Expert Review of Neurotherapeutics最新文献

Introduction: Persistent post-concussion syndrome (PCS) following mild traumatic brain injury (mTBI) represents a growing global health challenge that significantly impacts patients' quality of life. Despite advances in acute concussion management, there remains a critical need for effective, evidence-based treatments for chronic PCS, as current interventions show limited success in addressing both symptoms and underlying pathophysiology.

Areas covered: In this review, the authors examine recent advances in PCS pathophysiology, diagnostic approaches, and therapeutic interventions. The authors evaluate epidemiological trends, advanced neuroimaging findings, validated biomarkers, and emerging treatment modalities such as hyperbaric oxygen therapy, neuromodulation techniques, and biomarker-guided therapeutic approaches.

Expert opinion: Integration of recent evidence suggests a paradigm shift toward personalized, multimodal treatment approaches for PCS, combining targeted physiological interventions with symptom-specific therapies. Future management strategies should focus on early identification of at-risk patients and implementation of evidence-based treatment protocols that address both neurobiological and psychological aspects of recovery.

Introduction: Multiple sclerosis (MS) is a complex disorder driven by both inflammatory and neurodegenerative processes. While disease-modifying therapies (DMTs) have significantly improved prognosis, robust treatment switching criteria remain essential to balance efficacy and safety over the disease course.

Areas covered: This review examines historical and current criteria for escalating DMTs from moderate- to high-efficacy therapies (HET). The authors summarize emerging clinical, imaging, and biological markers that inform decision-making and explore strategies for de-escalation, including DMT discontinuation and innovative approaches such as exit and bridge therapies.

Expert opinion: Recent advances in MS management emphasize earlier initiation of HET and more stringent switching criteria. Although innovative monitoring tools - including clinical evaluations, imaging, biological markers, and patient-reported outcomes (PROs) - enhance disease assessment, they require further validation, standardization, and broader accessibility. Similarly, de-escalation criteria need additional research to optimize patient selection.

Introduction: Parkinson's disease (PD) is a common neurodegenerative disease leading to motor and non-motor disabilities. Broadly accessible fluid- or tissue-based biomarkers will complement neuroimaging and may allow earlier identification and more precise tracking.

Areas covered: The authors have reviewed the recent advances from original full-text English-language articles that were indexed in the PubMed database between June 2023 and June 2024. Articles were identified using the PubMed MESH terms 'Parkinson's Disease' AND 'biomarkers' that focused on using a fluid or tissue-based biomarker to distinguish participants with PD from healthy controls or other conditions. The most promising new biomarkers are those measuring α-synuclein from cerebrospinal fluid or skin biopsy. A significant limitation of these studies is their reliance on a clinical diagnosis of PD, mostly without neuropathological confirmation.

Expert opinion: Mounting evidence supports the validity of CSF and skin biopsy-based detection of α-synuclein for the distinction of PD from healthy controls, although not yet from the spectrum of α-synucleinopathies nor from non-α-synuclein forms of parkinsonism. Nonetheless, the potential to detect individuals who will develop PD may revolutionize our ability to test potential preventive interventions before motor symptoms develop. Machine-learning approaches offer promising strategies for efficient identification and validation of novel biomarkers.

Introduction: Traumatic brain injury (TBI) is a leading cause of long-term disability. N-methyl-D-aspartate receptor (NMDAR) signaling constitutes an important target for pharmacological treatment options.

Methods: The authors have systematically reviewed primary clinical literature reporting on FDA-approved NMDAR antagonist treatment in TBI, based on a set of pre-defined eligibility criteria. Risk of bias assessment was performed using Scottish Intercollegiate Guidelines Network (SIGN) recommendations. Patient characteristics, treatment conditions, and outcomes were reported according to PRISMA guidelines.

Results: This review of five clinical literature databases identified 32 eligible studies. Of 1,827 included patients, the majority (74.8%) experienced severe TBI (weighted mean baseline GCS 6.35). Amantadine (24 studies) variably influenced functional recovery and was linked to adverse effects. Ketamine (five studies) variably lowered intracranial pressure and suppressed spreading depolarization. Memantine and dextromethorphan (2 and 1 studies, respectively) showed favorable safety profiles, though data were limited. Across controlled studies, there was a 0.46 (95% CI: 0.16-0.76) weighted mean difference between control and intervention, favoring NMDAR antagonist treatment.

Conclusions: Future trials should incorporate mechanism-driven biomarkers and must expand research on safe, well-tolerated drugs to improve efficacy and mitigate adverse effects.PROSPERO registration number: CRD42024539051.

Introduction: Long COVID is a condition characterized by persistent unexplained symptoms following COVID-19 infection. These symptoms are not related to another disease or organ damage and are similar to those in fibromyalgia and myslgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Areas covered: The similar clinical and pathophysiological features and management of long COVID, fibromyalgia and ME/CFS are explored from the unifying framework of central sensitivity syndromes. The article is based on a literature search utilizing PubMed for content published between 2021 and 1 May 2025, using search terms: long COVID, long COVID syndrome, post-COVID-19, post-acute SARS-CoV-2, fibromyalgia, ME/CFS, post-exertional malaise and central sensitization.

