Expert Review of Neurotherapeutics最新文献

Introduction: Disorders of consciousness (DoC) are characterized by impaired arousal and/or awareness, ranging from coma to unresponsive wakefulness syndrome, minimally conscious state, and cognitive motor dissociation. Pharmacological treatment options remain limited, complicated by the heterogeneity of etiologies, such as traumatic brain injury, stroke, and infections. The lack of rigorous clinical trials has led to off-label use of treatments, often without clear mechanistic understanding, posing challenges for effective patient care.

Areas covered: In this perspective, the authors report on key studies concerning the effectiveness of pharmacological interventions, including dopaminergic and GABAergic agents, antidepressants, statins, and anticonvulsants, in promoting recovery of consciousness in DoC.

Expert opinion: Robust longitudinal clinical trials are needed, with priority given to early subacute phase intervention. Outcomes should be better defined, considering immediate responses to medication while also increasing the emphasis on long-term quality of life. Unified functional and mechanistic frameworks are needed to guide research and foster collaboration. Furthermore, a shift toward personalized medicine would benefit this heterogeneous population. Moving forward, assessing the efficacy of more unconventional or 'paradoxical' pharmacological options in treatment plans will be essential. The authors also expect an increased use of AI tools to identify factors that best predict treatment responses.

Introduction: Acute ischemic stroke (AIS) is the second leading cause of death and one of the leading causes of long-term disability globally. Endovascular thrombectomy (EVT) has revolutionized treatment for large vessel occlusion (LVO), providing 20% increase in post-stroke functional independence compared to intravenous thrombolysis (IVT) alone. Despite its proven efficacy, EVT is underutilized. While it is suitable for at least 15-20% of AIS patients, its mean adoption ranges from less than 1% to 7% in different areas.

Areas covered: This review highlights key findings from pivotal randomized controlled trials and real-world data, focusing on patient selection criteria, advancements in thrombectomy devices, and procedural innovations. A comprehensive literature search was performed using PubMed, Scopus, EMBASE and the Cochrane Library for relevant randomized controlled trials and observational studies.

Expert opinion: Disparity in access to EVT requires strategic investments in healthcare systems and international multidisciplinary collaboration. Enhancing geographic coverage with thrombectomy-capable centers and optimizing prehospital triage systems are essential. Bridging the gap between treatment capability and real-world implementation is critical to improving global AIS outcomes.

Background: Current models primarily predict outcomes before thrombolytic therapy. This study explored if systemic bleeding during thrombolysis predicts hemorrhagic transformation (HT) within 36 hours post-thrombolysis.

Research design and methods: Data from 591 acute ischemic stroke patients treated with rt-PA at Wenzhou Central Hospital (2016-2023) were prospectively collected and analyzed. The incidence of systemic bleeding was compared with the Stroke Prognostication using Age and the National Institutes of Health Stroke Scale (Span100) index, as well as the Hemorrhage After Thrombolysis (HAT) scale.

Results: Systemic bleeding occurred in 285 patients, including 92 with HT. The HT rate was significantly higher in patients with late-onset oral bleeding (35.90%) or other systemic bleeding (38.89%) than in those without (p < 0.01). Late-onset oral and systemic bleeding during thrombolysis predicted HT in anterior circulation infarction (p < 0.001) but not in posterior circulation infarction (p = 0.70). The AUC for predicting HT was 0.578 for these bleeding types, versus 0.568 for Span-100 and 0.61 for HAT. Incorporating bleeding types increased Span-100 sensitivity to 0.623 and HAT to 0.648.

Conclusions: Late-onset oral and other systemic bleeding during thrombolysis effectively predict HT in anterior circulation infarction, enhancing the sensitivity of Span100 and HAT scales when combined.

Introduction: Schizotypal personality disorder (SPD) has a long history, and there is still considerable ongoing research. Although there are overlapping features of SPD and other personality disorders, the full constellation of schizotypal features is broader. The longitudinal course of SPD is variable, with differences in trajectory manifesting lifelong clinical significance. Particularly important is the relationship between SPD and prodromal states that may result in an eventual diagnosis of psychosis.

Areas covered: This review covers the history and differential diagnosis of SPD, including the older conceptualization of 'borderline schizophrenia.' Clinical, cognitive, functional, brain imaging, and genetic features of SPD, and the implications of age at onset and method of ascertainment of the condition are reviewed. Differences between psychometrically identified schizotypy, clinically diagnosed SPD, and other psychiatric conditions are described. A comprehensive literature search using MEDLINE (via PubMed) did not specify a date range, to capture the full scope of research.

Expert opinion: SPD is unique in that the age at ascertainment is critical for the persistence of the diagnosis. When diagnosed with SPD in late adolescence, some individuals develop psychosis, some remit, and others have persistent, lifelong symptoms. Predictors of conversion to psychosis have been identified but are no proven treatments.

Introduction: Glioblastoma (GBM), a highly malignant brain tumor, has a poor prognosis despite standard treatments like surgery, chemotherapy, and radiation. Glioblastoma stem cells (GSCs) play a critical role in recurrence and therapy resistance. Stem cell-based therapies have emerged as innovative approaches, leveraging the tumor-targeting abilities of stem cells to deliver treatments directly to GBM.

