Expert Review of Neurotherapeutics最新文献

Introduction: Medulloblastoma (MB) represents the most prevalent malignant pediatric brain tumor. Although survival has greatly improved, the tumor and its treatments have devastating long-term side effects that negatively impact quality of survival. Consequently, there is a critical need for innovative therapeutic strategies aimed at enhancing patient outcomes and mitigating treatment-related toxicities.

Areas covered: In this review, the authors summarize the current evidence regarding metronomic chemotherapy (MC) and drug repurposing in MB and discuss prospective future developments by searching the PubMed database from 1980 to 2025. Drug repurposing (DR), defined as the identification of novel therapeutic applications for existing pharmacological agents, presents a promising strategy to expedite the development of effective and well-tolerated treatments. Metronomic chemotherapy, characterized by the frequent administration of low-dose chemotherapeutic agents, exerts its therapeutic effects by targeting the tumor microenvironment and angiogenesis. Notably, metronomic chemotherapy, particularly in multidrug combinations incorporating repurposed agents, has demonstrated significant clinical activity in patients with relapsing/refractory MB.

Expert opinion: Data on MC and DR, published over the past decades, has confirmed their potential to prolong survival and potentially cure patients with refractory/relapsing MB. Randomized trials are now mandatory to generate higher levels of evidence.

Introduction: Despite traditional workups, accurate diagnosis of patients who are classified under cryptogenic stroke with underrecognized etiologies is very challenging. Accurate diagnosis is important for timely and optimized treatment modalities, disease progression monitoring, and proper treatment assessment.

Areas covered: This review highlights the limitations regarding the diagnosis of ischemic stroke with underrecognized etiologies and discusses the novel technologies that can shape the future diagnosis with personalized medicine approach. The current article is based on English language research articles selected from PubMed, EMBASE, Scopus, Web of Science search using the following search terms: embolic stroke of undetermined source, cryptogenic stroke, atrial cardiopathy, PFO closure, cancer-associated stroke, wearable devices, multiomics, stroke and artificial intelligence.

Expert opinion: Soon, extended diagnostic workups, multiomics, wearable and implantable technologies, and novel imaging techniques will become more common in routine diagnosis of ischemic stroke. The integration of novel technologies supported by artificial intelligence will transform stroke management with rapid and precise diagnosis and individualized treatment strategies. This will put future diagnosis in the hands of patients and the gradual integration of the novel technologies may provide real-time, patient-specific stroke management options.

Background: Serotonin Reuptake Inhibitors (SRIs) are the first-line pharmacotherapy for obsessive-compulsive disorder (OCD), but they are effective in only 40-60% of the patients. We performed meta-analyses of predictors of resistance to SRIs in OCD.

Methods: The systematic review was conducted as per PRISMA guidelines and registered in PROSPERO (ID: CRD42024568797). Multiple random-effects meta-analyses were performed for each predictor, depending on the type of the predictor variable and the outcome (continuous vs categorical). Pooled outcomes were reported as odds ratios (OR), mean differences (MD), standardized mean differences (SMD), Fisher's r-to-z transformed correlation coefficient, along with their 95% confidence intervals (CI).

Results: Out of 10,688 studies screened, 46 met our eligibility criteria, including a total of N = 4860 subjects. Analysis of categorical outcomes showed that earlier age at onset (SMD = 1.9 [0.79-2.99]), longer duration of illness (SMD = 2.78 [0.77-4.79]), greater OCD severity at baseline (MD = 2.50 [1.53-3.46]), poorer insight (OR = 0.24 [0.08-0.68]), contamination obsessions (OR = 0.61 [0.43-0.85]), and comorbid tics (OR = 0.44 [0.29-0.67]) predicted non-response to SRIs. Baseline OCD severity (Z = 0.56 [0.21-0.92]), poorer insight (SMD = 1.33 [0.42-1.33]), and presence of comorbid tics (SMD = 0.67 [0.01-1.36]) predicted poor response in continuous outcome analyses.

Conclusions: Baseline severity, insight, and comorbid tics were consistent predictors of poor treatment response.

Introduction: Traditional open-loop SCS is confronted by several major challenges. Variable inconsistent activation of the intended target results in the inconsistency of treatment outcomes and the programming of fixed-output devices below the sensation threshold may not activate dorsal column axons. Closed-loop SCS (CL-SCS) using evoked compound action potential (ECAP) has overcome these limitations with the ability to measure spinal cord activation and accurately administer therapeutic doses despite the dynamic physiologic processes that affect SCS therapy delivery.

Areas covered: The authors present a comprehensive review of CL-SCS treatment and ECAP controlled effects demonstrating long-term benefits and cost-effectiveness compared to fixed output SCS for patients with chronic intractable trunk and limb pain. Several studies have been highlighted by the authors demonstrating superiority in both pain relief and universal treatment responses of ECAP- controlled CL-SCS in comparison to fixed-output open-loop SCS.

Expert opinion: ECAP dose-controlled CL-SCS delivers promising clinical benefits by providing precise, objective control of SCS dosing, aligning with outcomes observed in both RCT and real-world settings. The incorporation of neural metrics into the programming process offers a transparent and reproducible framework for optimizing therapy, enhancing pain relief, and improving universal patient outcomes.

Introduction: In spinal muscular atrophy (SMA), irreversible loss of spinal motor neurons and progressive skeletal muscle atrophy cause continuous weakness and loss of motor function. Treatments that increase levels of survival motor neuron (SMN) protein in motor neurons have greatly improved prognoses for patients, but significant unmet needs remain. Myostatin is a protein secreted by skeletal muscle that acts as a negative regulator of muscle growth. Inhibition of the myostatin signaling pathway may improve motor function in SMA and other neuromuscular diseases.

