Current Neurology and Neuroscience Reports最新文献

Purpose of review: The purpose of this article is to provide an update on cancer-related neuropathies over the past five years, by reviewing the advances in pathophysiology and biology, diagnostic approaches, and management strategies.

Recent findings: New agents causing peripheral neuropathy include antibody-drug conjugates, combinations of immune-checkpoint inhibitor therapies, and targeted therapies. Development of axonal neuropathies has been found to be mediated through the protein sterile-α and Toll/interleukin 1 receptor motif containing protein 1 (SARM1). There have been emerging imaging modalities such as high-field MRI and neuromuscular ultrasound, and serum biomarkers, such as neurofilament light chain and glial fibrillary acid protein. Though calmangafodipir was negative for preventing peripheral neuropathy in oxaliplatin-based treatments, the POLAR trial randomizing patients to cooling or compression of the dominant hand during taxane administration significantly reduced incidence of chemotherapy-induced peripheral neuropathy. As of yet, there are no treatments for chemotherapy-induced peripheral neuropathy, but continued basic research into the SARM pathway is likely to yield novel agents that will stop, or prevent, the process.

Purpose of review: Virotherapy has emerged as a promising approach to cancer treatment. Over the past two decades, early-phase clinical trials have demonstrated the safety and promising efficacy of virotherapy in subsets of cancer patients. However, a significant knowledge gap needs to be filled to propel the field further and achieve substantial anti-cancer benefits for more than the current 10-20% of treated patients. This article reviews the most relevant current challenges in cancer virotherapy.

Recent findings: Recent clinical observations suggest that patients who respond to virotherapy experience a shift in their immune response from an initial or concomitant response against the virus toward the tumor. Strategies aimed at facilitating the temporary escape of the virus from the immune response and ultimately redirecting the immune response from the virus to the tumor may propel the development of cancer viroimmunotherapy as a potent and versatile approach to cancer treatment. Here, we examine this issue and other current challenges in cancer virotherapy.

Purpose of review: Wilson disease (WD), an uncommon autosomal recessive (AR) hereditary disorder characterized by abnormal accumulation of copper primarily in the liver and secondarily in other organs like the brain, is caused by a deficiency in the ATP7B transporter gene. The key to successful therapy is early diagnosis.

Recent findings: Mutant genes need to be inherited from both parents for phenotypic expression. The ATP7B gene located on chromosome 13q14.3 comprises 20 introns and 21 exons, encodes a protein of 165 amino acids, and this helps in incorporation of copper into ceruloplasmin, the copper binding protein. So far, more than 800 mutations have been reported, of which 380 have confirmed involvement in the pathogenesis of WD. The most common mutations are H1069Q and R778L in European and Asian populations respectively. Approximately 90%-98% of WD subjects are heterozygous, showing different mutations in each of the alleles encoding the ATP7B. Conversely, the phenotype and the penetrance of WD can be extremely variable. Even patients carrying two disease-causing mutations do not necessarily have a demonstrable alteration of copper metabolism. Considering the possibility of late-onset disease, asymptomatic cases, and phenotypic variability, it is crucial to evaluate previous and future generations of the index case. WD ranges from being asymptomatic in some patients to result in acute liver failure and/or a variety of neuropsychiatric disorders among others. Although WD may be present at any age, is more common between the ages of 5 and 35 years. However, it should be investigated in patients with liver failure of unknown cause and those with liver disease associated with neuropsychiatric symptomatology. Diagnosis requires a combination of clinical signs and symptoms, as well as relevant diagnostic tests such as measurement of serum ceruloplasmin, urinary excretion of copper, liver biopsy or genetic testing. Treatment is lifelong and includes chelating agents (penicillamine and trientine) and inhibitors of copper absorption (zinc salts). Liver transplant is an option for patients with end-stage liver disease. The key to successful therapy is early diagnosis.

Purpose of review: This article explores the intricate relationship between androgens, androgen receptors, and the central nervous system. We examine the role of physiologically derived androgens and androgenic supplements in neurodevelopment and neuroplasticity and delve into the involvement of androgen pathways in the pathogenesis of various neurological disorders.

