Current Opinion in Neurology最新文献

Purpose of review: Rare gliomas, including circumscribed astrocytic, glioneuronal, and neuronal central nervous system (CNS) tumours, though collectively uncommon, present significant clinical challenges due to their heterogeneity and limited therapeutic evidence. Conventional management has relied predominantly on surgery and radiotherapy. Advances in molecular profiling have revealed actionable targets, prompting a timely reassessment of treatment paradigms. This review aims to describe current standard treatments and recent advances in molecularly targeted approaches for rare gliomas.

Recent findings: Gross total surgical resection remains the primary therapeutic modality for rare gliomas, providing optimal tumour control and symptom relief. Radiotherapy offers additional benefit in case of subtotal resection or recurrent disease, particularly in WHO grade 3 tumours. In contrast, conventional chemotherapy has shown limited efficacy and is typically reserved for refractory or progressive cases.The discovery of actionable molecular alterations in a substantial subset of rare gliomas has led to increasing integration of targeted therapies into clinical management. Notable recent advances include the use of BRAF/MAPK pathway inhibitors (e.g., dabrafenib/trametinib, tovorafenib), NTRK inhibitors (e.g., larotrectinib, entrectinib), FGFR inhibitors (e.g., erdafitinib, pemigatinib), and mTOR inhibitors (e.g., everolimus), which have demonstrated meaningful clinical activity in select patient populations.

Summary: Precision oncology is rapidly transforming the treatment landscape for rare CNS tumours. Integration of targeted therapies into clinical protocols - ideally guided by multidisciplinary molecular tumour boards - is increasingly warranted. Future research must optimise timing, combination strategies, and overcome resistance, while new biomarkers and liquid biopsy tools are needed to guide the choice of therapy and monitor response in this underserved population.

Purpose of review: To summarize the role of diagnostic amino acid PET in the era of checkpoint inhibitors and targeted therapies for brain tumor treatment.

Recent findings: Amino acid PET, particularly O -(2-[ 18 F]-fluoroethyl)-L-tyrosine (FET) PET, has shown promise in distinguishing treatment-related changes such as pseudoprogression and pseudoresponse from true tumor relapse in patients receiving immunotherapy or targeted therapies for brain metastases and gliomas, often outperforming conventional MRI. Additionally, serial amino acid PET imaging has demonstrated potential in early response assessment following these agents.

Summary: Larger prospective trials with a higher number of patients are still needed to validate the clinical impact of amino acid PET when immunotherapy or targeted therapies are used for brain tumor therapy.

Purpose of review: This review provides a summary of recent literature concerning neurocognitive functioning (NCF) in patients with glioma, including developments in assessment and characterization of NCF impairment, understanding of etiologic contributors, and mitigation and intervention strategies.

Recent findings: NCF impairment remains ubiquitous in patients with glioma, despite recognition of the detrimental impact upon well being. Risk factors for NCF decline and the underlying neurophysiologic mechanisms continue to be unraveled, including individual genetic characteristics, dynamic tumor and treatment-related changes to local and whole-brain networks, inflammatory cascades, and influence of social determinants of health. Developments in glioma treatment may improve NCF outcomes, such as advances in brain mapping for safer resection and investigational approaches to radiation delivery, though evidence is largely preliminary. While traditional neuropsychological testing has demonstrated utility in this population, digital and other emerging assessment approaches require further study. Additionally, few strategies for management and rehabilitation of NCF impairment are well supported, though potentially efficacious intervention approaches are briefly highlighted.

Summary: Impairment of NCF arises from complex tumor and treatment-driven network injury. While development of management strategies has been relatively modest, future approaches may capitalize on the rapidly advancing understanding of etiological mechanisms underlying NCF impairment in patients with glioma.

Purpose of review: Gliomas with mutations in the gene for isocitrate dehydrogenase (IDH) display a unique immune microenvironment that is distinct from IDH-wildtype gliomas. This unique immune microenvironment is shaped by 2-hydroxyglutarate (2-HG), an oncometabolite produced by mutant IDH. These features provide an opportunity to develop and test targeted immunotherapies for IDH-mutant gliomas.

Recent findings: IDH-mutant gliomas are characterized by an immunosuppressive tumor immune microenvironment (TIME) that suppresses the infiltration and activation of tumor-specific T cells. This is owed both to direct effects of the oncometabolite 2-hydroxyglutarate on glioma-infiltrating T cells and myeloid cells and indirect effects on the chemotactic profile of tumor cells. These immunosuppressive effects are reversed by IDH inhibitors recently approved for the treatments of IDH-mutant gliomas. At the same time, clinical trials have demonstrated encouraging results for targeted immunotherapies using vaccines targeting the most frequent mutation IDH1R132H.

Summary: The reversal of the immunosuppressive effects by IDH inhibitors has opened exciting avenues for combinatorial immunotherapies such as vaccines and immune checkpoint inhibitors.

Purpose of review: Spinal cord injury (SCI) remains a disabling condition associated with long term neurological impairment, functional disability, and reduced quality of life. Despite decades of research, pharmacological interventions with proven clinical efficacy remain limited. This review critically evaluates the current evidence supporting riluzole as a neuroprotective agent for acute traumatic and nontraumatic SCI. We synthesize findings from preclinical and clinical studies, assess the progress towards clinical translation, and outline key challenges and research opportunities for future implementation.

