[Thinking on the classification of non-invasive brain stimulation as neuromodulation technique].

Neuromodulation techniques have gradually evolved from electrical or chemical methods to various physical stimulation techniques including electricity, magnetism, sound, light, heat, and more. However, the clinical efficacy and mechanisms of each stimulation technique or paradigm vary greatly. To facilitate the understanding of the therapeutic effects and mechanisms of different neuromodulation techniques, combined with current clinical practice, the author takes the classification of non-invasive transcranial electrical stimulation as an example and proposes the idea of using energy magnitude as the primary classification and different media/stimulation routes as the secondary classification. This classification emphasizes the energy essence of various physical stimuli, followed by the transmission carriers of physical stimuli. This classification method helps to guide and design neuromodulation paradigms for different target symptoms in various brain disorders, which is beneficial for better serving clinical diagnosis and treatment. The Expert Forum also discusses the advantages and disadvantages of various neuromodulation technologies and their clinical applications.

Co-transplantation of autologous treg cells: A groundbreaking cell therapy for brain diseases.

Cell therapy and regenerative medicine have made remarkable progress in treating neurodegenerative disorders. Induced pluripotent stem cells (iPSCs) offer a promising source for cell replacement therapies, but their practical application faces challenges due to poor survival and integration after transplantation. Park et al. propose a novel therapeutic strategy involving the co-transplantation of regulatory T cells (Tregs) and iPSC-derived dopamine neurons. This combined approach enhances the survival of transplanted cells and protects against neuroinflammation-induced damage. In PD animal models, the co-transplantation approach significantly suppressed the host immune response, resulting in improved behavioral recovery. Additionally, Tregs demonstrate acute neuroprotection and contribute to delayed neuro-restoration in ischemic stroke. This combined approach of cell therapy with immunomodulation offers a promising avenue for advancing our understanding of neurological diseases and promoting the development of novel treatments.

NeuroDots: From Single-Target to Brain-Network Modulation: Why and What Is Needed?

OBJECTIVES: Current techniques in brain stimulation are still largely based on a phrenologic approach that a single brain target can treat a brain disorder. Nevertheless, meta-analyses of brain implants indicate an overall success rate of 50% improvement in 50% of patients, irrespective of the brain-related disorder. Thus, there is still a large margin for improvement. The goal of this manuscript is to 1) develop a general theoretical framework of brain functioning that is amenable to surgical neuromodulation, and 2) describe the engineering requirements of the next generation of implantable brain stimulators that follow from this theoretic model. MATERIALS AND METHODS: A neuroscience and engineering literature review was performed to develop a universal theoretical model of brain functioning and dysfunctioning amenable to surgical neuromodulation. RESULTS: Even though a single target can modulate an entire network, research in network science reveals that many brain disorders are the consequence of maladaptive interactions among multiple networks rather than a single network. Consequently, targeting the main connector hubs of those multiple interacting networks involved in a brain disorder is theoretically more beneficial. We, thus, envision next-generation network implants that will rely on distributed, multisite neuromodulation targeting correlated and anticorrelated interacting brain networks, juxtaposing alternative implant configurations, and finally providing solid recommendations for the realization of such implants. In doing so, this study pinpoints the potential shortcomings of other similar efforts in the field, which somehow fall short of the requirements. CONCLUSION: The concept of network stimulation holds great promise as a universal approach for treating neurologic and psychiatric disorders.

Maternal levels of care during pregnancy influence labor and delivery outcomes - present practices and future priorities.

Neonatal encephalopathy (NE) is a diagnosis that is usually unexpected. Though there are many risk factors for the condition and multiple theories as to its genesis, the majority of cases cannot be predicted prior to the occurrence of the clinical syndrome. Indeed, it is common for a pregnant person to have multiple risk factors and a completely healthy child. Conversely, people with seemingly no risk factors may go on to have a profoundly affected child. In this synopsis we review risk factors, potential mechanisms for encephalopathy, the complicated issue of choosing which morbidity to take on and how the maternal level of care may influence outcomes. The reader should be able to better understand the limitations of current testing and the profound levels of maternal intervention that have been undertaken to prevent or mitigate the rare, but devastating occurrence of NE. Further, we suggest candidate future approaches to prevent the occurrence, and decrease the severity of NE. Any future improvements in the NE syndrome cannot be achieved via obstetric intervention and management alone or conversely, by improvements in treatments offered post-birth. Multidisciplinary approaches that encompass prepregnancy health, pregnancy care, intrapartum management and postpartum care will be necessary.

