Journal of Neurorestoratology最新文献

Objective

This study compared the clinical efficacy and safety of argatroban and alteplase in the treatment of acute cerebral infarction.

Methods

This study retrospectively analyzed 131 patients admitted for acute cerebral infarction within 48 h of onset from 1 December 2018 to 1 May 2021. The patients were divided according to treatment (i.e., the argatroban and alteplase groups). The National Institutes of Health Stroke Scale (NIHSS) scores (before treatment, at 24 h, and at 3, 7, and 14 days),14-day response rate, 3-month modified Rankin Scale score (mRS), activities of daily living (ADL) score, prognosis, and adverse events during treatment were compared.

Results

Sixty-two and 69 patients were enrolled in the alteplase and argatroban groups, respectively, and both had comparable baseline data. The NIHSS scores of the alteplase group decreased significantly before and after treatment (24 h and at 3, 7, and 14 days), whereas those of the alteplase group decreased most rapidly after 24 h of administration. The argatroban group showed no significant changes in NIHSS score in the first 7 days after treatment until day 14, at which it significantly decreased. Statistically significant differences between the two groups were observed in four points (P < 0.05). The 14-day effectivity rate of alteplase was significantly higher than that of argatroban (83.8% vs. 65.2%; χ² = 131; P = 0.001). The 3-month mRS, ADL and pre-treatment comparisons were statistically significant in the two groups (P < 0.05), while the inter-group comparison was not statistically significant (P > 0.05). Furthermore, the outcomes at 3 months after treatment in both groups did not vary significantly (alteplase vs. argatroban: 48/62 vs. 51/69; χ² = 0.217; P = 0.641). Adverse events during treatment included gingival bleeding (two patients), positive fecal occult blood (two patients), and minor intracranial blood ooze (one patient) in the alteplase group, whereas no adverse events (e.g., bleeding and shock) were noted in the argatroban group.

Conclusion

The short-term efficacy of argatroban in improving neurological function in patients with acute cerebral infarction was significantly lower than that of alteplase. However, the long-term efficacy at 3 months of treatment was comparably significant to that of alteplase with fewer adverse events.

Breakthroughs with rapid changes are the themes of the development in Neurorestoratology this year. Given the very difficult circumstances of the persistent COVID-19 pandemic, most of the colleagues in Neurorestoratology have conducted meaningful research and obtained encouraging results, as described in the 2020 Yearbook of Neurorestoratology. Neurorestorative progress during 2021 depicts recent findings on the pathogenesis of neurological diseases, neurorestorative mechanisms and clinical therapeutic achievements. The pathogenesis and risk factors of Alzheimer's disease were parts of the most prominent hot research topics. Yet, it remains controversial whether β-amyloid accumulation and tau protein deposition are the results of, or the reasons for the neurodegenerative processes. Neurogenesis is an important neurorestorative mechanism, however, it is questionable whether neural stem cells are present in the adult humans brain. Thus, neurogenesis may not derive from endogenous neural stem cells in the adult humans. Neurorestorative treatments were important areas of the 2021 research efforts and these therapies are improving the quality of life in patients with neurological diseases. There was major exploration of cell-based therapies for neurological disease and injury. However, unfortunately several multi-center, double-blind or observing-blind, placebo controlled, randomized clinical trials of mesenchymal stromal cells or products of mesenchymal stem cells failed to show positive results in ischemic stroke when employed in the sub-acute or recovery phases as there were no appreciable differences in the quality of life as compared with controls. Excitingly, increased numbers of clinical investigations of brain–computer interface (BCI) were reported that showed benefits for patients with neurological deficits. In pharmaceutical neurorestorative therapies, Aducanumab (Aduhelm) and Sodium Oligomannate are approved respectively by the United States Food and Drug Administration (USFDA) and the China National Medical Products Administration (NMPA) to treat patients with mild-to-moderate Alzheimer's disease. Although, the decisions to approve these drugs are highly contentious in the medical and scientific community because of the contradictory findings or other problems associated with the drug usage. We believe that repeating low-level evidence studies that showed negative results or scanty evidences in randomized control trials is of little significance. However, we strongly recommend conducting multi-center, double-blind, placebo controlled, randomized clinical trials for promising innovative therapeutic methods to facilitate their possible clinical translation.

