Journal of neural transmission (Vienna, Austria : 1996)最新文献

{"title":"Health economics of Parkinson's disease prevention: why early detection matters in low- and middle-income countries.","authors":"Roland Dominic G Jamora, Mykha Marie B Tabuzo-Acuin, Norlinah Mohamed Ibrahim, Yoshio Tsuboi","doi":"10.1007/s00702-026-03291-0","DOIUrl":"https://doi.org/10.1007/s00702-026-03291-0","url":null,"abstract":"<p><p>Parkinson's disease (PD) will become the second leading cause of death globally. This rising trend is expected to be even more pronounced in Asia, where six of the most populous countries are located, in countries with a middle socio-demographic index, and in low- to middle-income countries (LMICs) where resources and healthcare system are limited, causing greater public health burden and placing substantial demands to the patient's family, caregiver, community, and the society. The care of patients with PD requires a multidisciplinary approach to manage complex motor and nonmotor symptoms needing a team of specialists, availability of diagnostic tests, and pharmacologic and non-pharmacologic treatments. More often, this approach is not readily available in LMICs and involves a high out-of-pocket expenditure. Improving early detection of both motor and non-motor symptoms facilitate early management, improving quality of life, lessening the economic burden on patients, caregivers, families, and ultimately, the healthcare system.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149009704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progressive micrographia in Parkinson's disease is associated with multidimensional cognitive and motor features.","authors":"Hiroyuki Hamada, Kyohei Mikami, Yoshihiro Itaguchi, Kazuki Yoshida, Atsushi Yamashita, Qi An","doi":"10.1007/s00702-026-03289-8","DOIUrl":"https://doi.org/10.1007/s00702-026-03289-8","url":null,"abstract":"<p><p>Progressive micrographia, characterized by a gradual reduction in handwriting size, is a common yet incompletely understood feature of Parkinson's disease (PD). It has been associated with both motor and cognitive impairment; however, the clinical characteristics associated with progressive micrographia and the relative contributions of motor and cognitive factors remain unclear. This study aimed to investigate the motor, cognitive, and disease-related clinical features associated with progressive micrographia in PD. Thirty-nine individuals with PD underwent handwriting assessment, the Mini-Mental State Examination, the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III, and evaluation of disease duration and levodopa equivalent daily dose. Participants were classified as having progressive micrographia (n = 14) or not having progressive micrographia (n = 25) based on normative handwriting data from healthy older adults. Four machine learning models (logistic regression, elastic net logistic regression, linear support vector machine [SVM], and radial basis function SVM) were evaluated using nested leave-one-out cross-validation. The linear SVM showed the highest numerical area under the receiver operating characteristic curve (AUC; 0.877, 95% CI 0.749-0.977; accuracy = 82.1%). Exploratory feature contribution analyses indicated that classification involved a combination of cognitive and motor features. These findings suggest that progressive micrographia is associated with clinical characteristics extending beyond handwriting impairment alone; however, the identified associations are exploratory and require validation in larger, independent cohorts.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148957791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Excitation/inhibition balance subtypes in autism and their genetic, neural, and clinical profiles.","authors":"Vardan Arutiunian, Catherine A W Sullivan, Megha Santhosh, Emily Neuhaus, Heather Borland, Raphael A Bernier, Susan Y Bookheimer, Mirella Dapretto, Allison Jack, Shafali Jeste, James C McPartland, Adam Naples, John D Van Horn, Kevin A Pelphrey, Sara Jane Webb, Abha R Gupta","doi":"10.1007/s00702-026-03283-0","DOIUrl":"https://doi.org/10.1007/s00702-026-03283-0","url":null,"abstract":"<p><p>Excitation (E)/inhibition (I) imbalance is considered a key mechanism in Autism Spectrum Disorder (ASD). However, E/I imbalance can have different etiologies with increased E relative to I (E > I) and increased I relative to E (E < I). Both neural profiles can be associated with altered clinical phenotype, suggesting \"bell\"-shape brain-behavior relationships. We