Areas covered: This review focuses on using intact stem cells or subtypes for GBM therapy, excluding antigenic characteristics. The stem cell-based therapies explored include neural, mesenchymal, glioblastoma, hematopoietic and adipose-derived stem cells that have been investigated in both clinical and preclinical settings. A systematic search in PubMed, EMBASE, ClinicalTrials.gov, and Scopus had identified research up until January 2024. Key mechanisms reviewed include immune modulation, angiogenesis inhibition, and apoptosis induction. Discussion of completed and ongoing trials include emphasis on safety, efficacy, challenges, and study design limitations.

Expert opinion: Stem cell-based therapies hold promise for treating GBM by targeting GSCs and improving treatment outcomes. Despite some potential advantages, challenges such as tumorigenesis risks, delivery complexities, and sustained therapeutic effects persist. Future research should prioritize optimizing stem cell modifications, combining them with current treatments, and conducting large-scale trials to ensure safety and efficacy. Integrating stem cell therapies into GBM treatment could provide more effective and less invasive options for patients.

Background: Cannabis-based medicinal products (CBMPs) are a potential treatment for post-traumatic stress disorder (PTSD), but their long-term efficacy and safety need further investigation. This study assessed the changes in health-related quality of life (HRQoL) and adverse events in PTSD patients prescribed CBMPs.

Research design and methods: This observational cohort study included PTSD patients enrolled on the UK Medical Cannabis Registry for 18 months or longer. Changes in PTSD-specific symptoms (IES-R), anxiety (GAD-7), sleep quality (SQS), and general HRQoL (EQ-5D-5 L) were assessed at 1, 3, 6, 12, and 18 months.

Results: In 269 patients, significant improvements in PTSD symptoms, anxiety, sleep quality, and HRQoL were observed at all follow-up points (p < 0.001). On multivariate logistic regression, male gender (OR = 0.51; 95% CI:0.28-0.94; p = 0.034) was associated with a reduced chance of reporting improvements in IES-R. Adverse events were reported by 70 (26.02%) patients, with insomnia (n = 42, 15.61%) and fatigue (n = 40, 14.87%) being the most common.

Conclusions: CBMPs were associated with improvements in PTSD symptoms, anxiety, sleep, and HRQoL at up to 18 months. Although the study's observational nature limits causal conclusions, these findings support further assessment of medical cannabis.

Trial registration: This is an observational study and is not registered as a clinical trial.

Introduction: As the world population ages, Alzheimer disease (AD) prevalence increases. However, understanding of AD etiology continues to evolve, and the pathophysiological processes involved are only partially elucidated. One compound suspected to play a role in the development and progression of AD is cholesterol. Several lines of evidence support this connection, yet it remains unclear whether cholesterol-modifying strategies have potential applications in the clinical management of AD.

Areas covered: A deep literature search using PubMed was performed to prepare this narrative review. The literature search, performed in early 2024, was inclusive of literature from 1990 to 2024. After providing an overview of cholesterol metabolism, this study summarizes key preclinical studies that have investigated cholesterol-modifying therapies in laboratory models of AD. It also summarizes past and current clinical trials testing specific targets modulated by anti-cholesterol therapies in AD patients.

Expert opinion: Based on current epidemiological and mechanistic studies, cholesterol likely plays a role in AD etiology. The use of cholesterol-modifying therapies could be a promising treatment approach if administered at presymptomatic to early AD phases, but it is unlikely to be efficient in mild, moderate, and late AD stages. Several recommendations are provided for hypercholesterolemia management in AD patients.

Introduction: Cenobamate (CNB) is an anti-seizure medication (ASM) utilized for drug-resistant focal-onset seizures, which are difficult to manage with usual agents. Previous studies demonstrated that it can be effective in patients with refractory epilepsy.

Methods: The MEDLINE, Cochrane, and Scopus databases were systematically searched up to 24 October 2024. A Random-effects model was employed to compute the Mean Difference (MD) and the Risk Ratio (RR) with 95% Confidence Intervals (CI). Statistical Analyses were performed utilizing RStudio 4.4.2.

Results: Four studies were included, comprising 906 patients; 527 (59%) received CNB as add-on therapy. The results indicated that the 50% responder rate (RR 1.77; 95% CI: 1.28 to 2.44, p = 0.000551, I² = 70.3%) and seizure freedom (RR of 3.09; 95% CI: 1.91 to 5.00, p = 0.000004, I² = 8.7%) were significantly higher in this group.

Conclusions: In this meta-analysis of four studies, CNB as an add-on therapy significantly reduced seizure frequency in patients with uncontrolled focal seizures, making it a promising option for improved seizure control and quality of life.

Introduction: Schizophrenia is among the most debilitating mental health conditions. While antipsychotic medication represents the primary pillar of treatment, guidelines now also recommend psychotherapy. Metacognitive Training (MCT) has emerged over the past 20 years as a novel approach that addresses the cognitive biases involved in the pathogenesis of schizophrenia. MCT seeks to enhance patients' awareness of their cognitive distortions and reduce overconfidence. MCT is available in individual and group formats.

Areas covered: This review provides a comprehensive overview of MCT, detailing its theoretical foundations, development, and implementation. The authors present meta-analyses demonstrating its efficacy in improving positive symptoms as well as negative symptoms and self-esteem. Lastly, the review covers the integration of the COGITO app to support MCT. For our narrative review we searched data bases including PubMed, Web of Science, EMBASE, PsycINFO, and MEDLINE.

Expert opinion: MCT represents a significant advance in the treatment of schizophrenia, offering a flexible, low-threshold intervention that can be easily implemented in various clinical settings. The training's focus on metacognitive processes provides patients with tools to understand and manage their symptoms. Future research should seek to develop shortened as well as more personalized versions and investigate the long-term sustainability of the effects.