Areas covered: This article reviews the role of muscle in SMA and the potential for treatments that inhibit the myostatin signaling pathway in neuromuscular diseases. Preclinical and clinical trial data are discussed for these muscle-targeted treatments in development for SMA.

Expert opinion: SMN-targeted disease-modifying treatments focus on motor neuron survival rather than muscle. Treated individuals nonetheless experience a range of persistent muscle weakness. Treatments that inhibit myostatin signaling represent a potential complementary pathway for direct muscle enhancement. In the evolving SMA treatment landscape, understanding how muscle-targeted treatment can be incorporated into clinical practice will facilitate individualized treatment decisions and identify outcomes that best encapsulate maintenance or improvement of motor function across the phenotypic spectrum of SMA.

Introduction: The ketogenic diet as a potential treatment for Alzheimer's disease (AD) has been investigated in several controlled trials. This topic is significant because of the limited nature of current interventions for AD, and the increasing recognition that lifestyle interventions may be important for reducing the risk of AD. The ketogenic diet is one of the few lifestyle interventions that has the potential to be beneficial after diagnosis.

Areas covered: In this narrative review, the authors discuss the biological plausibility of how a ketogenic diet may improve amyloid burden and reduce neuroinflammation by providing an alternative energy source. They review relevant meta-analyses, systematic reviews, and controlled trials to investigate this diet in people diagnosed with AD. To this end, the authors used PubMed to search for appropriate systematic reviews and human trials, and closely examined the bibliographies of these papers to find trials potentially missed in their initial search.

Expert opinion: More research is needed before a ketogenic diet could be broadly recommended in patients diagnosed with AD. However, to the extent a treatment effect has been demonstrated, it is comparable to some pharmaceutical interventions in AD. Challenges that remain include demonstrating improvement in quality of life, improving adherence, and standardizing ketogenic therapies.

Introduction: Anxiety affects approximately 30-40% of adults with autism spectrum disorder (ASD), yet its diagnosis and treatment remain underrepresented in the literature. Autism is a lifelong condition and addressing it across lifespan while considering its developmental stage is essential. Tailored clinical approaches are needed to accommodate communication, cognitive, and sensory differences.

Areas covered: This expert review examines the clinical assessment and evidence-based pharmacological treatment for adults with anxiety disorders.

Expert opinion: Clinicians should redesign workflows to allow developmentally appropriate interviews. Self-reported validated tools, such as HADS-A (Hospital Anxiety and Depression Scale - Anxiety) and Anxiety Scale for Autism-Adults (ASA-A), and adapted versions of Generalized Anxiety Disorder 7-item scale (GAD-7) and Patient Health Questionnaire 9-item scale (PHQ-9) improve diagnostic accuracy, except when caregiver input is necessary. Pharmacological treatments show mixed results: fluvoxamine and clomipramine have shown promise, while citalopram, propranolol, and intranasal oxytocin yielded limited efficacy. Effective treatment of anxiety can improve quality of life, reduce functional impairment, and enhance health outcomes. Equity in care critical to improving access for this underserved population and requires comprehensive education in neurodevelopmental disorders for researchers and clinicians. Further research and innovation are needed to validate tools and optimize treatment strategies for this often-excluded population.

Introduction: Autoimmune optic neuritis (ON) is a heterogeneous spectrum that includes multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), myelin oligodendrocytes glycoprotein antibody-associated disease (MOGAD), and other etiologies. Early and accurate attribution at the first attack is clinically decisive as treatment pathways diverge.

Areas covered: This review synthesizes current knowledge on clinical signs and red flags as well as structured neuro-ophthalmic assessment with data on paraclinical tools including imaging, electrophysiology and fluid biomarkers. This issue is based on literature curated from PubMed/MEDLINE search (January 2000-June 2025; emphasis on 2022-2025) complemented by reference screening of key consensus criteria and landmark studies. Diagnostic gray zones are addressed, including seronegative and unclassified ON, along with practical implementation barriers such as protocol variability, assay access, optical coherence tomography (OCT) interoperability, and reimbursement. Artificial Intelligence (AI) applications for imaging data and mutli-parameter integration are outlined.

Expert opinion: Real-world improvements will depend on standardized diagnostic pathways integrating orbital magnetic resonance imaging (MRI), high-quality antibody assays, OCT, and visual evoked potentials (VEP). Fluid biomarkers such as serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP), together with AI-supported analytics, may refine risk estimates, especially in seronegative cases.

Introduction: Paroxysmal Sympathetic Hyperactivity (PSH) is a historically underrecognized yet increasingly acknowledged syndrome following traumatic brain injury (TBI), characterized by episodic surges in sympathetic nervous system activity. Despite increasing awareness, effective therapy remains unavailable due to diagnostic uncertainty and therapeutic heterogeneity.

Areas covered: In this review, the authors synthesize the recent advances and emerging fronts in the treatment of PSH, encompassing mechanistic understanding, drug discovery, non-pharmacological treatment, and trials in progress. They also outline areas of knowledge deficit and offer suggestions for future research.

Expert opinion: There are several ongoing challenges, including variability in diagnostic approaches and inconsistent outcome measures. There is also an absence of unified treatment protocols that limit clinical consistency and hamper research comparability. Improving alignment between acute ICU management and long-term rehabilitation is similarly important. Moving forward, precision medicine, predictive biomarker development, and individualized treatment modeling offer significant promise. There is optimism that identifying at-risk populations or individuals earlier could enable timely treatment and support the development of more targeted, mechanism-based management strategies that combine both pharmacologic and non-pharmacologic interventions.