Current Opinion in Neurology最新文献

Purpose of review: Chimeric antigen receptor (CAR) T-cell therapies are increasingly used in hematologic malignancies and are now being investigated in autoimmune disorders. This review aims to summarize the spectrum of neurological complications associated with CAR-T.

Recent findings: While early-onset neurotoxicity is well characterized, other neurological syndromes are increasingly reported. Neurological complications can be provisionally classified into three categories: early-onset immune effector cell-associated neurotoxicity syndrome (ICANS); delayed-onset neurological syndromes specific to single CAR T-cell types; and tumour inflammation-associated neurotoxicity (TIAN). Other postinfusion neurological syndromes have also been observed but with uncertain links to CAR T-cells. Management must be tailored to preserve both neurological function and CAR T-cell efficacy. Ongoing efforts target biomarker development, and risk-adapted strategies, especially in steroid-refractory cases.

Summary: As CAR T-cell indications broaden, clinicians must recognize diverse neurological toxicities and implement individualized, evidence-based interventions to improve neurological outcomes.

Purpose of review: Spinal cord injury (SCI) causes profound gait impairment and autonomic dysfunction. Deep brain stimulation (DBS) of supraspinal locomotor centers may strengthen spared descending motor and autonomic pathways to improve walking. Preclinical and clinical studies have targeted the cuneiform nucleus (CnF) and pedunculopontine nucleus (PPN) of the mesencephalic locomotor region (MLR) and the lateral hypothalamus. To summarize recent progress in DBS as a strategy to facilitate locomotion with a particular focus on SCI.

Recent findings: DBS of the CnF, PPN, and lateral hypothalamus enhances gait and cardiorespiratory function in animal models and early human trials. Directional electrodes and individualized programming appear to reduce risks and optimize efficacy. Evidence suggests DBS can amplify supraspinal command circuits, supporting locomotor facilitation after injury.

Summary: DBS of MLR and lateral hypothalamus circuits represent a promising therapeutic approach for gait recovery in SCI. Key priorities for future clinical trials include stratification by injury severity, monitoring of autonomic outcomes, and assessment of long-term effects on mobility and quality of life. Integration with physiotherapy may further augment recovery. Collectively, current findings support DBS as an emerging intervention to restore locomotor function following SCI. The use of DBS for motor recovery after SCI is investigational.

Purpose of review: In this review, we discuss electrical and optogenetic technologies for stimulating the spinal cord to improve movement after spinal cord injury (SCI).

Recent findings: Paralysis or paresis following SCI severely impairs control and movement of the extremities. Restoring movement in the upper and lower extremities is a top priority for this population. Invasive and noninvasive electrical stimulation of the spinal cord can modulate the activity of spinal circuits, resulting in improvements in motor and sensory function. More recently, optogenetic stimulation has emerged as another technique capable of modulating spinal circuity to facilitate movement recovery in animal models. Recent studies are offering new insights into the effects of parameter selection, multisite stimulation, and the combined effects of stimulation and wearable robotic exoskeletons, all with the goal of restoring movement after SCI.

Summary: Modulating the activity of the spinal cord via electrical and optogenetic stimulation is a promising intervention for improving movement after SCI. Future studies should determine optimal stimulation parameters, synergistic effects when combined with wearable robotics, and the safety of optogenetics in the human spinal cord. Such work will best position these emerging technologies for clinical translation.

Purpose of review: Spinal cord stimulation (SCS) for pain control and movement recovery have developed under parallel conceptual frameworks. SCS for pain has traditionally targeted the dorsal columns, while SCS for movement recovery has targeted the large-diameter afferent fibers near the dorsal root entry zone. We review the evidence to support these parallel mechanistic frameworks and explore potential mechanistic overlap between the two fields.

Recent findings: Recent advances in closed-loop stimulation for pain and dorsal root (DR) stimulation for movement recovery speak to the value of these parallel mechanistic models in each field. However, review of the devices, electrode placement, and stimulation parameters used in both fields reveals overlap in the doses of SCS considered effective in each. Furthermore, evidence from finite element modeling suggests overlapping recruitment of dorsal column and dorsal root fibers from both midline and lateral stimulation.

Summary: There is evidence to support overlapping mechanisms of SCS for pain and movement recovery. The implications of potential mechanistic overlap warrant further investigation.

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.