derived E/I balance measures from resting-state EEG in a large sex-balanced sample of youths with and without autism (N = 310; 164 youths with ASD and 146 typically developing (TD) youths) to address group discriminative power of neural markers, their relation to social skills, and the potential to define different neural subtypes within the autistic group. We also conducted genome-wide copy number variant (CNV) and gene expression analyses to provide additional insight into distinct neural subtypes in autism. A high-density 128-channel electroencephalography (EEG) was used to register neural activity of participants, blood samples were collected from the ASD youths to obtain genomic DNA, and rich behavioral phenotyping was provided for each participant. The results revealed three subgroups within the autistic cohort with the presence of \"typical\" E/I, E > I, and E < I neural profiles. The two subgroups with E/I imbalance had altered clinical phenotypes. In addition, these subgroups had different genetic profiles, showing that genes within identified CNVs had distinct expression patterns with the evidence of more prenatal (E < I) vs. postnatal (E > I) gene expression. The study suggests that the proposed clustering approach has relevance for the identification of clinically meaningful neural and genetic subtypes within a heterogeneous autistic cohort.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148957794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"German Delphi consensus: COMT inhibitors in the management of wearing-off fluctuations in Parkinson's disease.","authors":"W H Jost, R Müller, R Schüle, A Storch, K Witt, L Tönges","doi":"10.1007/s00702-026-03278-x","DOIUrl":"https://doi.org/10.1007/s00702-026-03278-x","url":null,"abstract":"<p><p>COMT inhibitors (COMT-Is) have now been established for thirty years as adjunctive medication in the treatment of Parkinson's disease (PD). When they were first introduced, the prolonged duration of action of levodopa and the increase in levodopa levels were regarded as significant advances. Many questions regarding their practical application have not been fully addressed scientifically. This has led to a degree of uncertainty regarding the assessment of the efficacy and, consequently, the use of COMT-Is. For this reason, the aim of this Delphi consensus was to assess the current status of COMT inhibition in PD in Germany, to identify any shortcomings, and to find new approaches to close our knowledge gaps and reach a consensus on recommendations. In doing so, the authors who formulated the questions for the Delphi consensus aim to provide their colleagues with practical guidance on the use of COMT-Is in the treatment of Parkinson's symptoms. To achieve this aim, 200 specialists in movement disorders across Germany were asked to evaluate 22 statements across three subject areas. 115 specialists responded. Key findings: In topic area 1, 'Response fluctuations and the use of COMT-Is', it emerged that the Wearing-off Questionnaire, 9-item version (WOQ-9) was not unanimously regarded as a suitable tool for diagnosing response fluctuations (agreement rate: 64%). In topic area 2 (role of COMT-Is in the treatment of fluctuations in efficacy), there was a contradiction in that while COMT-Is were not considered the first-line treatment of choice (agreement rate 58%), respondents agreed that they should be used at an early stage when fluctuations in efficacy occur (agreement rate 95%). In topic area 3 (comparison of various aspects of individual COMT-Is), opicapone was unanimously rated as the easiest to manage in daily use due to its once-daily dosing and favourable safety profile (agreement rate: 83%). In summary, the survey provides significant insights into fluctuations diagnosis and the current role of COMT-I in the treatment of PD. The efficacy and tolerability/safety of opicapone observed in clinical trials for the treatment of Parkinson's patients with motor fluctuations are also confirmed in this survey in clinical practice.