Recent findings: This review highlights the increasing recognition of testosterone and androgen signaling in various neurological conditions, with evidence of both protective and harmful effects depending on dosage and context. Although limited to experimental use, testosterone replacement therapy (TRT) may serve potential benefits in the management of multiple sclerosis, epilepsy, headache, Duchenne muscular dystrophy, amyotrophic lateral sclerosis, and Parkinson disease. On the other hand, androgen-blocking treatments may help alter disease progression in spinal and bulbar muscular atrophy. Testosterone supplementation can have potential adverse events when used at a supratherapeutic level, and prenatal testosterone exposure is believed to contribute to the pathogenesis of neurodevelopmental disease. Additionally, androgen-blocking agents could increase the risk of neurodegenerative conditions, such as Parkinson disease and Alzheimer disease. Despite the above findings, there is no established indication of TRT or androgen-blocking medication in neurological disorders. The body of evidence highlighting the involvement of androgens and androgen receptors (ARs) in pathogenesis of neurological diseases is growing. This includes ongoing research exploring the potential therapeutic targets involving the androgen signaling pathway for management of neurological disorders. Future placebo-controlled clinical trials are essential to determine the efficacy and safety of TRT or androgen-blocking therapies in managing neurological disease.

Purpose of review: To evaluate the impact of systemic comorbidities on outcomes following endovascular thrombectomy (EVT) for acute ischemic stroke.

Recent findings: Although EVT achieves high rates of large-vessel reperfusion, clinical outcomes are significantly influenced by underlying comorbidities. Chronic hypertension impairs collateral circulation and increases the risk of cerebral edema and mortality. Diabetes mellitus is associated with reduced functional recovery and heightened hemorrhagic risk. Atrial fibrillation often leads to larger infarcts and contributes to higher unadjusted mortality. Chronic kidney disease, particularly in patients with dialysis dependence, predicts poor neurological outcomes and increased procedural complications. Active malignancy substantially elevates mortality, especially in patients with metastatic disease. Systemic comorbidities are important modifiers of outcome after EVT. While technical success rates routinely exceed 80-90%, functional recovery and survival vary significantly across patient subgroups. Meta-analyses and registry data highlight that comorbidities independently increase the risk of futile recanalization, complications, and mortality. EVT remains appropriate for medically complex patients, but optimal results require comorbidity-informed risk stratification and multidisciplinary, goal-concordant care.

Purpose of review: Diabetes is a well-established risk factor for stroke. Understanding the pathophysiology of this connection is crucial to implementing appropriate prevention strategies. Lately, there has been a paradigm shift in the care of individuals with diabetes toward the use of glucose-lowering medications with potential cardiovascular, cerebrovascular or cardiorenal benefits. The aim of this article is to provide a critical analysis of the role of diabetes in cerebrovascular disease and current evidence and recommendations for the use of glucose-lowering medication with particular focus on the sodium glucose cotransporter-2 inhibitor (SGLT2i) class.

Recent findings: Intensive glycemic control in individuals with diabetes reduces the risk of microvascular complications, but there is less clear evidence for decreasing risk of macrovascular events (e.g., stroke). A multifaceted management of diabetes addressing healthy lifestyle practices, glycemic control, and optimization of other cardiovascular risk factors is highly recommended. SGLT2i are the latest class of antihyperglycemic agents available for diabetes management. Canagliflozin and empagliflozin are associated with reduction in major adverse cardiovascular events (MACE). Dapagliflozin did not reduce the rate of MACE but is associated with reduction in heart-failure related death and hospitalization and has the potential to decrease dementia risk. Ertugliflozin decreases rates of hospitalization related to heart failure however it was non-inferior to placebo in reducing MACE. There is increasing evidence that the use of SGLT2i may reduce the risk of stroke, particularly hemorrhagic stroke, in individuals with type 2 diabetes and a high risk of cardiovascular events, and that SGLT2i may also be beneficial for brain health by decreasing risk of cognitive decline and dementia. Antihyperglycemic therapy should be tailored to patients' circumstances. SGLT2i treatment should be considered in patients with type 2 diabetes and established or high-risk cardiovascular disease, heart failure, or chronic kidney disease, to reduce the overall cerebro-cardiovascular and renal risks.

