Current Opinion in Neurology最新文献

Purpose of review: This article discusses commonly encountered medical and neurological complications in patients with brain tumors and highlights recommendations for their management based on updated evidence.

Recent findings: Use of dexamethasone is correlated with worse prognosis in patients with glioblastoma, and in brain metastases, high doses may lead to increased side effects without additional clinical benefit. There are multiple antiseizure medications (ASM) to choose from and possible interactions and toxicity must be considered when choosing an agent. Additionally, there is growing interest in the use of AMPA receptor blockers as ASM in patients with brain tumors. Nonpharmacological strategies for the management of fatigue remain paramount. Cognitive decline is common after whole brain radiation (WBRT) and hippocampal-sparing WBRT results in superior cognitive outcomes. Venous thromboembolism is a common complication and there is growing evidence on the use of direct oral anticoagulants (DOACs) in this population.

Summary: There is evolving evidence on the management of medical and neurological complications in patients with brain tumors. These complications, require early identification and multidisciplinary collaboration and expertise.

Purpose of review: Cognitive impairment is one of the most challenging non-motor symptoms of Parkinson's disease (PD) and may occur during all PD stages. There are no established pharmacological treatments for PD-related cognitive impairment, which may be improved by cognition-based interventions (i.e., cognitive stimulation, cognitive training, cognitive rehabilitation). Multimodal cognition-based interventions by adjunctive drugs, exercise, non-invasive brain stimulation and technologies may be effective in PD.

Recent findings: Exercise combined with cognitive training may enhance global, memory, visuospatial and executive functioning, transcranial direct current stimulation delivered alongside cognitive training may improve attention and executive functioning, and exergames, semi-immersive virtual reality (VR) and telerehabilitation plus non-immersive VR combined with cognitive training may ameliorate global and executive functioning in PD patients.

Summary: The evidence reviewed here, despite preliminary, is very encouraging and suggests strong rationale for combining pharmacological and non-pharmacological interventions with cognition-based treatments in PD. To overcome limitations of current studies, we propose some recommendations for future trials on drugs, exercise, non-invasive brain stimulation and technologies combined with cognition-based treatments for cognitive impairment in PD.

Purpose of review: While wearable robotics is expanding within clinical settings, particularly for neurological rehabilitation, there is still a lack of consensus on how to effectively assess the performance of these devices. This review focuses on the most common metrics, whose selection and design are crucial for optimizing treatment outcomes and potentially improve the standard care.

Recent findings: The literature reveals that while wearable robots are equipped with various embedded sensors, most studies still rely on traditional, nontechnological methods for assessment. Recent studies have shown that, although quantitative data from embedded sensors are available (e.g., kinematics), these are underutilized in favor of qualitative assessments. A trend toward integrating automatic assessments from the devices themselves is emerging, with a few notable studies pioneering this approach.

Summary: Our analysis suggests a critical need for developing standardized metrics that leverage the data from embedded sensors in wearable robots. This shift could enhance the accuracy of patient assessments and the effectiveness of rehabilitation strategies, ultimately leading to better patient outcomes in neurological rehabilitation.

Purpose of review: Current biological findings provide new insights into the genetics driving growth of low-grade gliomas in pediatric patients. This has provided new targets for novel therapies. The purpose of this paper is to review novel therapies for pediatric low-grade gliomas that have been published in the past 24 months.

Recent findings: Low-grade gliomas are often driven by mitogen activated protein kinase (MAPK) alterations either with BRAF V600E point mutations or BRAF fusions. Current advances have also highlighted novel fusions of fibroblast growth factor receptor (FGFR), myeloblastosis family of transcription factors (MYB), meningioma 1 tumor suppressor (MN1), neurotrophic receptor kinase family of receptors (NTRK), Kristen RAS (Rat Sarcoma Virus) oncogene homolog in mammals (KRAS), Receptor tyrosine kinase ROS proto oncogene 1 (ROS1), protein kinase C alpha (PRKCA), and platelet derive growth factor receptor (PDGFR) amplification. Novel therapies have been employed and are showing encouraging results in pediatric low-grade gliomas. Current trials are underway with newer generation pan RAF inhibitors and mitogen activated protein kinase - kinase (MEK) inhibitors. Other early phase clinical trials have provided safety data in pediatric patients targeting FGFR fusion, NTRK fusion, PDGFR amplification and ROS1 mutations.

Summary: Historical treatment options in pediatric low-grade gliomas have utilized surgery, radiation therapy and conventional chemotherapy. Recently greater insight into their biology has found that alterations in MAPK driven pathways are often the hallmark of tumorigenesis. Targeting these novel pathways has led to tumor control and shrinkage without the use of conventional chemotherapy. Caution should be taken however, since these treatment options are still novel, and we do not fully appreciate the long-term effects. Nonetheless a new era of targeted medicine is here.