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148957814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic performance of the Philippine Children's Medical Center clinical criteria for pediatric anti-NMDAR encephalitis: a retrospective validation in a national referral center.","authors":"Santanina I Mendez, Marilyn H Ortiz, Lillian V Lee","doi":"10.1007/s00702-026-03245-6","DOIUrl":"https://doi.org/10.1007/s00702-026-03245-6","url":null,"abstract":"&lt;p&gt;&lt;p&gt; Autoimmune encephalitis cases continue to rise globally. Early recognition, prompt diagnosis and adequate treatment are crucial in improving patient outcomes. However, high cost and limited availability of antibody testing remain a challenge for timely definitive diagnosis. This study evaluated the diagnostic performance of the clinical criteria for pediatric anti-NMDAR (N-methyl-D-aspartate receptor) encephalitis using the Philippine Children's Medical Center (PCMC) Algorithm. A retrospective diagnostic accuracy study was conducted among 160 patients aged 0 to &lt; 19 years admitted at PCMC from 2011 to 2025 with a clinical suspicion of autoimmune encephalitis. Subjects underwent cerebrospinal fluid (CSF) anti-NMDAR antibody testing: 119 tested positive and 41 tested negative. Clinical data were obtained and analyzed to evaluate PCMC algorithm's diagnostic performance using sensitivity, specificity, predictive values and likelihood ratios. Receiver operating characteristic (ROC) analysis and logistic regression were utilized to determine optimal symptom combinations. Of the 160 subjects, abnormal behavior or cognitive dysfunction was the most common symptom. Among CSF anti-NMDAR-positive cases, seizures, movement disorder, and speech dysfunction occurred more frequently than in antibody-negative cases. The number of PCMC clinical symptoms demonstrated acceptable discrimination for anti-NMDAR encephalitis, with an AUC of 0.752 (95% CI 0.666-0.831). A threshold of ≥ 3 symptoms showed high sensitivity but low specificity [sensitivity 94.96% (95% CI 89.35-98.13); specificity 36.59% (95% CI 22.12-53.06)], whereas ≥ 4 symptoms improved specificity with lower sensitivity [sensitivity 63.87% (95% CI 54.55-72.47); specificity 73.17% (95% CI 57.06-85.78)]. Multivariable analysis identified abnormal behavior or cognitive dysfunction, speech dysfunction, seizures, and movement disorder as independent predictors. Symptom combinations including movement disorder showed stronger diagnostic performance. Abnormal behavior plus movement disorder achieved sensitivity of 72.27% (95% CI 63.32-80.08) and specificity of 68.29% (95% CI 51.91-81.92), while seizures plus movement disorder achieved sensitivity of 65.55% (95% CI 56.28-74.02) and specificity of 70.73% (95% CI 54.46-83.87). The triad of abnormal behavior, seizures, and movement disorder provided higher specificity [82.93% (95% CI 67.94-92.85)] with moderate sensitivity [56.30% (95% CI 46.91-65.37)].Overall, the study demonstrates that symptom burden and specific clinical patterns provide strong predictive ability for anti-NMDAR encephalitis in pediatric patients. Among all combinations tested, abnormal behavior, seizures, and movement disorder emerged as the most practical triad, offering the best balance between sensitivity and specificity. It demonstrated high positive predictive value with reasonable specificity for early diagnosis in resource-limited settings. Two- and three-symptom combinations deri","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148914897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping the peripheral sensory dimension of dystonia: a five-axis analysis.","authors":"Anish Mehta, Thyagarajan Shivashanmugam, Michiko K Bruno, Shermyn Neo, Louis C S Tan, Roongroj Bhidayasiri, Sanjay Pandey, Kailash P Bhatia, Pramod Kumar Pal","doi":"10.1007/s00702-026-03285-y","DOIUrl":"https://doi.org/10.1007/s00702-026-03285-y","url":null,"abstract":"<p><p>Dystonia is conventionally attributed to dysfunction in central motor circuits, yet several clinical features, including sensory tricks, task specificity, and abnormalities in somatosensory processing, indicate an influence of sensory input. Whether peripheral sensory afferents are passive conduits to central circuits or contribute to dystonia pathophysiology remains unresolved. To examine whether peripheral sensory afferents participate in dystonia networks beyond their role as upstream inputs. Evidence was synthesized across five domains: phenomenology, electrophysiology, neuroimaging, genetics, and treatment. Priority was given to studies that manipulated or quantified peripheral afferent input and assessed effects on motor output or network physiology. Sensory tricks produce rapid improvement across dystonia phenotypes, indicating that afferent input can influence motor output. Electrophysiological studies demonstrate impaired afferent modulation of intracortical inhibition, abnormal integration of converging sensory inputs, and reduced reflex suppression at spinal and brainstem levels. Neuroimaging studies show somatosensory