Expert opinion: Once long COVID is redefined to exclude patients with well-defined organ disease, it fits best as a model of central sensitization. Long COVID is a single syndrome, rather than many distinct diseases. Optimal management of long COVID and similar central sensitivity syndromes should include personalized care with a primary care led-multidisciplinary team.

Introduction: Familial Dysautonomia (FD) is a rare autosomal recessive genetic disease caused by a single point mutation in the ELP1 gene, leading to a deficiency in the Elongator Protein 1. Management has traditionally focused on symptomatic supportive care and prevention of complications. However, promising disease-modifying treatments are now being developed to correct the underlying splicing defect in ELP1.

Areas covered: The authors searched PubMed, GoogleScholar, and clinicaltrials.gov for all types of studies regarding the genetic basis of FD and recent advances in the development of disease-modifying therapies, including publications available through November 2025.

Expert opinion: Experimental evidence indicates that boosting ELP1 protein levels could halt disease progression. Several small molecules and genetic therapies have shown the ability to enhance wild-type ELP1 mRNA and protein expression in animal models. An ongoing N-of-1 clinical trial is evaluating the intrathecal administration of an antisense oligonucleotide (ASO) designed to correct the splicing defect in an individual with FD. Combining small molecules, such as optimized potent oral kinetin derivatives, with intrathecal antisense oligonucleotides (ASOs) and intravitreal gene therapy using viral vectors presents a synergistic therapeutic approach to elevate ELP1 levels. Assessing the efficacy and safety of these targeted strategies will require innovative, well-designed clinical trials.

Introduction: The prevention and treatment of super-refractory status epilepticus (SRSE) remains difficult. Rapid seizure termination and effective management of fatal complications are the keys to improving prognosis.

Areas covered: This review is based on the current literature related to SRSE published in the PubMed database from 2000-March 2025 using the keywords 'SRSE' and 'drug treatment.' The purpose of this article is to shed new light and perspective on the treatment of SRSE.

Expert opinion: SRSE treatment should first target the primary disease that causes SRSE. As the primary disease improves, the frequency of attacks gradually decreases. However, persistent epileptic seizures can cause brain damage and functional disorders, thereby altering the evolution of the primary disease. Therefore, the quick termination of epileptic seizures in patients and the proper management of fatal complications are important measures that can improve patient prognosis. Ketamine, a KD and combination therapy are the most common treatments. Although no consensus has been established, these treatments are generally successful. Neuromodulation, new antiepileptic drugs and surgery are also promising therapeutic areas. However, most reports include individual cases or case series, and thus these drugs and methods should be used with caution.

Introduction: Pediatric-onset multiple sclerosis (POMS) differs from adult MS in its clinical characteristics and disease course. POMS exhibits a heightened inflammatory activity with higher relapse rates and lesion load, alongside less early physical disability but more pronounced cognitive impairment and impaired brain growth.

Areas covered: This review examines treatment strategy in POMS based on safety and efficacy data from observational studies and randomized controlled trials. This article is based on a literature search conducted using MEDLINE and Google Scholar for the period of 2000 to 2024.

Expert opinion: High-efficacy therapies, including fingolimod, natalizumab, and anti-CD20 therapies, have demonstrated superior disease control and disability prevention. Early initiation of HET is increasingly recommended to optimize outcomes and preserve quality of life.Low/moderate-efficacy therapies, such as interferons, glatiramer acetate, teriflunomide, dimethyl fumarate should be reserved for patients with mild disease. While long-term safety data, personalized prognostic markers and de-escalation strategies are still needed, high-efficacy therapies provide a promising standard of care, especially given enhanced neuroinflammatory activity in POMS. Future research should prioritize strategies to balance disease control with adverse effects (AEs), accounting for aging and individual disease trajectories, to improve long-term quality of life in POMS patients.

Introduction: Fragile X Syndrome (FXS) is the most frequent inherited form of intellectual disability and a common cause of autism spectrum disorders and other neurodevelopmental conditions. It is commonly associated with hyperarousal, anxiety, and behavioral difficulties such as agitation, self-injurious behavior, and aggression.

Areas covered: This narrative review covers the physical, cognitive, and behavioral phenotype associated with FXS and the evidence for pharmacological interventions for behavioral difficulties, including those prescribed on the basis of symptoms and those aimed at the pathophysiological mechanisms of FXS ('targeted' interventions). Consideration is then given to the evidence for novel targeted treatments currently in later stages of clinical development.

Expert opinion: The first-line management of behavioral difficulties are non-pharmacological interventions, and there are only a few studies in FXS to guide pharmacological approaches. Identification and management of anxiety and ADHD, which contribute to behavioral difficulties, are important steps before considering antipsychotic treatment for agitation, aggression, or self-injurious behavior. The evidence for repurposed targeted treatments remains based on small RCTs or open-label studies; therapeutic trials of these interventions therefore need close monitoring. Multiple novel medications are in clinical development; genetic therapies remain preclinical but are likely to be important in the coming years.