Purpose of review: To review the landscape of chimeric antigen receptor T-cell (CAR T) therapy for gliomas as seen in recently published trials and discuss on-going challenges with new cancer immunotherapy treatments.

Recent findings: Given how CAR T therapy has revolutionized the treatment of several hematologic malignancies, there has been increasing interest in using immunotherapy, and particularly CAR T therapy for gliomas. Within the past decade, several first in human trials have published early patient experiences showing treatment is generally well tolerated but with limited efficacy, which may be improving with newer evolutions in CAR T design to overcome known resistance mechanisms in glioma treatment.

Summary: CAR T therapy is a promising avenue of treatment for high-grade gliomas, which have a universally poor prognosis as well as limited therapeutics. There are a growing number of CAR T clinical trials for CNS tumors and thus, an understanding of their treatment strategies, toxicity management, and overcoming resistance mechanisms will be important for both clinical practice and to identify areas for future research.

Purpose of review: The purpose of this review is to discuss the value of blood and CSF biomarkers in primary CNS tumors.

Recent findings: Several analytes can be assessed with liquid biopsy techniques, including circulating tumor cells, circulating cell-free tumor DNA, circulating cell-free RNA, circulating proteins and metabolites, extracellular vesicles and tumor-educated platelets. Among diffuse gliomas of the adult, ctDNA in blood or CSF has represented the most used analyte, with the detection of molecular alterations such as MGMT promoter, PTEN, EGFRVIII, TERT promoter mutation and IDH R132H mutation. In general, CSF is enriched for ctDNA as compared with plasma. The use of MRI-guided focused ultrasounds to disrupt the blood-brain barrier could enhance the level of biomarkers in both blood and CSF. The detection of MYD88 L265P mutation with digital droplet PCR and the detection of ctDNA with next generation sequencing represent the best tools to diagnose and monitoring CNS lymphomas under treatment. In meningiomas, the low concentration of ctDNA is a limiting factor for the detection of driver mutations, such as NF2, AKTs, SMO, KLF4, TRAF7, SMARCB1, SMARCE1, PTEN, and TERT; an alternative approach could be the isolation of ctDNA through circulating extracellular vesicles. Liquid biopsies are being used extensively for diagnosis and surveillance of diffuse midline gliomas, in particular with the detection of the driver mutation H3K27M. Last, specific methylome patterns in CSF may allow the distinction of glioblastomas from CNS lymphomas or meningiomas.

Summary: This review summarizes the current knowledge and future perspectives of liquid biopsy of blood and CSF for diagnosis and monitoring of primary CNS tumors.

Purpose of review: Brain tumor treatment presents challenges for patients and clinicians, with prognosis for many of the most common brain tumors being poor. Focused ultrasound (FUS) can be deployed in several ways to circumvent these challenges, including the need to penetrate the blood-brain barrier and spare healthy brain tissue. This article reviews current FUS applications within neuro-oncology, emphasizing ongoing or recently completed clinical trials.

Recent findings: Most clinical interest in FUS for neuro-oncology remains focused on exploring BBB disruption to enhance the delivery of standard-of-care therapeutics. More recently, the application of FUS for radiosensitization, liquid biopsy, and sonodynamic therapy is garnering increased clinical attention to assist in tumor ablation, early detection, and phenotypic diagnosis. Preclinical studies show encouraging data for the immunomodulatory effects of FUS, but these findings have yet to be tested clinically.

Summary: FUS is a burgeoning area of neuro-oncology research. Data from several forthcoming large clinical trials should help clarify its role in neuro-oncology care.

Purpose of review: This review highlights recent developments in noninvasive brain stimulation (NIBS) techniques and applications for improving motor outcomes after stroke. Two promising areas of development relate to deep brain neuromodulation and the use of single-pulse transcranial magnetic stimulation (TMS) within a prediction tool for predicting upper limb outcome for individual patients.

Recent findings: Systematic reviews highlight the inconsistent effect sizes of interventional NIBS for motor outcome after stroke, as well as limited evidence supporting the interhemispheric competition model. To improve the therapeutic efficacy of NIBS, studies have leveraged metaplasticity and priming approaches. Transcranial temporal interference stimulation (tTIS) and low-intensity focused ultrasound stimulation (LIFUS) are emerging NIBS techniques with potential for modulating deeper brain structures, which may hold promise for stroke neurorehabilitation. Additionally, motor evoked potential (MEP) status obtained with single-pulse TMS is a prognostic biomarker that could be used to tailor NIBS for individual patients.

Summary: Trials of interventional NIBS to improve stroke outcomes may be improved by applying NIBS in a more targeted manner. This could be achieved by taking advantage of NIBS techniques that can be targeted to deeper brain structures, using biomarkers of structural and functional reserve to stratify patients, and recruiting patients in more homogeneous time windows.