Transplantation-Associated Altered Mentation and Encephalopathy: A New Classification for Acute Neurocognitive Changes Associated with Hematopoietic Cell Transplantation from the ASTCT Committee on Practice Guidelines.

Acute encephalopathy, manifesting clinically as delirium, is a common but often unrecognized complication of hematopoietic cell transplantation (HCT). Delirium can occur in patients of any age and is observed after autologous or allogeneic HCT. Although delirium has been studied primarily during initial HCT hospitalizations in recipients of myeloablative conditioning, recent investigations have identified delirium later post-transplantation and in recipients of reduced-intensity conditioning. Acute encephalopathy can be driven by infectious complications, medications, tissue damage, and/or organ dysfunction. Altered consciousness, either mild or profound, is often its only clinical manifestation. Identifying delirium is essential to overall HCT care, because patients who experience delirium have longer hospitalization and recovery times and are at risk for other poor post-HCT outcomes. Given the critical nature of this common complication and the ongoing expansion of HCT for more vulnerable populations, the American Society of Transplantation and Cellular Therapy (ASTCT) recommends intensifying research into post-HCT cognitive changes and establishing standardized definitions that encompass the full spectrum of altered consciousness for clinical care purposes and to provide benchmark endpoints for future research studies. To capture a range of acute neurocognitive changes specifically found in HCT patients (often referred to as acute encephalopathy), the ASTCT proposes a new diagnosis, transplantation-associated altered mentation and encephalopathy (TAME). The TAME diagnosis includes HCT patients who meet Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for delirium and those with acute neurocognitive changes who do not meet all the DSM-5 criteria for delirium (subsyndromal delirium). Early TAME is defined as occurring during conditioning or ≤100 days post-HCT, whereas late TAME occurs >100 days post-HCT in patients with additional HCT-related complications. This manuscript establishes clear diagnostic criteria and discusses factors that can potentially impact the development of TAME, as well as the workup and management of TAME.

Disease spectrum and strategy of acupuncture and moxibustion in treatment of encephalopathy. / è„‘ç— é’ˆç¸æ²»ç–—çš„ç— è°±ä¸Žç­–ç•¥æ€è€ƒ.

The paper presents the summary of the spectrum of encephalopathy treated with acupuncture and moxibustion and the analysis on the existing questions in its clinical research, and proposes the potential strategies on treatment of encephalopathy with acupuncture and moxibustion. The spectrum of encephalopathy includes 23 diseases of central nervous system (superspinal center) and 33 kinds of mental and behavioral disorders. There are three problems in clinical research of acupuncture and moxibustion for encephalopathy, i.e. lack of high-quality clinical evidences, inadequate support from theoretic study of TCM and limited study on the rules of treatment. Hence, the author proposes five strategies on the treatment of encephalopathy with acupuncture and moxibustion, i.e. ① stimulating the peripheral nerve trunk associated with brain dysfunction, triggering the interaction between peripheral and central nerves and emphasizing the autonomic rehabilitation training to promote the reorganization of brain function; ② improving the cerebral circulation and metabolism by stimulating the trigeminal nerve and sphenopalatine ganglion; ③ stimulating the sites with high-dense distribution of peripheral nerve endings and the large projection area in the somatosensory region of the brain to induce strong brain responses, which may adjust the abnormal operation of the default mode network in the resting state; ④ stimulating the vagus nerve to improve the mood, suppressing the abnormal firing of brain neurons and stimulating the sites with the stellate ganglion distributed to modulate the hypothalamic function; ⑤ delivering the therapeutic regimens in association with the specific conditions and symptoms, and the classification of the physical signs on the base of the treatment of encephalopathy.

A Patient With Type 1 Diabetes and Acute Rhinosinusitis.

A 41-year-old with type 1 diabetes had generalized weakness, muffled voice, and slurred speech. Neck computed tomography showed soft-tissue gas in the nasopharynx and prevertebral fascia; examination of sinus mucosal samples identified numerous broad, nonseptate right-angled hyphae and fruiting bodies. What is the diagnosis and what would you do next?

Understanding immune microenvironment alterations in the brain to improve the diagnosis and treatment of diverse brain diseases.

