Current Neuropharmacology - Online First

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

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

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.

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.

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

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.

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.

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.

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.

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.

Preclinical and clinical studies reported that 3,4-methylenedioxymeth-amphetamine (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.

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.

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.

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

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.

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.

Medical cannabis has gained growing attention as a potential treatment for children with Autism Spectrum Disorder (ASD), particularly in cases where conventional pharmacological approaches have proven ineffective. Emerging evidence suggests that cannabinoid-based therapies may alleviate Attention Deficit Hyperactivity Disorder (ADHD) related symptoms in children with ASD. The objective of this study is to evaluate changes in ADHD symptoms over six months of treatment with a CBD-rich cannabis oil, using the Conners' Teacher Rating Scale as the assessment tool.

This was a prospective, single-arm, open-label study conducted at a single center. A total of 109 children and young adults diagnosed with ASD and ADHD symptoms were recruited between November 2019 and April 2021. Of these, 53 participants were assessed by their schoolteachers using the Conners' Teacher Rating Scale (CTRS) questionnaire, both before and after a three- to six-month treatment period with a CBD-rich, cannabis oil-based product. Blood samples were collected before and after treatment to measure cannabinoid levels, including CBD, 6-OH-CBD, 7-COOH-CBD, and 7-OH-CBD.

Significant improvements were observed in the following categories: anxious-shyness, perfectionism, ADHD index, emotional lability, and hyperactivity-impulsivity (p < 0.001). Additional trends toward improvement were identified in oppositional behavior (p = 0.009), cognitive inattention (p = 0.009), hyperactivity (p = 0.006), the Conners’ Global Index (p = 0.007), and DSM-IV inattention scores (p = 0.003). No significant correlations were found between cannabinoid dosage or blood levels and changes in CTRS scores, except for emotional lability, where higher CBD concentrations were predictive of greater symptom improvement.

This is the first prospective study to evaluate the effects of CBD-rich cannabis on ADHD symptoms in children with ASD using standardized teacher-based Assessments (CTRS). The findings indicate improvements in core behavioral domains. While previous studies have focused primarily on parent-reported outcomes or small-scale trials, our results support emerging evidence on the role of cannabinoids in modulating attention and emotional regulation. The main limitations of the study were its open-label design.

CBD-rich cannabis oil may reduce ADHD symptoms in children with ASD. These findings support the need for future clinical trials to validate efficacy and determine optimal dosing.

To investigate hemodynamic and blood oxygen metabolism and their associations with disease progression, dopaminergic transporter (DAT) activity, and glucose uptake in patients with Parkinson’s disease (PD).

This cross-sectional study included 73 patients with PD (mean age: 61.10 years) and 67 healthy controls (mean age: 58.99 years). Oxygen metabolism parameters—deoxygenated hemoglobin (Cdeoxy), oxygen extraction fraction (OEFrel), deoxygenated cerebral blood volume (dCBV), and R2* were measured using qMRI. DAT availability and glucose metabolism were assessed using PET with [18F]FP-CIT and [18F]FDG, respectively. Regional analyses were conducted using standardized brain atlases.

Compared with the controls patients with PD exhibited elevated Cdeoxy, OEFrel, and R2* in the substantia nigra, whereas Cdeoxy and dCBV levels were reduced in the bilateral caudate nucleus and frontal cortex (p < 0.05). The Hoehn-Yahr (H-Y) 2.5–3 subgroup exhibited higher levels of Cdeoxy and OEFrel in the left putamen than the H-Y 1-2 subgroup (p < 0.05). In the H-Y 1-2 subgroup, Cdeoxy, OEFrel, and R2* correlated with UPDRS scores in the substantia nigra and red nucleus (p < 0.05). In advanced stages (H-Y stages 2.5-3), significant correlations were observed in the striatal structures/the left dorsolateral putamen/posterior right caudate (p < 0.05). OEFrel and R2* values were positively correlated with glucose metabolism in the left putamen and right caudate. (p < 0.05).

qMRI demonstrated alterations in hemodynamics and oxygen metabolism in patients with PD, particularly within the nigrostriatal system, suggesting that metabolic indicators could serve as supplementary biomarkers for diagnosing and monitoring the progression of PD.

Neural regeneration remains a highly debated topic, yet it lacks a systematic bibliometric analysis. The objective of this study is to utilize bibliometric methods to identify research trends and significant topics within this domain, thereby providing a comprehensive overview of the current state of knowledge in this field.

The Web of Science Core Collection (January 1, 2015 to October 3, 2024) served as the basis for analyzing 3,941 documents using CiteSpace and VOSviewer. The analysis focused on country/institution collaboration networks, keyword co-occurrence, and hotspot evolution.

Between 2015 and 2024, the number of publications in this field demonstrated an upward trend, characterised by fluctuations. China and the United States were the leading contributors to global research output, with China contributing 1,387 papers, accounting for 35.19% of the total, and boasting an H-index of 62. In contrast, the United States contributed 1,047 papers, with an h-index of 74. In recent years, research has been concentrated on four major technological directions, including neural electrical stimulation, biomaterial scaffolds, gene editing, and neural modulation.

This transformation in scholarly focus reflects the convergence of multiple catalytic factors, which have enabled the sophisticated simulation of neural systems, provided unprecedented analytical tools for neuroscience inquiry, and intensified societal demands for artificial intelligence applications and neurotechnology innovations, thereby stimulating accelerated research investment.

Over the past decade, researchers worldwide have focused on neural regeneration. Bibliometric analyses have assessed scholarship, identified research hotspots, summarized core concepts, and provided valuable insights for future research in this field.

Treatment-resistant depression (TRD) is a severe psychiatric condition that may increase the risk of suicidal thoughts and self-harming behaviors. Intranasal esketamine has emerged as an effective treatment for TRD, also addressing depression-related emergencies such as suicidal ideation.

This retrospective observational study analyzed 26 outpatients with TRD treated with adjunctive intranasal esketamine alongside ongoing oral antidepressants for 4 weeks. Suicidal ideation and behaviors were assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS), and depressive symptoms were evaluated with the Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline, week 2, and week 4. Statistical analyses included repeated-measures ANOVA and subgroup analyses by gender and baseline self-harm profile.

Esketamine significantly reduced suicidal ideation and depressive symptoms from baseline to week 2 and week 4 (all p<.001). Additionally, non-suicidal self-harm declined, exhibiting gender-specific patterns: women demonstrated a faster reduction in non-suicidal self-harm, whereas men showed slower improvement in suicidal self-harm. A strong correlation between depressive symptoms and suicidality confirmed their interplay.

In our real-world TRD sample, adjunctive intranasal esketamine led to a rapid and sustained reduction in suicidality and depressive symptoms, with distinct gender-related patterns in self-harm trajectories. These findings may inform individualized monitoring strategies. Limitations include the small sample size, retrospective design, and lack of a control group.

Esketamine rapidly improved suicidality and depression in TRD, with preliminary evidence suggesting gender-specific responses, and highlighting the importance of tailored interventions to maximize outcomes. Further research is needed to confirm these differences, explore the long-term effects, and understand the underlying mechanisms.