Cell therapy has been shown to be a crucial clinical therapeutic option for central nervous system diseases or damage. Promoting standardization of clinical cell therapy procedures is essential for professional associations devoted to cell therapy. The International Association of Neurorestoratology (IANR) and the Chinese Association of Neurorestoratology (CANR; Preparatory) collaborated to release Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017) in 2018. Due to recent advances and achievements in clinical cell therapy worldwide in recent years, IANR and CANR have renewed and updated the guidelines. Except for the requirements of equipment, personnel, and ethics, these revised guidelines include cell type nomenclature, cell quality control, cell types in clinical application, minimal suggested cellular doses, patient-informed consent, indications and contraindications for undergoing cell therapy, documentation of procedure and therapy, safety evaluation, efficacy evaluation, the policy of repeated treatments, do not charge patients for unproven therapies, basic principles of cell therapy, and publishing responsibility. IANR/CANR recommends that all clinical practitioners follow these cellular therapy guidelines. These guidelines provide references of better cell types, doses, routes, and therapeutic timing windows in different diseases.

So far many people still believe that there is a lack of effective drugs or strategies to restore the dysfunction and/or the damaged structure of refractory neurological diseases. However, neurorestorative treatments are being tried to change the state. Transplanted neural progenitor/precursor cells (NPCs) as a novel therapy strategy played an important role in promoting neurological function restoration. Evidence demonstrated that the positive effects of grafted NPCs were mediated mainly by the releasing paracrine factors, especially exosomes, which were derived from NPCs. Exosomes are important paracrine molecules involved in cellular functions and cell-cell communications. This standard was set up by the Chinese Association of Neurorestoratology (CANR; Preparatory) and the China Committee of International Association of Neurorestoratology (IANR-China Committee) to provide rational guidance for technological transformation and clinical applications. In this standard, we highlighted the nature and features of NPC-derived exosomes, aimed to integrate the production, education, and research on the clinical-grade NPC-derived exosomes, promote the relevant standards and regulations established by the government and promote to make the world professional standards.

The cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) is associated with multiple signaling pathways. The signaling pathways leading to epilepsy have been extensively studied and include the Ca²⁺/CaMKiV/CREB pathway, the MAPK/CREB pathway, and the PI3K/Akt/CREB pathway. The regulation of transcription in cells requires CREB phosphorylation and dephosphorylation. Based on a review of the relevant literature, we found that increasing evidence demonstrates that drug-resistant epilepsy might be closely related to the upregulation and phosphorylation of CREB. Previous studies have shown that the mechanisms of epileptogenesis are associated with the over-excitability and sudden synchronous discharge of neurons. In turn, we have learned that inflammation produces proinflammatory factors that damage the blood–brain barrier and activate microglia (MG) and astrocytes (AS). Activated MG and AS not only play neuroprotective roles, but also cause neuroinflammation, which in turn damages nerve cells through CREB-related signaling pathways, leading to reduced effectiveness of antiepileptic drugs and, ultimately, to drug resistance in patients with epilepsy. Therefore, we hypothesized that the formation of drug-resistant epilepsy is related to the regulation of CREB activation or phosphorylation in glial cells activated by chronic inflammation.

Acetylcholine (ACh) is one of the most important neurotransmitters in the central cholinergic system; it specifically binds to muscarinic and nicotinic receptors and is degraded by acetylcholinesterase (AChE). ACh plays a crucial role in learning and memory. It is generally believed that, in the central nervous system, ACh promotes the conduction of brain nerves and accelerates information transmission. Besides, increasing central ACh levels can enhance memory ability and comprehensively improve brain function. Thus, AChE inhibitors (AChEI), which inhibit the degradation of ACh by AChE, have been used to treat Alzheimer's disease (AD) and Parkinson's disease dementia (PDD). However, recent studies have shown that excessive ACh in the central nervous system impairs learning and memory. Here we review the roles of ACh in learning and memory; we focus on the adverse effects of excessive ACh, the possible mechanisms, and the bidirectional role of ACh in the pathology and cure of AD and PDD. We conclude that the timing and dose of ACh administration should be carefully prescreened when using it to alleviate learning and memory in dementia patients.

