Expert Review of Neurotherapeutics最新文献

Introduction: Alongside core diagnostic symptoms, Alzheimer's disease (AD) and Parkinson's disease (PD) involve early and pervasive speech-language impairments (SLI), often appearing in preclinical stages and capturing disease severity. However, speech language outcome measures are under-represented in clinical trials, missing out on critical clinical outcome assessments (COAs).

Areas covered: The purpose of this review is to survey the findings from classical (analogical) and novel (digital) speech-language measures as pathways toward more precise diagnosis and response to treatment indices in interventional clinical trials. This narrative review covers two main areas; first, it examines the strengths and limitations of SL measures in traditional cognitive testing scales to identify adequate COAs for AD and PD. Second, it overviews findings on classical and digital COAs that hold great promise despite their widespread absence in clinical trials.

Expert opinion: Incorporating strategic SL COAs in clinical trials may identify early, severity-sensitive deficits and enhance the clinical insights thus obtained. The modification of clinical trial designs will nevertheless be required to increase sensitivity to identify meaningful clinical outcomes.

Introduction: Fibromyalgia is a chronic pain syndrome characterized by widespread nociplastic pain, fatigue, sleep disturbances, and mood symptoms. Conventional treatments often yield limited benefits, prompting interest in noninvasive brain stimulation techniques such as transcranial direct current stimulation (tDCS).

Areas covered: This review synthesizes evidence from 31 randomized controlled trials (RCTs) evaluating the efficacy, safety, and tolerability of tDCS in fibromyalgia. A systematic search of Embase and Medline were conducted without date or language restrictions. Most studies assessed anodal tDCS targeting the primary motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC), with outcomes spanning pain, global symptom burden, psychological symptoms, fatigue, and sleep quality. Ten of 14 sham-controlled trials reported significant pain reductions with M1 stimulation. Seven trials showed improvements in overall symptom severity (FIQ/FIQR), though most did not meet the minimal clinically important difference. Outcomes for fatigue, sleep, and mood were less consistent and often underreported.

Expert opinion: While tDCS appears safe and effective for fibromyalgia-related pain, variability in protocols and limited reporting of non-pain outcomes hinder broader conclusions. As an adjunctive therapy, its role may be enhanced through protocol standardization, longer-term follow-up, and combination strategies such as pairing with repetitive transcranial magnetic stimulation (rTMS) to address the full spectrum of fibromyalgia symptoms.

Introduction: Over recent decades, research has identified both overlapping and distinct characteristics, risk factors, and genetic as well as neurobiological correlates associated with Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD). This expanding body of evidence is increasingly informing the clinical management of individuals with comorbid ADHD and ASD.

Areas covered: Based on a targeted PubMed search conducted up to March 24,2025,24.03.25, prioritizing meta-analyses or umbrella reviews over primary studies (whenever relevant), with terms encompassing autism, assessment, and treatment, this review addresses: 1) Shared and distinct phenotypic characteristics, neuropsychological features, and genetic and neuroimaging correlates of ADHD and ASD; 2) The assessment of individuals presenting with both ASD and ADHD symptoms; 3) Pharmacological and non-pharmacological strategies for the management for individuals with comorbid ASD and ADHD.

Expert opinion: The comorbidity of ADHD and ASD should not be overlooked. Nevertheless, before diagnosing comorbid ASD and ADHD, clinicians should perform a thorough differential diagnosis, ensuring that ADHD symptoms are not better explained by ASD. Regarding treatment, further research is warranted to develop personalized approaches, support long-term management strategies, and evaluate real-world outcomes such as quality of life, which are often underrepresented in clinical trials.

Introduction: Medication-overuse headache (MOH) is a secondary headache disorder arising from the excessive use of acute headache medications, most commonly triptans and nonsteroidal anti-inflammatory drugs (NSAIDs). Traditional management relies on education strategies and drug withdrawal followed by preventive therapy, but relapse rates remain high and detoxification is not always feasible.

Areas covered: This review summarizes current evidence on anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies in migraine patients with medication overuse or MOH. A structured literature search was conducted in PubMed and Scopus for studies published up to August 2025. Erenumab, fremanezumab, galcanezumab and eptinezumab consistently reduced headache frequency, acute medication intake and disability, even when initiated without prior withdrawal of overused drugs. Rates of remission from MOH to non-overuse status were high, and safety profiles were comparable to those observed in general migraine populations.

Expert opinion: Anti-CGRP antibodies offer a targeted strategy capable of interrupting the cycle of overuse and sensitization underlying MOH. Early initiation of anti-CGRP therapy during ongoing overuse appears effective and well tolerated, but long-term outcomes are likely improved when treatment is accompanied by patient education and, in selected cases, structured withdrawal.

Introduction: Robot-assisted gait training (RAGT) has gained prominence in stroke rehabilitation, promoted as a technologically advanced intervention to improve walking outcomes. However, evidence from clinical trials and systematic reviews paints a more equivocal picture. Despite its widespread adoption, questions persist regarding its true clinical utility and whether it offers meaningful benefits beyond conventional physiotherapy.

Areas covered: This perspective evaluates the evidence base for RAGT by critically reviewing recent systematic reviews and randomized controlled trials, with particular attention to study designs, comparator interventions, and reported outcomes. It highlights the overreliance on surrogate outcomes and underlines the need to focus on meaningful functional endpoints like walking independence and community mobility. Studies that directly compare RAGT with task-specific overground gait training (TOGT) are emphasized, as these provide the most relevant insights into RAGT's additive value.

Expert opinion: Without evidence of clear additive value, the continued emphasis on RAGT may reflect technological enthusiasm more than therapeutic necessity. The field must reconsider its priorities, redirecting research efforts toward optimizing scalable, high-intensity TOGT that aligns more closely with real-world functional recovery. Future research should prioritize direct comparisons between RAGT and optimized TOGT, with a stronger focus on outcomes that matter to patients.

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: Medulloblastoma is the predominant malignant neuroepithelial tumor in the central nervous system among children and is recognized as one of the most aggressive tumor types. Despite advances in multimodal therapy, prognosis for certain subgroups remains poor, and survivors often face severe long-term sequelae. Artificial intelligence (AI), a field focused on enabling computers to replicate human-like intelligent behavior, is increasingly being applied to the management of challenging diseases.

Areas covered: In this review, the authors provide a comprehensive overview of AI applications across the entire clinical spectrum of medulloblastoma. Using articles retrieved through literature searches from PubMed and Google Scholar, through to early 2025, the authors cover AI's roles in radiological segmentation and diagnosis, noninvasive molecular subtyping, pathological analysis, tumor microenvironment characterization and prognosis prediction. The review critically appraises the current evidence level for these technologies, from proof-of-concept to clinical validation.

Expert opinion: AI holds immense promise for personalizing medulloblastoma care, but its clinical integration faces significant hurdles. Key challenges include the need for large, diverse datasets, robust multi-center validation, improved model interpretability, and addressing pediatric-specific ethical concerns. Future success will depend on interdisciplinary collaboration to translate these powerful tools into safe, effective, and equitable clinical practice, ultimately improving outcomes for children worldwide.