Expert Review of Neurotherapeutics最新文献

Introduction: Delayed cerebral ischemia (DCI), often linked to cerebral vasospasm, is a major cause of death and disability after aneurysmal subarachnoid hemorrhage (aSAH). Nimodipine remains the only Food and Drug Administration (FDA)-approved drug for DCI prevention.

Areas covered: The authors review clazosentan, a selective endothelin-A receptor antagonist approved in Japan and South Korea. This drug profile is based on searches utilizing PubMed/MEDLINE, Embase, Cochrane Library, Web of Science, and Google Scholar from database inception through to March 2025 using terms including 'clazosentan,' 'aneurysmal subarachnoid hemorrhage,' 'cerebral vasospasm,' 'delayed cerebral ischemia,' and trial identifiers (CONSCIOUS, REACT, REVERSE). The authors included Phase I-IV clinical studies, PK/PD studies, and meta-analyses; preclinical reports and non-peer-reviewed abstracts were excluded, prioritizing randomized controlled trials and large syntheses.

Expert opinion: Clazosentan consistently reduces angiographic vasospasm and vasospasm-related complications, yet durable improvements in functional outcomes have been inconsistent across international trials. Safety concerns like pulmonary complications, anemia, and fluid retention require vigilant monitoring, particularly in elderly or hepatically impaired patients. Recent Japanese Phase III trials and real-world cohorts suggest benefit in selected populations and practice settings, supporting clazosentan as an adjunct to standard care rather than a replacement. Further work should refine dosing, patient selection, and combination strategies that target microvascular dysfunction and neuroinflammation beyond large-vessel spasm.

Introduction: Mobile health (mHealth) technologies have the potential to revolutionize the management of Parkinson's disease (PD) by providing objective data on symptom severity, fluctuations, and response to treatment.

Areas covered: Herein, the author reviews the latest articles including randomized clinical trials and meta-analyses, on the current and emerging mobile health technologies used in the management of PD. The mobile health technologies discussed include wearable devices, smartwatches and smartphones.

Expert opinion: Digital health technologies have added value in the monitoring and management of PD. Wearable sensors, smartphone applications, virtual reality environments, and tablet-based cognitive tools continuously collect objective data on motor symptoms, including tremors, gait, and bradykinesia, taken in a patient's daily environment. These technologies provide data for remote therapeutic adjustments and rehabilitative planning, improving patient convenience and potentially enhancing their quality of life. However, limitations do exist including: the lack of international guidelines, the cost of wearable devices and data analysis services, and device heterogeneity. Future studies are necessitated to better refine algorithmic thresholds and validate digital tools, while also providing patients with clear transparency and ensuring complete data security, if there is to be widespread uptake of this potentially valuable technology for delivering more personalized treatment plans for people with PD.

Background: The post-stroke spasticity (PSS) Referral Tool was developed to assist health care professionals in the early identification of patient referral needs. An inter-rater reliability (IRR) study using videos of patients with different stages of or without predictors of PSS was performed to validate its utility in clinical practice.

Research design and methods: This prospective study had 3 parts: patient video production (Part A); expert panel classification of patient videos into PSS Referral Tool categories (Part B; Urgent Referral [UR; red], Routine Referral [RR; yellow], Periodic Monitoring [PM; green]), and an IRR analysis from global clinician raters (Part C). IRR was estimated using the intra-class correlation coefficient (ICC) with a 2-way random effect, absolute agreement, single-measurement model ( < 0.50 [poor]; 0.50-0.75 [moderate]; 0.76-0.90 [good]; > 0.90 [excellent]).

Results: In total, 50 raters participated and 70% had no prior experience using the PSS Referral Tool. IRR (ICC [95% CI]) was moderate (0.68 [0.53, 0.84]) and most video ratings were correct (UR/RR: 69.2% [173/250]; PM: 88.0% [220/250]). Sensitivity was highest in raters with no or moderate experience (93.3% [14/15]).

Conclusions: Irrespective of previous experience and geographic region of practice, the PSS Referral Tool accurately identified patients at risk for PSS.

