Therapeutic role of PTEN in tissue regeneration for management of neurological disorders: stem cell behaviors to an in-depth review.

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) represents the initial tumor suppressor gene identified to possess phosphatase activity, governing various cellular processes including cell cycle regulation, migration, metabolic pathways, autophagy, oxidative stress response, and cellular senescence. Current evidence suggests that PTEN is critical for stem cell maintenance, self-renewal, migration, lineage commitment, and differentiation. Based on the latest available evidence, we provide a comprehensive overview of the mechanisms by which PTEN regulates activities of different stem cell populations and influences neurological disorders, encompassing autism, stroke, spinal cord injury, traumatic brain injury, Alzheimer's disease and Parkinson's disease. This review aims to elucidate the therapeutic impacts and mechanisms of PTEN in relation to neurogenesis or the stem cell niche across a range of neurological disorders, offering a foundation for innovative therapeutic approaches aimed at tissue repair and regeneration in neurological disorders. This review unravels novel therapeutic strategies for tissue restoration and regeneration in neurological disorders based on the regulatory mechanisms of PTEN on neurogenesis and the stem cell niche.

Making a difference: neurological support in the community.

Nearly 3 million people in the UK have a neurological condition; stroke, traumatic brain injury, Parkinson's disease, multiple sclerosis, brain tumour, motor neurone disease, among others - all affecting the person for the rest of their life. The NHS provides treatment at the onset of a condition but after that, there is a huge need for ongoing support. Research shows that those who are supported and know more about their condition are less likely to have to call on further in-hospital and GP care. There is enormous scope for improving the quality of life for those with neurological conditions. The right support-therapeutic and social-makes all the difference. The book, which this article is based on, shows how those with neurological conditions benefit from integrated ongoing support provided in the local community and self-help, and how lives can be improved. It explains good practice and encouraging methods in the support and treatment of those with life changing conditions.

Painful Eyes in Neurology Clinic: A Guide for Neurologists.

Eye pain is a common complaint among patients presenting to the neurology clinic. It can be related to neurologic diseases, but it can also be a localized eye condition. Such disorders can be misleading, as their benign appearance might mask more grave underlying conditions, potentially leading to misdiagnoses or delayed treatment. Clinicians should be aware of the specific neurologic or systemic disorders (eg, demyelinating diseases or vascular abnormalities) that might first manifest as eye pain. Formal ophthalmic consultation is recommended for patients presenting with eye pain as the predominant complaint especially when red flags for more serious pathology are present.

Meaning-Making Among Parents of Children With Severe Neurologic Impairment in the PICU.

BACKGROUND AND OBJECTIVES: Parents and family caregivers of children with severe neurologic impairment (SNI) experience many stressors, especially during their child's critical illness. This study aimed to examine parent experiences around the time of their child's PICU care to explore ways parents make meaning in relation to these stressors. METHODS: This qualitative study of data from a single center in the United States followed Consolidated Criteria for Reporting Qualitative Research guidelines. One to one semistructured interviews queried parents' psychosocial well-being around the time of their child's PICU care. Eligible participants had a child with an SNI condition for >3 months admitted to the PICU for >24 hours with an expected length of stay >1 week. RESULTS: Data were analyzed by a research team with expertise in palliative care, psychology, critical care, and qualitative methods. Fifteen family caregivers of 15 children participated. Children were a median of 8 years old (interquartile range 4-11.5) and 80% (n = 12) had congenital/genetic conditions. Parent/family caregivers were a median age of 39 years old (interquartile range 36-42.5); 20% (n = 3) self-identified as fathers and 47% (n = 7) as having to a minority racial background. Parents discussed ongoing meaning-making that occurred through domains of comprehension and purpose, and themes of understanding of other people and the world around them. Subthemes focused on appreciation/acceptance, adaptability/accountability, valuing all lives, and learning/teaching about their child. CONCLUSIONS: Meaning-making may be an opportunity for support in the PICU among parents/family caregivers of children with SNI.

Long-term treatment outcomes and natural course of low-grade intracranial dural arteriovenous fistulas.

