Current Neuropharmacology最新文献

Introduction: Post-stroke tremor and post-stroke thalamic pain (PS-TP) are common and often refractory conditions that significantly impact patients' quality of life. Conventional pharmacotherapy frequently provides inadequate relief, while cannabis has shown potential for managing movement disorders and pain; however, evidence supporting its efficacy remains limited. On the other hand, physiotherapy is well-documented as an effective therapeutic intervention.

Case presentation: This case report aimed to evaluate the combined effects of cannabis oil and physiotherapy on dystonic-tremor and PS-TP in a female subject with a history of thalamic ischemia. The patient was monitored over a 1-year follow-up period with assessments focused on pain intensity, tremor severity, and overall functional improvements. After twelve months of treatment, the patient demonstrated a 60% reduction in pain and a 56.88% reduction in tremor severity, accompanied by enhanced motor function. Furthermore, quality of life improved significantly, with a 27.6% increase in the mental component and a 45.46% increase in the motor component. No serious adverse effects were reported during the treatment period.

Conclusion: This case report highlights the potential benefits of combining cannabis oil with physiotherapy for managing post-stroke dystonic tremor and PS-TP. The sustained efficacy of this treatment combination over a prolonged period could constitute a therapeutic novelty and an important advancement in the management of these conditions. These findings suggest the need for further research with larger cohorts and studies of higher methodological rigor to establish the efficacy and safety of this therapeutic approach.

Background: The mechanisms of neurodegeneration common to many neurodegenerative diseases include oxidative stress, mitochondrial dysfunctions, excitotoxicity, and others. Beyond the broad spectrum of strategies for developing neuroprotective agents that target stagespecific mechanisms in each neurodegenerative disease, considerable attention is also being given to approaches aimed at developing compounds that can effectively modulate general pathogenic mechanisms and enhance the overall resilience of neuronal cells to cell death induction.

Objective: This review discusses some of the results on new multitarget multipharmacophore agents with neuroprotective effects, particularly through their influence on mitochondrial permeability transition and antioxidant properties. We conducted comprehensive online searches on PubMed to gather the latest data on multitarget multipharmacophore agents consisting of pre-defined pharmacophores that have already demonstrated neuroprotective properties.

Results and discussion: To create compounds with a desirable spectrum of biological activity, an approach based on the conjugation of specific structural fragments of pharmacologically active substances into a single molecular entity could be used. Core fragments of compounds that have already demonstrated neuroprotective properties due to mitochondrial and antioxidant mechanisms of action can be used as neuroactive scaffolds.

Conclusion: The combination of several pharmacophores in one molecule may not only result in the mere addition of the useful properties of each component, but may also give rise to new types of biological activity. The examples of the appearance of new properties in such multipharmacophore compounds, not inherent in the reference agents, discussed in our review, may be considered a prospective approach for creating a novel generation of neuroprotective agents.

Introduction: To explore the role of tocilizumab in treating childhood immune-mediated epilepsy and determine the role of interleukin-6 (IL-6) in its pathogenesis.

Methods: We collected and analyzed clinical information of pediatric patients diagnosed with immune- mediated epilepsy and treated with tocilizumab at Xiangya Hospital.

Results: This study included four males with a median age of onset of 4.3 years. They presented with seizures, fever, and neuropsychiatric manifestations. A combination of different anti-seizure medications (ASMs) and first-line immunotherapy could not control seizures. All patients had elevated levels of IL-6 in their serum and/or cerebrospinal fluid at some points. The median time from disease onset to the first dose of tocilizumab was 25 days. Patients 2 and 3 received tocilizumab in the acute phase of the disease, but patients 1 and 4 received this therapy in the subacute phase. At the last follow-up, patients 2 and 3 had no seizures, while patients 1 and 4 still had chronic epilepsy, but with > 50% reduction of seizure frequency. All patients regained normal cognition.

Discussion: IL-6 may play a role in the pathogenesis of immune-mediated epilepsy, and introducing tocilizumab in the acute phase might be effective in preventing the disease from progressing into the chronic phase.

Conclusion: Tocilizumab is effective for the management of immune-mediated epilepsy in children when given early enough.

Introduction: Sleep disorders are prevalent but frequently overlooked in Moyamoya Disease (MMD), with their clinical impact remaining inadequately characterized. This study aimed to determine the prevalence of sleep disorders, assess their effect on functional outcomes, and identify independent predictors in MMD patients.

Methods: This prospective cohort study enrolled 320 consecutive adult MMD patients. Sleep quality, anxiety, depression, and insomnia symptoms were evaluated using the PSQI, SAS, SDS, and AIS, respectively. Two independent reviewers assessed clinical and radiological outcomes. Multivariate logistic regression was employed to identify independent risk factors for sleep disorders.