Abnormal inflammatory states in the brain are associated with a variety of brain diseases. The dynamic changes in the number and function of immune cells in cerebrospinal fluid (CSF) are advantageous for the early prediction and diagnosis of immune diseases affecting the brain. The aggregated factors and cells in inflamed CSF may represent candidate targets for therapy. The physiological barriers in the brain, such as the blood‒brain barrier (BBB), establish a stable environment for the distribution of resident immune cells. However, the underlying mechanism by which peripheral immune cells migrate into the brain and their role in maintaining immune homeostasis in CSF are still unclear. To advance our understanding of the causal link between brain diseases and immune cell status, we investigated the characteristics of immune cell changes in CSF and the molecular mechanisms involved in common brain diseases. Furthermore, we summarized the diagnostic and treatment methods for brain diseases in which immune cells and related cytokines in CSF are used as targets. Further investigations of the new immune cell subtypes and their contributions to the development of brain diseases are needed to improve diagnostic specificity and therapy.

Current research status and reflection on acupuncture treatment for brain disorders. / é’ˆç¸æ²»ç–—è„‘ç— çš„ç ”ç©¶çŽ°çŠ¶ä¸Žæ€è€ƒ.

Acupuncture has demonstrated positive efficacy in the treatment of brain disorders. However, significant challenges lie in integrating acupuncture with modern technologies, promoting its clinical application in treating brain disorders, elucidating the mechanisms underlying acupuncture's preventive and therapeutic effects on brain disorders, and accelerating the pace of translational development in acupuncture medicine. This paper briefly outlines the current research status, challenges, and potential future directions in acupuncture treatment for brain disorders, aiming to provide essential insights for the modernization and development of acupuncture in the treatment of brain disorders.

Non-cirrhotic hyperammonaemic encephalopathy secondary to metastatic pancreatic neuroendocrine tumour treated with peptide receptor radio nucleotide therapy and transarterial chemoembolisation.

Neuroendocrine tumours (NETs) are rare cancers which often carry significant morbidity and mortality, frequently related to burden of liver metastases. Hyperammonaemia and subsequent hepatic encephalopathy carries a poor prognosis and has been described in these patients. We discuss a case of a woman in her 50s with hyperammonaemic encephalopathy and a new diagnosis of pancreatic NET with hepatic metastases. She presented with a reduced conscious state a few days post commencing chemotherapy. This was considered to have a multifactorial pathophysiology: the primary driver being large volume hepatic metastases and contributed by portosystemic microshunting, sepsis, severe weight loss and malnutrition. We describe how each of these exacerbating factors was addressed and highlight the effective multimodal treatment approach consisting of sequential transarterial chemoembolisation followed by peptide receptor radio nucleotide therapy, resulting in the resolution of hyperammonaemic encephalopathy and radiological partial metabolic response.

Establishing a regional registry for neonatal encephalopathy: impact on identification of gaps in practice.

BACKGROUND: Neonatal encephalopathy (NE) continues to be a significant risk for death and disability. To address this risk, regional guidelines were developed with the support of a malpractice insurance patient safety organization. A NE registry was also established to include 14 centers representing around 50% of deliveries in the state of Massachusetts. The aim of this study was to identify areas of variation in practice that could benefit from quality improvement projects. METHODS: This manuscript reports on the establishment of the registry and the primary findings to date. RESULTS: From 2018 to 2020, 502 newborns with NE were evaluated for Therapeutic Hypothermia (TH), of which 246 (49%) received TH, representing a mean of 2.91 per 1000 live births. The study reports on prenatal characteristics, delivery room resuscitation, TH eligibility screening, and post-natal management of newborns with NE who did and did not receive TH. CONCLUSIONS: The registry has allowed for the identification of areas of variation in clinical practices, which have guided ongoing quality improvement projects. The authors advocate for the establishment of local and regional registries to standardize and improve NE patient care. They have made the registry data collection tools freely available for other centers to replicate this work. IMPACT: Malpractice insurance companies can take an active role in supporting clinicians in establishing clinical practice guidelines and regional registries. Establishing a collaborative regional neonatal encephalopathy (NE) registry is feasible. Data Collection tools for a NE registry have been made publicly available to be adopted and replicated by other groups. Establishing a regional NE registry allowed for the identification of gaps in knowledge, variations in practice, and the opportunity to advance care through quality improvement projects.