OBJECTIVE: In contrast to high-grade dural arteriovenous fistula (dAVF), low-grade dAVF is mainly associated with tinnitus and carries a low risk of morbidity and mortality. It remains unclear whether the benefits of active interventions outweigh the associated risk of complications in low-grade dAVF. METHODS: The authors conducted a retrospective single-center study that included all consecutive patients diagnosed with an intracranial low-grade dAVF (Cognard type I and IIa) during 2012-2022 with DSA. The authors analyzed symptom relief, symptomatic angiographic cure, treatment-related complications, risk for intracerebral hemorrhage (ICH), and mortality. All patients were followed up until the end of 2022. RESULTS: A total of 81 patients were diagnosed with a low-grade dAVF. Of these, 48 patients (59%) underwent treatment (all primary endovascular treatments), and 33 patients (41%) did not undergo treatment. Nine patients (19%) underwent retreatments. Angiographic follow-up was performed after median (IQR) 7.7 (6.1-24.1) months by means of DSA (mean 15.0, median 6.4 months, range 4.5-83.4 months) or MRA (mean 29.3, median 24.7 months, range 5.9-62.1 months). Symptom control was achieved in 98% of treated patients after final treatment. On final angiographic follow-up, 73% of patients had a completely occluded dAVF. There were 2 treatment-related complications resulting in 1 transient (2%) and 1 permanent (2%) neurological complication. One patient showed recurrence and progression of a completely occluded low-grade dAVF to an asymptomatic high-grade dAVF. No cases of ICH- or dAVF-related mortality were found in either treated patients (median [IQR] follow-up 5.1 [2.0-6.8] years) or untreated patients (median [IQR] follow-up 5.7 [3.2-9.0] years). CONCLUSIONS: Treatment of low-grade dAVF provides a high rate of symptom relief with small risks for complications with neurological sequela. The risks of ICH and mortality in patients with untreated low-grade dAVF are minimal. Symptoms may not reveal high-grade recurrence, and radiological follow-up may be warranted in selected patients with treated low-grade dAVF. An optimal radiographic follow-up regimen should be developed by a future prospective multicenter registry.

Symptom Management in Children Who Are Neurologically Impaired for the Primary Care Medical Home.

Children with neurologic impairment are a growing population of pediatric patients who require care from a large team of physicians to maintain their health. These children often have similar clinical patterns and symptoms that occur because of their neurologic impairment. Families often seek care first from their primary care home to identify and guide initial steps in management. Identifying the symptoms outlined in the 4 cases in this article will help alleviate consequences of delayed care for these patients and provide opportunities for shared decision-making with the family's goals of care for their child. [Pediatr Ann. 2024;53(3):e82-e87.].

Exploring the Therapeutic Potential of Peritoneal Dialysis (PD) in the Treatment of Neurological Disorders.

Peritoneal dialysis (PD) is a well-established renal replacement therapy commonly employed in clinical practice. While its primary application is in the treatment of kidney disease, its potential in addressing other systemic disorders, including neurological diseases, has garnered increasing interest. This study provides a comprehensive overview of the related technologies, unique advantages, and clinical applications of PD in the context of neurological disorders. By exploring the mechanism underlying PD, its application in neurological diseases, and associated complications, we addressed the feasibility and benefits of PD as an adjunct therapy for various neurological conditions. Our study aims to highlight its role in detoxification and symptom management, as well as its advantages over other universally accepted methods of renal replacement therapy. Our goal is to bring to the spotlight the therapeutic potential of PD in neurological diseases, such as stroke, stimulate further research, and broaden the scope of its application in the clinical setting.

[Hematologic Diseases and Neurological Complications].

Many hematologic diseases can be complicated by neurological symptoms during the disease course. Hematologic diseases can contribute to strokes and neuropathies; thus, neurologists should be aware of them. Recent reports have increased of neurological side effects associated with new anticancer therapies such as immune checkpoint inhibitors and chimeric antigen receptor-T cell therapy. The relationship between hematologic diseases and neurological complications is expected to become more prevalent.

Nursing assessment and care for a patient with a neurological disorder.

The previous article discussed the pathophysiology involved in disorders of the nervous system. Having considered some of the most prevalent disorders, this second part uses a case study to explore effective patient assessment and emphasise the importance of facilitating patient self-management for improved outcomes. By addressing these key aspects, nursing professionals can enhance the quality of care and the support provided to individuals experiencing neurological disorders.

Protective effects of fecal microbiota transplantation against ischemic stroke and other neurological disorders: an update.