Results: Of the 320 patients (184 females, mean age 45±11 years), 52.1% with sleep disorders had poor functional outcomes (mRS≥2) at admission, which persisted in 55.1% at 3 months post- EDAS. Multivariate analysis revealed that female gender (OR: 5.37, 95% CI: 2.30-12.56), older age (OR: 1.05, 95% CI: 1.01-1.09), headache (OR: 9.25, 95% CI: 1.96-43.67), alcohol consumption (OR: 3.94, 95% CI: 1.68-9.22), anxiety (OR: 4.18, 95% CI: 1.44-12.16), depression (OR: 21.22, 95% CI: 2.53-177.90), higher admission and postoperative mRS scores, and impaired hemodynamic parameters (TTP, rCBV, rCBF) were independent risk factors. Sleeping pill use was a protective factor (OR: 0.16, 95% CI: 0.06-0.42).

Discussion and conclusion: Sleep disorders are common and adversely impact functional recovery in MMD, yet remain underrecognized. The identified multivariable risk profile underscores the necessity of integrating routine sleep screening and comprehensive management into standard MMD care to improve patient prognosis.

Background: Hyperprolactinemia (HPRL) can lead to various health complications. Among patients with schizophrenia, it may be linked to antipsychotic medications and other contributing factors. Sex-based differences in HPRL have been observed, and its association with breast cancer in this population remains unclear.

Objective: To investigate overall and sex-specific risk factors for HPRL in patients with schizophrenia and to examine the incidence of breast cancer in this population.

Methods: A retrospective cohort study was conducted among inpatients with schizophrenia who underwent prolactin monitoring in a Chinese hospital. Participants were categorized into HPRL and non-HPRL groups, and binary logistic regression was performed to identify factors associated with HPRL.

Results: Among 1,425 patients analyzed, the overall incidence of HPRL was 63.37%, with higher rates in females (67.99%) compared to males (57.31%). HPRL was positively associated with thyroid- stimulating hormone levels, repetitive transcranial magnetic stimulation frequency, female sex, and the use of first-generation antipsychotics, amisulpride, olanzapine, risperidone, paliperidone, perospirone, and trihexyphenidyl. Negative associations were found with aspartate aminotransferase, fasting plasma glucose, total bilirubin levels, and aripiprazole use. Sex-specific factors included thyroid- stimulating hormone and sulpiride use in men; olanzapine use in women; and differing associations of aspartate aminotransferase, direct bilirubin, age, and urea nitrogen depending on sex. Four female patients developed breast cancer.

Conclusion: Multiple pharmacological and non-pharmacological factors contribute to HPRL in patients with schizophrenia, with notable sex-specific differences. The potential role of HPRL in breast cancer development among female patients requires further investigation.

Introduction: This study aimed to examine the associations among binge eating behaviors (BEBs), emotion regulation (ER), and chronotypes, and whether ER mediates the relationship between chronotypes and BEBs in Greek female university students, a population in which these associations have not previously been investigated.

Methods: This study was approved by the Research and Ethics Committee of the Medical School of Aristotle University of Thessaloniki (No. 91/23, dated 17/02/2023). A total of 269 female students [mean age (±SD) = 21.06 (±4.35)] from Aristotle University of Thessaloniki participated in this cross-sectional study. Participants completed a sociodemographic questionnaire and four validated instruments: the Eating Disorder Examination Questionnaire, the Binge Eating Scale, the Difficulties in Emotion Regulation Scale, and the Morningness-Eveningness Questionnaire.

Results: BEBs were significantly correlated with eating psychopathology (rs = 0.723, p < 0.001) and with difficulties in emotion regulation (ER) (rs = 0.429, p < 0.001). ER difficulties were also associated with eating psychopathology (rs = 0.434, p < 0.001). An evening chronotype was significantly associated with greater ER difficulties (rs = -0.150, 0.014). Mediation analysis indicated that ER difficulties fully mediated the relationship between eveningness and BEBs (Indirect Effect = -0.06, 95% CI: -0.11 to -0.01).

Discussion: ER difficulties are associated with both BEBs and eveningness. While eveningness is not directly associated with BEBs, it is indirectly related through ER difficulties, suggesting a potential psychological mechanism underlying this relationship.

Conclusion: ER difficulties may be a key mechanism linking evening chronotype to BEBs. Future studies could explore whether interventions targeting ER and circadian alignment are beneficial for managing BEBs among individuals with an evening chronotype.

PHLDA1 (pleckstrin homology-like domain family A member 1) is a pleiotropic regulatory protein that affects key biological processes such as apoptosis, pyroptosis, immune inflammation, autophagy, metabolism, and oxidative stress. PHLDA1 plays a significant role in the pathological mechanisms of neurological diseases. This article systematically reviews the molecular characteristics of PHLDA1 and its core role in cerebrovascular diseases such as cerebral ischemia/ reperfusion injury, cerebral hemorrhage, subarachnoid hemorrhage, epilepsy, amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Studies have shown that PHLDA1 promotes disease progression by regulating signalling pathways such as the NF-κB, MAPK, NLRP3 inflammasome, PPARγ, and Nrf2 pathways, thereby exacerbating neuroinflammation, mitochondrial dysfunction, endoplasmic reticulum stress, and pyroptosis in neurons. Its expression is regulated by the dynamic balance of miRNAs (such as miR-194 and miR-101), transcription factors (Egr1 and BHLHE40), and heat shock proteins (HSPs/HSF1). In addition, PHLDA1 has become a potential target for intervention in neurodegenerative and ischemic injuries by inhibiting FundC1-mediated mitochondrial autophagy, regulating microglial polarization, and activating TRAF6-dependent neuroinflammation. This article not only clarifies the pathogenic mechanism of PHLDA1 but also summarizes the relevant intervention strategies targeting PHLDA1, hoping to provide a corresponding theoretical basis and reference for the development of precision therapies for neurological diseases.