Recent findings: Riluzole, an FDA-approved agent for amyotrophic lateral sclerosis (ALS), inhibits voltage-gated sodium channels and modulates glutaminergic transmission, two mechanisms central to the pathogenesis of secondary injury in SCI and in nerve cell degeneration in nontraumatic forms of SCI, including degenerative cervical myelopathy (DCM). Preclinical studies consistently demonstrate functional and histopathological improvements following riluzole administration. Phase I/II trials have provided evidence for its safety and tolerability in acute SCI patients, while the RISCIS and CSM-PROTECT trials, two landmark multicenter randomized controlled studies, along with their secondary analyses, revealed promising multidomain improvements in motor function, independence, and quality of life indices. Sub-studies have also established pharmacokinetic and pharmacodynamic frameworks for individualized dosing, and early biomarker analysis suggests potential for predictive stratification.

Summary: Riluzole represents a promising candidate for neuroprotection in traumatic and nontraumatic SCI. The consistency of favorable trends across multiple domains and strong support from preclinical studies highlight riluzole's value in orphan diseases such as SCI. Future directions should focus on refining the therapeutic window, optimizing PK/PD modeling, and identifying patient subgroups most likely to benefit. Its implementation in a multimodal treatment paradigm for acute SCI will be crucial for optimizing management protocols in this highly disabling condition.

Purpose of review: Traumatic spinal cord injury (tSCI) is a devastating neurological emergency with high morbidity and no proven therapies that reliably improve recovery. While early decompression and hemodynamic optimization are standard, clinicians lack imaging tools to stratify injury severity or monitor physiological responses in real time. Advances in high-resolution B-mode, contrast-enhanced ultrasound, and multiparametric approaches offer a unique opportunity to close this gap and improve patient-specific treatment strategies.

Recent findings: Ultrasound can: characterize injury morphology, revealing cord swelling, hemorrhage, and parenchymal disruption; verify and optimize cord decompression by visualizing restoration of the subarachnoid space, and cerebrospinal fluid pulsatility; assess cord perfusion in real time with contrast-enhanced ultrasound, and guide targeted interventions in acute and chronic tSCI, including therapeutic delivery, blood-spinal cord barrier modulation, and neuromodulation. Preclinical models and early clinical series increasingly validate these applications.

Summary: Integrating ultrasound into tSCI care could yield actionable biomarkers, enhance intraoperative and critical care decision-making, and accelerate the translation of novel therapies. Future priorities include standardizing imaging protocols, validating prognostic metrics, correlating imaging findings with long-term outcomes, and developing portable systems for continuous, patient-specific monitoring.

Purpose of review: Purpose of this review is to highlight the recent findings in terms of clinical aspects, pathogenic mechanisms and managements of statin associated muscle symptoms (SAMS), and focusing on the use of novel therapeutic alternatives in clinical practice.

Recent findings: While extensive research has been conducted on SAMS, the precise mechanisms remain unclear. Recent findings continue to explore various aspects, including potential risk factors, diagnostic approaches, and management strategies. Managing SAMS involves a careful assessment to confirm the diagnosis, a stepwise approach to treatment that may include dose adjustments, switching statins, considering alternate-day dosing, and exploring nonstatin therapies, all while prioritizing patient well being and cardiovascular risk reduction through shared decision-making and ongoing monitoring. In recent years, the therapeutic landscape has expanded with the introduction of several novel lipid-lowering agents, providing valuable alternatives for both statin-tolerant and statin-intolerant patients but their use in clinical practice is still limited because of high costs, regulatory limitations and type of administration.

Summary: Given the increasing use of both traditional and emerging lipid-lowering therapies, a clear understanding of their comparative safety, particularly regarding musculoskeletal adverse effects, is essential for guiding clinical decision-making.

Purpose of review: To review the clinical trial results and emerging real-world data of two new enzyme replacement therapies (ERTs) for late-onset Pompe disease and to compare these effects in the context of what has been achieved over the last two decades in advancing care for Pompe disease.

Recent findings: Randomized controlled trials (RCTs) of avalglucosidase alfa and cipaglucosidase alfa plus miglustat have demonstrated that both treatments are at least as efficacious as alglucosidase alfa and possess a comparable safety profile. Several post hoc analyses of the trial data have shown that these newer ERTs result in a greater percentage of patients achieving meaningful improvements and larger reductions in biomarker levels. The first real-world data on switching from alglucosidase alfa to avalglucosidase alfa has shown that the switch is safe and may alter individual disease trajectories.

Summary: The advent of two next-generation enzyme replacement therapies marks a new era in treating patients diagnosed with Pompe disease. Clinical trials and early real-world data suggest that they may be superior to alglucosidase alfa, the standard of care for the past 20 years, although head-to-head comparisons between all three treatments are lacking. More data will become available over the next 5 years, leading to better guidelines for starting, stopping and switching therapies based on a more personalized assessment of outcomes.