The bidirectional communication between the gut and brain or gut-brain axis is regulated by several gut microbes and microbial derived metabolites, such as short-chain fatty acids, trimethylamine N-oxide, and lipopolysaccharides. The Gut microbiota (GM) produce neuroactives, specifically neurotransmitters that modulates local and central neuronal brain functions. An imbalance between intestinal commensals and pathobionts leads to a disruption in the gut microbiota or dysbiosis, which affects intestinal barrier integrity and gut-immune and neuroimmune systems. Currently, fecal microbiota transplantation (FMT) is recommended for the treatment of recurrent Clostridioides difficile infection. FMT elicits its action by ameliorating inflammatory responses through the restoration of microbial composition and functionality. Thus, FMT may be a potential therapeutic option in suppressing neuroinflammation in post-stroke conditions and other neurological disorders involving the neuroimmune axis. Specifically, FMT protects against ischemic injury by decreasing IL-17, IFN-γ, Bax, and increasing Bcl-2 expression. Interestingly, FMT improves cognitive function by lowering amyloid-ß accumulation and upregulating synaptic marker (PSD-95, synapsin-1) expression in Alzheimer's disease. In Parkinson's disease, FMT was shown to inhibit the expression of TLR4 and NF-κB. In this review article, we have summarized the potential sources and methods of administration of FMT and its impact on neuroimmune and cognitive functions. We also provide a comprehensive update on the beneficial effects of FMT in various neurological disorders by undertaking a detailed interrogation of the preclinical and clinical published literature.

Recommendations for optimal interdisciplinary management and healthcare settings for patients with rare neurological diseases.

BACKGROUND: In 2017, the German Academy for Rare Neurological Diseases (Deutsche Akademie für Seltene Neurologische Erkrankungen; DASNE) was founded to pave the way for an optimized personalized management of patients with rare neurological diseases (RND) in all age groups. Since then a dynamic national network for rare neurological disorders has been established comprising renowned experts in neurology, pediatric neurology, (neuro-) genetics and neuroradiology. DASNE has successfully implemented case presentations and multidisciplinary discussions both at yearly symposia and monthly virtual case conferences, as well as further educational activities covering a broad spectrum of interdisciplinary expertise associated with RND. Here, we present recommendation statements for optimized personalized management of patients with RND, which have been developed and reviewed in a structured Delphi process by a group of experts. METHODS: An interdisciplinary group of 37 RND experts comprising DASNE experts, patient representatives, as well as healthcare professionals and managers was involved in the Delphi process. First, an online collection was performed of topics considered relevant for optimal patient care by the expert group. Second, a two-step Delphi process was carried out to rank the importance of the selected topics. Small interdisciplinary working groups then drafted recommendations. In two consensus meetings and one online review round these recommendations were finally consented. RESULTS: 38 statements were consented and grouped into 11 topics: health care structure, core neurological expertise and core mission, interdisciplinary team composition, diagnostics, continuous care and therapy development, case conferences, exchange / cooperation between Centers for Rare Diseases and other healthcare partners, patient advocacy group, databases, translation and health policy. CONCLUSIONS: This German interdisciplinary Delphi expert panel developed consented recommendations for optimal care of patients with RND in a structured Delphi process. These represent a basis for further developments and adjustments in the health care system to improve care for patients with RND and their families.

CRISPR-Based Gene Editing Techniques in Pediatric Neurological Disorders.

The emergence of gene editing technologies offers a unique opportunity to develop mutation-specific treatments for pediatric neurological disorders. Gene editing systems can potentially alter disease trajectory by correcting dysfunctional mutations or therapeutically altering gene expression. Clustered regularly interspaced short palindromic repeats (CRISPR)-based approaches are attractive gene therapy platforms to personalize treatments because of their specificity, ease of design, versatility, and cost. However, many such approaches remain in the early stages of development, with ongoing efforts to optimize editing efficiency, minimize unintended off-target effects, and mitigate pathologic immune responses. Given the rapid evolution of CRISPR-based therapies, it is prudent for the clinically based child neurologist to have a conceptual understanding of what such therapies may entail, including both benefits and risks and how such therapies may be clinically applied. In this review, we describe the fundamentals of CRISPR-based therapies, discuss the opportunities and challenges that have arisen, and highlight preclinical work in several pediatric neurological diseases.

RNA therapeutics for neurological disease.

Neurological disorders are the group of diseases that primarily affect the center nervous system, which could lead to a significant negative impact on the ability of learning new skills, speaking, breathing, walking, judging, making decision, and other essential living skills. In the last decade, neurological disorders have significantly increased their impact to our community and become the one of leading causes of disability and death. The World Health Organization has identified neurological disorders including Alzheimer's disease and other dementia as the health crisis for the modern life. Tremendous ongoing research efforts focus on understanding of disease genetics, molecular mechanisms and developing therapeutic interventions. Because of the urgent need of the effective therapeutics and the recent advances in the toolkits and understanding for developing more drug-like RNA molecules, there is a growing interest for developing RNA therapeutics for neurological disorders. This article will discuss genetics and mechanisms of neurological disorders and how RNA-based molecules have been used to develop therapeutics for this group of diseases, challenges of RNA therapeutics and future perspectives on this rising therapeutic intervention tool.