Introduction: This study evaluated the safety and effectiveness of efgartigimod in patients with Very-Late-Onset Generalized Myasthenia Gravis (VLOGMG), a population that often presents with more severe symptoms and limited treatment responses.

Methods: Forty-two patients aged ≥ 65 years were retrospectively included. Clinical assessments, including MG activities of Daily Living (MG-ADL), Quantitative Myasthenia Gravis (QMG) scores, prednisone dosage, laboratory data, and adverse events, were recorded at each follow-up.

Results: At week 4, 97.6% (41/42; 95% CI, 87.4-99.9) of patients were MG-ADL responders (≥ 2- point improvement). Notably, 83.3% (95% CI, 69.4-92.8) maintained response through week 12 (p < 0.001). Clinically meaningful improvement (CMI, ≥3-point QMG decrease) occurred in 97.6% of patients (41/42; 95% CI, 87.4-99.9), with a mean response time of 6.37 ± 5.46 days (95% CI, 4.63- 8.11). Minimal symptom expression (MSE, MG-ADL score of 0 or 1) was achieved in 45% (95% CI, 30-61%), 60% (95% CI, 44-74%), and 45% (95% CI, 30-61%) of patients at weeks 4, 8, and 12, respectively. Prednisone dosage was tapered from a median of 20 (20, 30) mg/day to 10 (5, 15) mg/day by week 12. Most patients (88.1%) had ≥ 1 comorbidity, and 61.9% had multimorbidity. Efgartigimod was well tolerated, without evidence of worsening of pre-existing conditions.

Discussion: Efgartigimod provided rapid symptom relief in older adults with VLOGMG and demonstrated steroid-sparing benefits across patients with various comorbidities. The high response rates and sustained improvement suggest that early use of fast-acting therapies may serve as a bridge to conventional long-term treatments. Larger prospective studies are warranted to confirm these findings.

Conclusion: Efgartigimod is associated with clinical benefit in patients with VLOGMG, allowing corticosteroid reduction without compromising comorbidity stability. Early initiation may enable faster disease control and more durable responses.

Ischemic Stroke (IS) is a central nervous system disease caused by cerebrovascular obstruction. It is associated with high mortality and disability rates, few available treatments, and a poor prognosis. Exosomes secreted by neuronal cells have attracted significant attention lately for their roles in maintaining the integrity of the blood-brain barrier, facilitating neuron-to-neuron communication, preventing oxidative stress, and promoting neural regeneration and protection. Therefore, Astrocyte-Derived Extracellular Vesicles (ADEVs), along with their biological characteristics, extraction methods, and identification techniques, are discussed in this review, along with their neuroprotective role and mechanisms in IS and function as specific biomarkers in diagnosis. The purpose of this review is to improve our understanding of the effect of ADEVs in diagnosing and treating IS. In addition, it addresses future goals in IS: precise prognostication of stroke, rapid clinical diagnosis, and the development of new therapies based on exosomes released from brain cells.

Introduction: Preclinical and clinical studies reported that 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') can cause adverse effects in the central nervous system (CNS). Recently, preclinical studies have demonstrated that certain psychoactive substances may exacerbate the noxious central effects of MDMA when co-administered, including substances that are contained as adulterants in tablets sold as MDMA in the illegal market. Since the quality and quantity of adulterants in tablets sold as MDMA vary based on factors, such as the year and the geographical region of production, this may result in diverse health risks for people who use MDMA.

Objectives: This review provides a concise overview of: i) composition of tablets sold as MDMA in Continental Europe, UK, USA and Australia in the post COVID-19 pandemic period; ii) recent preclinical and clinical findings about the central effects of the psychoactive adulterants most commonly found in tablets sold as MDMA in the above areas; and iii) the possible adverse CNS effects of these adulterants in humans when taken in combination with MDMA.

Methods: We systematically searched PubMed, Scopus, and Web of Science for studies published between 2020 and 2025 using terms related to "adulterants", "MDMA tablets composition," "COVID-19". Eligible articles were screened for quality, with emphasis on recent, high-impact contributions. Extracted papers included cytotoxicity studies, neurobehavioral outcomes, and mechanistic insights.

Results: Tablets sold as MDMA are frequently and differently adulterated in Continental Europe, the UK, the USA, and Australia.

Discussion: The possible interactions between MDMA and psychoactive adulterants contained in tablets sold as MDMA deserve attention, since they may potentially explain some of the noxious neurological and psychiatric effects that have been described in people who use MDMA.

Conclusion: Ongoing public health efforts and expansion of drug checking are essential to properly inform MDMA users about the risks associated with psychoactive contaminants, first responders, healthcare professionals, and the general public about the possible detrimental consequences for health associated with the use of MDMA obtained from illicit sources and unintended contaminant consumption.