. In this article, we presented a review highlighting the role of O-GlcNAcylation in CNS development and injuries. Hence, on the basis of these properties and effects, intervention with O-GlcNAcylation may be developed as therapeutic agents for CNS diseases.

Insulin-like growth factor 1 and its prognostic value in the course of acute ischemic cerebrovascular events.

The aim of the study was to evaluate insulin-like growth factor 1 (IGF-1) as a predictor of the course of an acute cerebral ischemic event (AICE). This polypeptide, by activating receptors that are present in most tissues, including the brain, mediates the anabolic activity of growth hormone (GH) and its impact on growth and maturation processes, as well as organisms' survival time. AICE can occur in the form of a transient ischemic attack (TIA) or an ischemic stroke (IS). The study included 86 participants. The correlation between serum IGF-1 concentration and the clinical status of 56 patients on days 1 and 9 of AICE, as well as risk factors and the course of the disease, were prospectively analyzed. The control group consisted of 30 healthy volunteers. Patients with a minor baseline neurological syndrome had higher serum IGF-1 concentrations than patients with severe baseline neurological dysfunctions. Multidimensional analyses showed that high IGF-1 values independently determined the worse course of the disease, especially in patients with a severe neurological deficit present on the first day of AICE. Our results indicate that the high level of circulating IGF-1 on the first day of AICE is an independent factor determining the unfavorable course of the stroke, and this relationship is proportional to the severity of the baseline neurological deficit. The study also revealed a positive correlation between the decreased plasma IGF-1 concentration on the first day of AICE and the severity of neurological symptoms.