Brain-computer interface digital prescription for neurological disorders.

Neurological and psychiatric diseases can lead to motor, language, emotional disorder, and cognitive, hearing or visual impairment By decoding the intention of the brain in real time, the Brain-computer interface (BCI) can first assist in the diagnosis of diseases, and can also compensate for its damaged function by directly interacting with the environment; In addition, provide output signals in various forms, such as actual motion, tactile or visual feedback, to assist in rehabilitation training; Further intervention in brain disorders is achieved by close-looped neural modulation. In this article, we envision the future BCI digital prescription system for patients with different functional disorders and discuss the key contents in the prescription the brain signals, coding and decoding protocols and interaction paradigms, and assistive technology. Then, we discuss the details that need to be specially included in the digital prescription for different intervention technologies. The third part summarizes previous examples of intervention, focusing on how to select appropriate interaction paradigms for patients with different functional impairments. For the last part, we discussed the indicators and influencing factors in evaluating the therapeutic effect of BCI as intervention.

Exosomes: potential targets for the diagnosis and treatment of neuropsychiatric disorders.

The field of neuropsychiatry is considered a middle ground between neurological and psychiatric disorders, thereby bridging the conventional boundaries between matter and mind, consciousness, and function. Neuropsychiatry aims to evaluate and treat cognitive, behavioral, and emotional disorders in individuals with neurological conditions. However, the pathophysiology of these disorders is not yet fully understood, and objective biological indicators for these conditions are currently lacking. Treatment options are also limited due to the blood-brain barrier, which results in poor treatment effects. Additionally, many drugs, particularly antipsychotic drugs, have adverse reactions, which make them difficult to tolerate for patients. As a result, patients often abandon treatment owing to these adverse reactions. Since the discovery of exosomes in 1983, they have been extensively studied in various diseases owing to their potential as nanocellulators for information exchange between cells. Because exosomes can freely travel between the center and periphery, brain-derived exosomes can reflect the state of the brain, which has considerable advantages in diagnosis and treatment. In addition, administration of engineered exosomes can improve therapeutic efficacy, allow lesion targeting, ensure drug stability, and prevent systemic adverse effects. Therefore, this article reviews the source and biological function of exosomes, relationship between exosomes and the blood-brain barrier, relationship between exosomes and the pathological mechanism of neuropsychiatric disorders, exosomes in the diagnosis and treatment of neuropsychiatric disorders, and application of engineered exosomes in neuropsychiatric disorders.

Engineered exosomes derived from stem cells: a new brain-targeted strategy.

INTRODUCTION: Using engineered exosomes produced from stem cells is an experimental therapeutic approach for treating brain diseases. According to reports, preclinical research has demonstrated notable neurogenesis and angiogenesis effects using modified stem cell-derived exosomes. These biological nanoparticles have a variety of anti-apoptotic, anti-inflammatory, and antioxidant properties that make them very promising for treating nervous system disorders. AREAS COVERED: This review examines different ways to enhance the delivery of modified stem cell-derived exosomes, how they infiltrate the blood-brain barrier (BBB), and how they facilitate their access to the brain. We would also like to determine whether these nanoparticles have the most significant transmission rates through BBB when targeting brain lesions. EXPERT OPINION: Using engineered stem cell-derived exosomes for treating brain disorders has generated considerable attention toward clinical research and application. However, stem cell-derived exosomes lack consistency, and their mechanisms of action are uncertain. Therefore, upcoming research needs to prioritize examining the underlying mechanisms and strategies via which these nanoparticles combat neurological disorders.

Imaging of brain barrier inflammation and brain fluid drainage in human neurological diseases.

The intricate relationship between the central nervous system (CNS) and the immune system plays a crucial role in the pathogenesis of various neurological diseases. Understanding the interactions among the immunopathological processes at the brain borders is essential for advancing our knowledge of disease mechanisms and developing novel diagnostic and therapeutic approaches. In this review, we explore the emerging role of neuroimaging in providing valuable insights into brain barrier inflammation and brain fluid drainage in human neurological diseases. Neuroimaging techniques have enabled us not only to visualize and assess brain structures, but also to study the dynamics of the CNS in health and disease in vivo. By analyzing imaging findings, we can gain a deeper understanding of the immunopathology observed at the brain-immune interface barriers, which serve as critical gatekeepers that regulate immune cell trafficking, cytokine release, and clearance of waste products from the brain. This review explores the integration of neuroimaging data with immunopathological findings, providing valuable insights into brain barrier integrity and immune responses in neurological diseases. Such integration may lead to the development of novel diagnostic markers and targeted therapeutic approaches that can benefit patients with neurological disorders.