Expert Review of Neurotherapeutics最新文献

Introduction: Blepharospasm is a type of dystonia associated with overactivity of the orbicularis oculi and nearby muscles causing significant disability. Available treatments are only symptomatic, and many patients experience disability related to incomplete symptom relief.

Areas covered: The authors provide a review the phenomenology of blepharospasm and its usual treatments. The evidence for botulinum toxin, oral pharmaceuticals and surgical treatments are summarized. Despite considerable phenotypic heterogeneity, the literature indicates a standardized approach to treatment is often pursued. PubMed was used as the primary source database for the literature reviewed relating to the treatment of blepharospasm published between April 1985 and May 2025.

Expert opinion: Although a standardized approach to treatment is common, a customized approach with attention to the particular combination of motor and non-motor symptoms occurring in individual patients improves therapeutic outcomes. The anatomical rationale and experience supporting a more personalized treatment strategy is emphasized. Also summarized are specific topics and strategies that are the subject of ongoing research to optimize the care of blepharospasm in the future.

Introduction: Arterial ischemic stroke (AIS) represents a significant cause of neurological morbidity and mortality in the pediatric population, with reported mortality rates ranging from 2% to 9%. The growing evidence supporting the efficacy and safety of reperfusion therapies in pediatric AIS underscores the critical importance of timely and accurate diagnosis. There are many barriers to achieving this, including a lack of clinical recognition and diagnostic imaging delays.

Areas covered: This narrative review highlights key advances in reperfusion therapies, acute neuroimaging, advanced imaging, and the development of stroke pathways. It explores the growing understanding of the etiology and genetics of childhood AIS. A comprehensive literature search was performed using PubMed, Medline, and EMBASE for relevant studies and reports, as well as reviewing published guidelines available through March 2025.

Expert opinion: Pediatric AIS remains challenging due to its infrequent occurrence, diagnostic complexity, and system-level barriers. Advances in imaging and development of streamlined pediatric stroke pathways are shortening the time to diagnosis, but future advances will rely on integration within established adult systems of care, the use of telemedicine and the development of pediatric perfusion imaging expertise. Evolving knowledge of pediatric neurovascular genetics and secondary imaging modalities will lead to tailored management of conditions with stroke risk.

Introduction: High-grade gliomas remain difficult to treat due to their infiltrative growth, therapeutic resistance, and the restrictive blood-brain barrier (BBB). Focused ultrasound (FUS) offers a noninvasive method to transiently disrupt the BBB, enhancing the delivery of therapeutics to the tumor site.

Areas covered: Herein, the authors discuss the emerging role of FUS in glioma treatment including enhanced drug delivery, real-time monitoring techniques, and biomarker-driven patient selection. They also explore the impact of combined FUS with immunotherapy, gene therapy, exosome-based drug delivery, sonobiopsy, and radiotherapy (RT) sensitization. The authors have based their article on literature published between January 2010 and October 2024 from PubMed, Web of Science, and Google Scholar. By tailoring FUS parameters to individual tumor characteristics and patient responses, these strategies aim to overcome glioma heterogeneity and treatment resistance, further advancing personalized therapeutic approaches.

Expert opinion: The integration of FUS into neuro-oncology represents a paradigm shift, requiring interdisciplinary collaboration to maximize its potential as a cornerstone of precision medicine in glioma treatment. Future advancements in FUS will likely focus on refining treatment protocols, optimizing real-time targeting, and integrating artificial intelligence (AI)-driven predictive models to personalize therapy.

Introduction: Cerebral amyloid angiopathy (CAA) is a leading cause of intracranial hemorrhage and cognitive decline, resulting from amyloid-β accumulation in the walls of small cortical and leptomeningeal arterioles. While models of pathogenesis exist, the mechanisms leading to the diverse clinical manifestations of CAA remain largely unknown. There are no proven treatments, but a few clinical trials are ongoing. Meanwhile, emerging anti-amyloid-β therapies and managing patients with comorbidities including atrial fibrillation complicate clinical-practice in peopel with CAA.

Areas covered: Herein, the authors provide their perspectives on CAA from initial amyloid-β deposition to clinical disease manifestations. They also discuss the emergence of iatrogenic CAA and the potential role of inflammation across CAA, questioning the concept of a single entity. Finally, the authors examine management challenges, future research horizons, and treatment directions.

Expert opinion: Recent insights challenge the traditional view of a linearly progressive disease, suggesting a dynamic natural history with periods of high activity and remission. Inflammation is a topic of active investigation, with potential therapeutic relevance. Challenges remain, including the need for improved neuroimaging and fluid biomarkers for noninvasive early diagnosis. Iatrogenic CAA is a recently described amyloid-β prion disease in younger people, with known Aβ innoculation and exposure times, providing a potential 'pure' model of CAA. Research into limiting Aβ production, improving perivascular clearance, or modifying vascular remodeling and inflammation may guide novel therapeutics.

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.