Therapeutic plasma exchange in refractory Susac's syndrome: A brief report.

Susac's syndrome (SuS) is an autoimmune endotheliopathy that typically presents with the clinical triad of encephalopathy, hearing loss, and branch retinal artery occlusion. It has a wide range of possible presentations, and its pathogenesis remains uncertain. Fulminant and refractory cases are difficult to treat, and no standard treatment protocol has been established. However, therapeutic plasma exchange (TPE) has been described as an adjunctive therapy in several SuS cases. Herein we present a case of a 63-year-old male with debilitating encephalopathy and recent hearing and vision loss, who responded favorably to TPE. Given this and other published reports of plasma exchange therapy for SuS, treatment protocols should consider TPE in early stages of disease.

Application of in vivo brain imaging technology in the basic research of acupuncture-moxibustion for encephalopathy. / æ´»ä½“è„‘æˆåƒæŠ€æœ¯åœ¨é’ˆç¸è„‘ç— åŸºç¡€ç ”ç©¶ä¸­çš„åº”ç”¨.

Acupuncture-moxibustion is remarkably effective on encephalopathy, but its mechanism is unclear. With the continuous development of imaging technology, the in vivo brain imaging technology has been used increasingly in life science research and it also becomes a more effective tool for the basic research of acupuncture-moxibustion in treatment of encephalopathy. The paper summarizes the application of its technology in the basic research of acupuncture-moxibustion for encephalopathy and the characteristics of imaging, as well as the advantages and shortcomings. It is anticipated that the references may be provided for the basic research of acupuncture-moxibustion in treatment of encephalopathy and be conductive to the modernization of acupuncture-moxibustion.

Troponin-T value as a prognostic marker in neonates diagnosed with neonatal encephalopathy and receiving hypothermia treatment.

OBJECTIVE: The aim of this study was to investigate the effect of Troponin-T levels on the prognosis of neonatal encephalopathy (NE). PATIENTS AND METHODS: The study included one hundred and eleven newborns diagnosed with NE and receiving hypothermia treatment. The cases were separated into 2 groups according to the SARNAT classification as Stage 2 or Stage 3. The groups were compared in respect of anthropometric characteristics, APGAR scores, and biochemical parameters. The cases were also separated into 3 groups according to the Troponin-T levels and were compared with respect to the clinical course. RESULTS: The serum Troponin-T (p=0.012), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (p<0.0001), and lactate levels (p=0.04) in the Sarnat Stage 3 group were statistically significantly higher than in the Sarnat stage 2 group. A significant positive correlation was determined between the Troponin-T level and the total duration of respiratory support (r=0.20, p=0.03). A significant positive correlation was determined between the ALT/AST ratio and the length of stay in hospital (r=0.29, p=0.001), duration of intubation (r=0.32, p=0.01), and total duration of respiratory support (r=0.36, p<0.001). A statistically significant difference was determined in mortality rates between the 3 subgroups of Troponin-T levels; Group 1: 2.8%, Group 2:5.4%, and Group 3: 15.8%. (p=0.04, χ²=4.74). A cut-off value of 164 ng/L for Troponin-T was determined to predict mortality with 77% sensitivity and 67% specificity (AUC=0.73, p=0.023). When the groups were compared according to Troponin-T level, a statistically significant difference was determined in respect of length of stay in hospital (p=0.03, χ²=6.95) and total duration of oxygen support (p=0.01, χ²=9.12). CONCLUSIONS: The serum Troponin-T level can be evaluated as a prognostic marker in cases followed up with a diagnosis of NE and receiving hypothermia treatment. There is a need for further prospective studies with larger samples on this subject.

Circular RNAs: Diagnostic and Therapeutic Perspectives in CNS Diseases.

Circular RNAs (circRNAs) are a class of regulatory non-coding RNAs characterized by the presence of covalently closed ends. A growing body of evidence suggests that circRNAs play important roles in physiology and pathology. In particular, accumulating data on circRNA functions in various central nervous system (CNS) diseases and their correlations indicate that circRNAs are critical contributors to the onset and development of brain disorders. In this review, we focus on the regulatory and functional roles of circRNAs in CNS diseases, highlighting their diagnostic and therapeutic potential, with the aim of providing new insights into CNS diseases.