Purpose: Stroke is a leading cause of disability and mortality worldwide. It has been estimated that more than 90% of the risk of stroke is associated with modifiable factors, including diabetes, hypertension, obesity, and heart disease. Glucagon-like peptide 1 receptor agonists (GLP1RAs) have been shown to have a beneficial effect on these major risk factors. In this review, we discuss the evidence supporting the use of GLP1RAs on brain health, particularly in relation to stroke prevention.

Recent findings: The results of multiple randomized clinical trials demonstrate that, among patients with type 2 diabetes, GLP1RAs reduce body weight and improve glucose levels and lipid metabolism. In high-risk populations, GLP1RAs also reduce the risk of major adverse cardiovascular events, including all stroke and non-fatal stroke. Mechanistically, GLP1RAs have a beneficial effect on different stroke risk factors, support microvascular function, and reduce inflammation and oxidative stress. GLP1RAs are recommended for the primary prevention of stroke in patients with diabetes and elevated cardiovascular risk.

Purpose of review: Genetic factors play an important contribution to the aetiology of epilepsy and may have implications for management. Whilst the study of monogenic epilepsies has predominantly centred around children, there is a critical need to understand the burden of monogenic epilepsies in adults. This understanding is essential to steer the application of genetic testing and to facilitate access to gene-driven therapies in adults with epilepsy.

Recent findings: The yield of diagnostic genetic testing in adults with epilepsy and neurodevelopmental disorders is similar to that in children (ranging from 23-50%). Distinct causal genes underlie the most common monogenic epilepsies identified in adulthood compared to childhood, although SCN1A is the most commonly implicated gene across both populations. Genetic diagnoses made in adults with epilepsy frequently have direct implications for clinical management. However, very few gene-driven therapies are supported by evidence from formal studies. Genetic testing should be considered in adults with unexplained epilepsy and may have important implications for management, including the potential for gene-driven therapies. However, further work is needed to understand the outcomes of gene-driven therapies in adults with epilepsy.

Purpose of review: Artificial intelligence (AI) promises to compress stroke treatment timelines, yet its clinical return on investment remains uncertain. We interrogate state‑of‑the‑art AI platforms across imaging, workflow orchestration, and outcome prediction to clarify value drivers and execution risks.

Recent findings: Convolutional, recurrent, and transformer architectures now trigger large‑vessel‑occlusion alerts, delineate ischemic core in seconds, and forecast 90‑day function. Commercial deployments-RapidAI, Viz.ai, Aidoc-report double‑digit reductions in door‑to‑needle metrics and expanded thrombectomy eligibility. However, dataset bias, opaque reasoning, and limited external validation constrain scalability. Hybrid image‑plus‑clinical models elevate predictive accuracy but intensify data‑governance demands. AI can operationalize precision stroke care, but enterprise‑grade adoption requires federated data pipelines, explainable‑AI dashboards, and fit‑for‑purpose regulation. Prospective multicenter trials and continuous lifecycle surveillance are mandatory to convert algorithmic promise into reproducible, equitable patient benefit.

Purpose of review: This review aims to evaluate recent advances in large core stroke management with a focus on diagnostic imaging protocols to select patients for endovascular therapy.

Recent findings: Recent randomized controlled trials have shown that thrombectomy can lead to favorable outcomes in patients with large infarcts, contradicting previous assumptions that thrombectomy was not indicated in such patients due to higher risks and very low benefits. Although mechanical thrombectomy remains the gold standard of medical treatment for large vessel occlusions with demonstrated salvageable brain tissue, analysis of the results of recent randomized trials in patients with large ischemic stroke should help us expand patient selection, optimize timing, and explore different management modalities to improve the outcomes of therapy in these patients.