Current Opinion in Neurology最新文献

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.

Purpose of review: Myofibrillar myopathies (MFMs) are traditionally defined by histopathology, but recent genetic discoveries have broadened the spectrum of causative genes beyond Z-disk components. This review aims to address the resulting terminological inconsistency by proposing a refined, mechanism-based definition of MFM centered on its identity as a "Z-disk-opathy." This re-evaluation is timely and relevant for improving diagnostic clarity and guiding future research.

Recent findings: The literature increasingly reports MFM-like pathology in conditions caused by mutations in genes not directly encoding Z-disk structural proteins or their interacting chaperones. This review highlights the pathogenic mechanisms distinguishing true MFMs, which involve disruption of Z-disk protein structure or Z-disk protein homeostasis, from "myopathies with MFM pathology" that share histological features but stem from different molecular etiologies. Key themes include the dominant nature of mutations in Z-disk structural proteins and the critical role of chaperone dysfunction in MFM pathogenesis.

Summary: A refined definition classifying MFM as a "Z-disk-opathy" offers a clearer framework for diagnosis and mechanistic understanding. This distinction has significant implications for clinical practice, facilitating more accurate diagnosis, and for research, by supporting the development of targeted therapeutic strategies aimed at either restoring Z-disk proteostasis or mitigating the effects of aberrant protein accumulation.

Purpose of review: Small fiber neuropathies (SFN) are a heterogeneous group of disorders affecting the thinly myelinated Aδ and unmyelinated C-fibers. The clinical picture is dominated by neuropathic pain, often accompanied by autonomic symptoms of variable severity. The underlying causes encompass metabolic conditions like diabetes mellitus, immuno-mediated disorders, infection, exposure to toxins, and gain-of-function variants in the genes encoding the Nav1.7, Nav1.8, and Nav1.9 sodium channel subunits, though the list of associated diseases continues to grow. Recently, increased attention has focused on immune-mediated forms, which led to the identification of potentially treatable subgroups. These discoveries have advanced our understanding of pathophysiological mechanisms.

Recent findings: Recent studies have broadened the spectrum of underlying conditions associated with SFN, including immune-mediated forms and links to SARS-CoV-2 infection and vaccines. Studies on genetic variants linked to unique clinical presentations have also yielded new insights. Furthermore, emerging perspectives highlighted disorders involving small fiber pathology that lacks typical clinical features of neuropathic pain, challenging traditional diagnostic criteria.

Summary: Deepening our understanding of the causes underlying SFN advances the identification of potential therapeutic targets. The clinical presentation of SFN can vary significantly and may not consistently correlate with specific underlying conditions. Therefore, a systematic investigation of possible causes through a structured diagnostic assessment is critical to unveil additional contributing factors.

Purpose of review: This review summarizes recent evidence on sleep disturbances in amyotrophic lateral sclerosis (ALS), emphasizing their role as intrinsic features of the disease process rather than consequence of motor decline.

Recent findings: Emerging data suggest that sleep disturbances such as sleep fragmentation, rapid eye movement sleep (REM) and non rapid eye movement sleep (NREM) alterations and circadian changes often precede classic motor symptoms. Structural and functional hypothalamic changes have been observed in early ALS, suggesting a direct role in sleep-wake dysregulation. In addition, impaired glymphatic clearance during sleep may contribute to neurodegeneration by impairing the removal of protein waste. Polysomnographic studies and cohort data support the presence of prodromal sleep abnormalities in both symptomatic patients and gene mutation carriers. Noninvasive ventilation has shown benefits not only in respiratory management but also in improving sleep quality and overall prognosis.

Summary: Sleep alterations in ALS are increasingly recognized as early indicators and potential modulators of disease progression. The hypothalamus and the glymphatic system emerge as key contributors to these disturbances, highlighting sleep as a therapeutic target. Understanding the role of sleep in ALS pathophysiology may aid in earlier diagnosis and novel intervention strategies aimed at modifying disease course.

Purpose of review: Guillain-Barré syndrome (GBS) is a severe but treatable form of immune-mediated neuropathy. The purpose of this review is to provide an update on current immune treatments for GBS, highlight challenges in clinical practice and research, and discuss new developments in therapies that focus on reducing inflammation and preventing further nerve damage.

Recent findings: In 2023, a GRADE-based guideline was published on the diagnosis and treatment of GBS on behalf of EAN/PNS. Several clinical trials have been conducted in GBS recently, including studies with an observational comparative study design.

Summary: Since 30 years, intravenous immunoglobulins and plasma exchange are the only proven effective immune treatments for GBS. Despite these treatments, a substantial proportion of patients recover incompletely and have residual disability or complaints with a high impact on quality of life. New treatment trials focus on reducing immunoglobulin G antibodies to nerves and inhibition of complement activation. Observational comparative studies based on extensive and well defined cohorts are an alternative method to evaluate the effect of treatments in GBS. Several novel study designs are discussed that aim to facilitate the conduct of future trials with more sustainable use of data.

Purpose of review: Autoimmune nodopathies (AN) are a recognized distinct group of immune-mediated peripheral neuropathies with unique immunopathological features and therapeutic implications. This review synthesizes recent advances in their pathogenesis, diagnosis, and management, which have refined their clinical classification and informed targeted treatment strategies.

Recent findings: AN are characterized by autoantibodies targeting surface proteins in the nodal-paranodal area (anti-contactin-1, anti-contactin-associated protein 1, anti-neurofascin-155, anti-pan-neurofascin), predominantly of IgG4 subclass. Recent studies have delineated antibody subclass contributions to disease mechanisms and identified B-cell response patterns predictive of therapeutic outcomes. Despite clinical overlap with chronic inflammatory demyelinating polyradiculoneuropathy and Guillain-Barré syndrome, AN exhibit a distinct phenotype and a poor response to intravenous immunoglobulins. Multiple studies, including recent ones, report good response and long-term clinical remission with B-cell depleting therapies. Diagnostic assays such as cell-based assays and ELISA offer high accuracy, while biomarker-guided monitoring using antibody titers and serum neurofilament light chain supports individualized follow-up.

Summary: Emerging evidence consolidates AN as a nosologically and therapeutically distinct entity. Integration of immunopathological insights with biomarker-driven strategies enables precision diagnostics and targeted immunotherapy, improving clinical outcomes.