Introduction: Alzheimer's disease (AD) and epilepsy frequently co-occur and are risk factors for each other's onset. In patients with AD-comorbid epilepsy, seizure control with appropriate anti-seizure medications (ASMs) is crucial, yet no established treatment guidelines exist. Recent studies indicate that α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPARs) are involved in the pathogenesis of both diseases. Perampanel, an AMPAR antagonist, has been approved as an ASM.

Areas covered: This review explains the relationship between AD and epilepsy and discusses the involvement of AMPARs. Furthermore, it focuses on and presents opinions regarding the role of AMPAR inhibitors in the treatment of AD-comorbid epilepsy. The authors searched for clinical studies that were published and identifiable in PubMed and Scopus (Jan 2015-Dec 2024) including the terms 'Alzheimer's disease' or 'dementia' with 'epilepsy' or 'seizure'.

Expert opinion: Considering the hypothesis that AD and epilepsy are linked, creating a cycle that progresses both diseases via AMPARs, AMPAR inhibition may have beneficial effects in treatment of epilepsy in AD. Although evidence is limited, studies of perampanel have demonstrated symptomatic improvement in patients with AD-comorbid epilepsy. Perampanel may be particularly useful for specific subgroups of patients with AD-comorbid epilepsy, such as those with myoclonus, sleep disturbances, or poor medication adherence.

Introduction: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and gait impairments. Levodopa remains the cornerstone of pharmacological treatment. This review examined the acute effects of oral levodopa on motor symptoms and gait parameters in people with PD.

Methods: PubMed and Embase were searched up to February 17^th 2025. Included studies presented within-subject comparisons between ON- and OFF-medication states, assessing outcomes such as UPDRS motor scores, clinical walking tests, and spatiotemporal gait metrics. Study quality was assessed using the NIH quality assessment tool for before-after studies without control groups. Standardized mean changes (SMC) were calculated to quantify treatment effects. Studies with incomplete data were qualitatively reviewed.

Results: Thirty-nine papers (38 studies; 1425 participants) were included. Levodopa significantly improved the (MDS)-UPDRS motor score (SMC =  -1.49 [-1.77, -1.22]), corresponding to a mean decrease of -14.0 points [-16.7, -11.48]. Stride/step length (0.76 [0.44, 1.08]), gait velocity (0.75 [0.48, 1.01]), and clinical walking tests (-0.50 [-0.78, -0.21]) also improved. Effects on other gait characteristics (i.e., step width, stance/swing/step time, gait cycle duration, and swing/stance phase) were limited.

Conclusions: Oral levodopa induces substantial acute improvements in motor symptoms and key gait parameters but has limited effects on other gait characteristics, emphasizing the need for complementary and individualized interventions.

Introduction: Atypical meningiomas (WHO Grade 2) comprise approximately 18% of all meningiomas and may recur, despite surgical resection. Current evidence, derived from prospective cohort studies and retrospective series, supports the use of radiotherapy in achieving local control in atypical meningiomas. Given the lack of level 1 data, the role of RT in the management of recurrent disease in radiotherapy-naïve or previously irradiated patients remains a subject of ongoing debate, and optimal strategies are yet to be established.

Areas covered: This narrative review examines recent developments in radiotherapy techniques, including dose escalation and particle therapy, alongside advances in imaging and molecular profiling relevant to meningioma management. The authors summarize the existing evidence and provide an updated perspective on the evolving role and value of radiotherapy in treating recurrent atypical meningiomas. This article also proposes a new treatment algorithm. This review is based on a literature search using PubMed to identify relevant studies on recurrent atypical meningioma (WHO grade 2) up to August 2025. Key references from recent guidelines and high-impact studies were also included.

Expert opinion: The authors believe that treatment plans for recurrent atypical meningioma should consider prior radiotherapy exposure. The integration of PET-guided radiotherapy planning and molecular-based risk stratification will allow for personalized treatment plans, setting a framework for its future clinical management.