Expert Review of Neurotherapeutics最新文献

Introduction: Optimal sleep duration is increasingly recognized as an important determinant of overall health, including cognitive functioning. Studies often report a U- or J-shaped relationship between sleep duration and incident dementia or cognitive deterioration, whereas long sleep, the extremes of sleep duration, and the transition to long sleep were particularly detrimental. In preclinical studies, partial or complete sleep deprivation produced inflammation, oxidative stress, as well as increased tau hyperphosphorylation and amyloid-β burden. In humans, although the findings are less pronounced, they still highlight that transitioning to an excessive sleep duration is associated with neurodegeneration. Moreover, the association between sleep duration and dementia is complex and modified by genetic, psychosocial and lifestyle factors, along with psychiatric and somatic comorbidities.

Areas covered: The purpose of this perspective is to summarize the current knowledge on the association between sleep duration and dementia. It is based on a literature search for meta-analyses of prospective studies with sleep duration as an exposure and dementia as an outcome.

Expert opinion: Sleep duration is a modifiable risk factor for dementia while long sleep may be an early sign of neurodegeneration. Therefore, self-reported sleep duration is an easy-to-use tool for detecting individuals who may be at risk for cognitive deterioration.

Introduction: MS is a disease continuum in which maladaptive inflammation and neurodegeneration co-occur from onset and evolve over time. Recent progress in the understating of MS pathobiology creates new perspectives for novel neuroprotective therapeutic strategies.

Areas covered: The authors briefly review the mechanisms underlying inflammation and neurodegeneration in MS and discuss the current and emerging strategies to promote neuroprotection in MS. Data were derived in large part from extensive review of the published literature available on PubMed (up to 5th of March 2025).

Expert opinion: Strategies for neuroprotection should be ideally implemented early in the course of MS. They should consider the interplay between neuroinflammation, demyelination and neurodegeneration, the maladaptive changes in the CNS innate immunity resident cells, axonal mitochondrial dysfunction (axonal response of mitochondria to demyelination, ARMD), and remyelination. There is a need for adequate biomarkers that can help to monitor outcomes of target engagement. Comorbidities and aging can worsen neurodegeneration and impair neuroprotective/regenerative processes. Candidate drugs from preclinical and early clinical studies should be tested in multi-arm multistage adaptive trials.

Introduction: Despite decades of research, effective disease-modifying treatments for Amyotrophic Lateral Sclerosis (ALS) remain scarce. The emergence of regenerative medicine presents a new frontier for ALS treatment.

Areas covered: This review is based on a comprehensive literature search using PubMed, Scopus and clinical trials databases on the recent therapeutic advancements in ALS, giving focus to regenerative medicine. The article includes coverage of stem cell-based therapies, including mesenchymal, neural and induced pluripotent stem cells; all of which may offer potential neuroprotective and immunomodulatory effects. Gene therapy, particularly antisense oligonucleotides targeting ALS-related mutations, has gained traction, with tofersen becoming the first FDA-approved genetic therapy for ALS. The article also covers emerging approaches such as extracellular vesicles, immune-modulating therapies, and bioengineering techniques, including CRISPR-based gene editing and cellular reprogramming, that hold promise for altering disease progression.

Expert opinion: While regenerative medicine provides hope for ALS patients, significant challenges remain. Biomarkers will play a crucial role in guiding personalized treatment strategies, ensuring targeted interventions. Future research should prioritize optimizing combinatory approaches, integrating different therapy strategies to maximize patient outcomes. Although regenerative medicine is still in its early clinical stages, its integration into ALS treatment paradigms could redefine disease management and alter its natural course.

Introduction: Diagnosing autism spectrum disorder (ASD) in adults is challenging due to its heterogeneity and symptom overlap with other conditions. Making an accurate diagnosis can be difficult and overwhelming but is vital for proper accommodations and interventions while avoiding unproductive or harmful treatments.

Areas covered: The authors have based their review on a comprehensive literature search using PubMed, PsycINFO, and Google Scholar to identify relevant recommendations, diagnostic tools, and common differential diagnoses for adults with ASD. A clinical framework is provided based on the DSM-5 criteria, starting with an evaluation of childhood symptom onset and persistent manifestations of the core criteria - social and communication impairment, along with restricted, repetitive behaviors. Conditions with overlapping presentations, including personality disorders, anxiety, depression, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, and schizophrenia, are discussed, as well as challenges in differentiating these from ASD.

Expert opinion: Many factors complicate diagnosing ASD in adults - such as skewed public perception or misinformation spread on social media. Existing tools frequently miss subtle or atypical presentations, particularly in underdiagnosed groups like women and older adults. Promising advances in machine learning and artificial intelligence will hopefully improve diagnostic precision in the future. Up-to-date clinician training and large-scale research remain paramount for refining adult ASD diagnosis.