Objective

To study the dose-response relationship between different treatment parameters of extracorporeal shock wave (ESW) and their effects on spasticity in children with cerebral palsy by the orthogonal design and to select the best parameter scheme for clinical efficacy.

Methods

From March 2020 to December 2020, 80 children with spastic cerebral palsy were randomly divided into eight groups of 10 cases. Patients in each group received ESW with varying wave intensities (A), wave frequencies (B), number of shocks (C), and treatment frequencies (D), which were determined by a 4-factor-2-level orthogonal array design. Modified Ashworth Scale (MAS) and GMFM were scored before and after the study, and the difference during the study was calculated to evaluate the performance of each group.

Results

The R-value of ΔMAS was RA > RD > RC > RB and that of ΔGMFM was RA > RC > RD > RB. The influence of the two levels for each factor was A1 > A2, B2 > B1, C2 > C1, D2 > D1. By the analysis of variance, the differences in factors A, C, and D were statistically significant (P < 0.05). The optimal combination of ESW treatment parameters for the spasticity of cerebral palsy was 1.5 bar, 10 Hz, 2000 times, and twice a week.

Conclusion

ESW is an effective treatment for spastic cerebral palsy and is worthy of clinical application.

Brain trauma or traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide. Along with the conventional therapeutic strategies, neurorestorative treatments for TBI have been developed in recent decades. However, missing standards and guidelines has become a growing issue both in clinical practice and fundamental research. Consequently, the Chinese Association of Neurorestoratology (Preparatory; CANR) and the China Committee of International Association of Neurorestoratology (IANR-China Committee) have reached a consensus to form and approve the Guideline of Clinical Neurorestorative Treatment for Brain Trauma. This guideline addresses the common issues in the evaluation and therapies of TBI patients within the scope of Neurorestoratology, offers recommendations based on state-of-art clinical evidences, and covers cell therapies, neural stimulation therapies, and pharmaceutical therapies. Hopefully, this guideline may provide references to clinical professionals during diagnosis and treatment, maximizing the neurorestorative therapeutic efficacy.

We present the case of a novel homozygous nonsense (c.4846C > T [p.R1616X]) mutation in the VPS13B in a Chinese boy with the primary symptoms of Cohen syndrome. This case presented with manifestations consistent with Cohen syndrome, including developmental delay, microcephaly, typical facial features, short stature, muscle hypotonia, neutropenia, and abnormal dental development; however, the patient did not have the typical findings of obesity, myopia, progressive retinal dystrophy, or epilepsy. The patient had a homozygous nonsense mutation (NM_017890: c.4846C > T [p.R1616X]). His brother, sister, and parents are heterozygous for the mutation. This locus variation has not been previously reported in Chinese children. Different mutation sites have different phenotypes. Cohen syndrome caused by a homozygous nonsense mutation of the VPS13B c.4846C > T (p.R1616X) does not present with obesity, ophthalmic abnormalities, or epilepsy, but has abnormal dental development. This may be related to the premature termination of peptide synthesis caused by nonsense mutations at this site.

Spinal cord injury (SCI) is catastrophic damage for patients, their family, and society. Researchers and clinicians have been trying to find neurorestorative methods to recover their injured functions and structures. Cell therapy is one of the effective therapeutic strategies for SCI. And it can partially restore their neurological functions, which are once thought as permanent neurological deficits. Currently, cells being used therapeutically in clinic include olfactory ensheathing cells (OECs), mononuclear cells (MNCs), mesenchymal stromal cells (MSCs), Schwann cells, and hematopoietic stem cells, cell products differentiated from embryonic stem cells, mesenchymal stem cells, induced pluripotent stem cells, and neural stem cells as well as other kinds of cells. Real world data from these cell therapies showed some benefits in some patients with SCI. Due to being affected by many factors, the therapeutic results of some kinds of cells are contradictory and it is hard to compare effects among different types of cells. According to the data of cell therapies, OEC, MNC and MSC transplantation are applied for patients in majority percentage of cases, and OEC transplantation had a higher percentage of benefits. In next step, under the unified standard of cell preparation and quality control as well as the guidelines of clinical cell application, each kind of cells including OECs should be studied using prospective, multicenter, double-blind or observing-blind, placebo-control, randomized studies for SCI patients with different level of injury and chronicity.