Introduction: Intracerebral hemorrhage (ICH) accounts for 10% of strokes; however, compared with ischemic stroke, progress leading to novel treatments and improved patient outcomes has been lacking. Recently, there have been several promising developments and renewed research interest within the field. Positive results from randomized controlled trials have now been reported in multiple domains of care for patients with ICH. Anticoagulation-associated ICH is increasingly frequent, and clinicians deciding on reversal and timing of re-initiation of oral anticoagulation now have more therapeutic agents available and evidence to guide them. Minimally invasive techniques are also added to the neurosurgical arsenal, leading to improvements in functional outcomes. Acute treatment at presentation is best served by bundled care approaches, which ensure goal-directed management of blood pressure, glucose and temperature.

Areas covered: This narrative review summarizes the recent developments in this area, as well as the current recommendations of key international guidelines. Literature search was carried out using PubMed database with priority given to publications since 2020.

Expert opinion: There is renewed optimism for innovation in ICH. The standard of care for this condition now leads to improvements in mortality and long-term functional ability. Efforts to improve the patient selection and surgical techniques for operative management are ongoing.

Introduction: Alzheimer's disease (AD), the leading cause of dementia, poses a significant burden on patients, caregivers, and healthcare systems worldwide. After two decades of extensive efforts, we are still without significantly effective disease-modifying drugs for AD. Although brain amyloid-β (Aβ) accumulation may predict cognitive decline, several drug candidates, including anti-Aβ monoclonal antibodies, have been developed and tested to reduce Aβ plaque burden effective, but without significant clinical success.

Areas covered: The following review presents and discusses anti-Aβ monoclonal antibody therapeutics used to treat AD. The article considers both current approaches and alternatives. This article is multiple database searches (MEDLINE, EMBASE, Scopus, Ovid and Google Scholar) on all the available literature up to 1 February 2025.

Expert opinion: Randomized clinical trials (RCTs) of anti-Aβ drugs in AD have not fully validated the Aβ cascade hypothesis. Nevertheless, eight anti-Aβ monoclonal antibodies have, thus far, made it to Phase III RCTs. Moving forward, the use of the Apolipoprotein E genotype and tau protein as alternative biomarkers can assist clinicians in providing patients with even more individualized and efficacious anti-Aβ monoclonal antibodies dosing regimens and reduce the risk of serious amyloid-related imaging abnormalities.

Objectives: Parkinson's disease (PD) often presents with neuropsychiatric symptoms that worsen quality of life. The aim of this study was to evaluate the effectiveness of Botulinum neurotoxin-A (BTX-A) in managing neuropsychiatric manifestations in PD patients.

Methods: Neuropsychiatric status was assessed in 185 PD patients using the Cornell Medical Index (CMI). Ninety-four patients exhibiting neuropsychiatric symptoms were randomly assigned to two groups: BTX-A (n=47, local injections) and citalopram (n=47, 10-40 mg/day). Outcomes were compared at baseline and 8 weeks post-treatment.

Results: The authors findings revealed a significant reduction in somatization, tension, anxiety, depression, sensitivity, and overall scores in the BTX-A group at the eight-week follow-up (p < 0.05 for all). Notably, patients in the BTX-A group exhibited similar levels of somatization, depression, anxiety, maladjustment, sensitivity, anger, and overall scores compared to the citalopram group (p > 0.05 for all). Both groups reported comparable percentages of improvement in neuropsychiatric symptoms (75.6% vs. 82.6%, p = 0.57).

Conclusions: This study demonstrates the potential of BTX-A in alleviating tension, anxiety, depression, sensitivity, and other neuropsychiatric symptoms in PD patients. Importantly, BTX-A's efficacy was comparable to that of citalopram, suggesting its potential as a viable therapeutic option for managing neuropsychiatric manifestations in PD.

Introduction: Disorders of consciousness (DoC) are characterized by impaired arousal and/or awareness, ranging from coma to unresponsive wakefulness syndrome, minimally conscious state, and cognitive motor dissociation. Pharmacological treatment options remain limited, complicated by the heterogeneity of etiologies, such as traumatic brain injury, stroke, and infections. The lack of rigorous clinical trials has led to off-label use of treatments, often without clear mechanistic understanding, posing challenges for effective patient care.

Areas covered: In this perspective, the authors report on key studies concerning the effectiveness of pharmacological interventions, including dopaminergic and GABAergic agents, antidepressants, statins, and anticonvulsants, in promoting recovery of consciousness in DoC.

Expert opinion: Robust longitudinal clinical trials are needed, with priority given to early subacute phase intervention. Outcomes should be better defined, considering immediate responses to medication while also increasing the emphasis on long-term quality of life. Unified functional and mechanistic frameworks are needed to guide research and foster collaboration. Furthermore, a shift toward personalized medicine would benefit this heterogeneous population. Moving forward, assessing the efficacy of more unconventional or 'paradoxical' pharmacological options in treatment plans will be essential. The authors also expect an increased use of AI tools to identify factors that best predict treatment responses.