representations and changes in network activity. Genetic and animal studies implicate dystonia-associated pathways in the regulation of proprioceptive afferent signaling, and sensory-neuron-specific manipulations can induce or reduce abnormal movements. Therapeutic interventions, including peripheral stimulation, botulinum toxin, and sensory blockade, have been associated with reductions in dystonic symptoms through mechanisms that alter afferent input. Findings from phenomenological, electrophysiological, neuroimaging, genetic, and therapeutic studies indicate that peripheral sensory afferents contribute to dystonia networks. These observations are consistent with a model in which abnormalities of afferent gating, sensory integration, and somatosensory representation contribute to dystonic expression across multiple levels of the neuraxis, with potential implications for therapeutic targeting.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148914896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-stratified associations between depressive symptoms and cognitive impairment in treatment-resistant vs. non-resistant schizophrenia.","authors":"Chuhao Zhang, Jingxuan Liu, Jian Zhang, Nannan Liu, Shaobing Li, Xinxu Wang, Yanzhe Li, Chenghao Lu, Jinghui Chi, Yonghui Zhang, Shen Li, Jie Li","doi":"10.1007/s00702-026-03282-1","DOIUrl":"https://doi.org/10.1007/s00702-026-03282-1","url":null,"abstract":"<p><strong>Background: </strong>Treatment-resistant schizophrenia (TRS), affecting approximately 30% of schizophrenia patients, is frequently accompanied by depressive symptoms, which exacerbate cognitive and socio-emotional deficits. However, it remains unclear whether the impact of depressive symptoms on cognition differs by sex in TRS patients.</p><p><strong>Methods: </strong>We evaluated 344 schizophrenia patients (112 TRS, 232 non-TRS) at Tianjin Anding Hospital. Depressive symptoms were assessed with the Hamilton Depression Rating Scale (HAMD), cognitive function with the Repeatable Battery for Neuropsychological Status (RBANS), and alexithymia with the Toronto Alexithymia Scale-26 (TAS-26). Two-way ANCOVA examined diagnosis-by-sex interactions, and partial correlation analyses assessed sex-stratified associations between depressive symptoms and cognitive and emotional measures. FDR correction was applied for all partial correlation analyses.</p><p><strong>Results: </strong>Compared to females, males showed better performance on verbal tasks and higher TAS-26 scores, specifically in identifying, describing, and externally orienting emotions (all p_s < 0.05), but higher levels of hopelessness (p < 0.001). After FDR correction, sex-stratified correlation patterns were observed. In men, depressive measures showed consistent positive correlations with TAS-26 indices (hopelessness-TAS total: r = 0.316, adjusted p < 0.001; total HAMD-DDF: r = 0.291, adjusted p = 0.004), without significant associations with neurocognition. In women, depressive dimensions correlated positively with TAS-26 subscales (anxiety/somatization-DDF: r = 0.256, adjusted p = 0.013) and negatively with multiple RBANS domains (hopelessness-RBANS total: r = - 0.252, adjusted p = 0.013). Stratified analysis by sex and TRS status detected significant depression-TAS-26 correlations only in male TRS patients (hopelessness-TAS total: r = 0.407, adjusted p = 0.050); no meaningful associations survived adjustment in the remaining three subgroups.</p><p><strong>Conclusion: </strong>Our findings indicate that the associations between depressive symptoms and alexithymia differ between males and females in schizophrenia, with distinct patterns observed across TRS and non-TRS patients.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148914938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sublingual apomorphine for Parkinsonian tremor: a post-hoc analysis of pivotal trial data.","authors":"Haidar S Dafsari, João Reis, Kerstin Strauß, Helena C Brigas, Carmen Denecke Muhr, Isabel Pijuan Jiménez, Joerg Holenz","doi":"10.1007/s00702-026-03225-w","DOIUrl":"https://doi.org/10.1007/s00702-026-03225-w","url":null,"abstract":"<p><p>Tremor is a common and disabling feature of Parkinson's disease (PD) and often responds suboptimally to oral dopaminergic therapy. This post‑hoc analysis evaluated tremor outcomes associated with apomorphine sublingual film (SL‑APO) in patients with a tremor‑dominant PD phenotype, using data from a 12‑week randomised, double‑blind, placebo‑controlled trial (NCT02469090) and a 12‑month open‑label study (NCT02542696) conducted in levodopa‑responsive patients with OFF episodes. Tremor‑dominant phenotype was defined according to Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS‑UPDRS) criteria, and tremor severity was assessed using a derived tremor index. In the randomised trial, 31 of 108 patients (28.7%) met tremor‑dominant criteria. At Week 12 (n = 10 per group), greater reductions in tremor index scores were observed 30 min post‑dose with SL‑APO versus placebo (mean change - 5.3 vs. - 1.1), with an exploratory between‑group difference of - 4.4 (p < 0.001) and an effect size (Cohen's d) of - 1.83. Clinically important improvement occurred more frequently with SL‑APO (80%) than placebo (30%), corresponding to an estimated number needed to treat of 1.3. Median time to ON with SL‑APO was 13.0 min. In the open‑label study, tremor reductions of 31-37% were maintained over 12 months, with responder rates remaining above 70%. These exploratory findings in a small subgroup are consistent with a potential for early and maintained tremor improvement with SL‑APO in patients with tremor‑dominant PD; however, the results are hypothesis‑generating and require prospective confirmation.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148914934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atypical sensory traits and changes in white matter microstructures connected to the amygdala and hippocampus of the autistic brain.","authors":"Taku Kamiya, Kaie Habata, Yongjeon Cheong, Daichi Shiotsu, Takuya Makino, Kotaro Kowada, Riku Sanada, Ichiro M Omori, Sohei Ide, Hidehiko Okazawa, Minyoung Jung, Hirotaka Kosaka","doi":"10.1007/s00702-026-03264-3","DOIUrl":"https://doi.org/10.1007/s00702-026-03264-3","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) is characterized by atypical sensory traits. The amygdala and hippocampus have been implicated in ASD, but how sensory traits relate to white matter pathways connected to these regions remains unclear. We therefore examined whether sensory traits are associated with microstructural properties of amygdala- and hippocampus-connected white matter in adults with ASD. We included 40 adults with ASD and 83 typically developing (TD) adults (all aged ≥ 18 years). Participants completed the Adolescent/Adult Sensory Profile (AASP) and underwent diffusion tensor imaging. Diffusion metrics were computed for bilateral amygdala-connected white matter (AWM) and hippocampus-connected white matter (HWM). The ASD group showed lower fractional anisotropy (FA) in both AWM and HWM than the TD group. In the ASD group, sensation-seeking scores revealed a nominal positive association with FA in the right AWM, although this association did not survive FDR correction. In the TD group, sensation-seeking scores were negatively associated with FA in the right HWM. Fisher r-to-z tests with FDR correction indicated significant group differences in the associations between sensation seeking and FA of the right AWM and right HWM. White matter microstructure in pathways connected to the amygdala and hippocampus showed group differences in FA and in how FA related to sensation seeking. These findings suggest that atypical sensory traits in ASD may be linked to microstructural differences in amygdala- and hippocampus-connected pathways.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148914929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of memantine in adults with amyotrophic lateral sclerosis: a systematic review and meta-analysis.","authors":"Lara Hamzeh Hamzeh, Enas Seyed, Mena Ayman Elgendy, Daher Heib, Beshoy I Sadek, Chalak O S Mohammed, Karima El Refaei, Yara F Soliman, Nora Eldmrdash, Mahmoud Shaaban Abdelgalil, Mahmoud M Elsayed","doi":"10.1007/s00702-026-03281-2","DOIUrl":"https://doi.org/10.1007/s00702-026-03281-2","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with limited disease-modifying treatment options. Memantine, an N-methyl-D-aspartate receptor antagonist, has been investigated in ALS, but its safety remains unclear. This study systematically assessed the safety of memantine in adults with ALS. A systematic review and meta-analysis was conducted following PRISMA 2020 guidelines, searching PubMed, Cochrane Library, Scopus, and Web of Science for randomized controlled trials of memantine in adults with ALS. Outcomes included ALSFRS-R and FVC decline, adverse neurological events, total and serious adverse events, treatment discontinuation, and all-cause mortality. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Because of heterogeneous reporting and missing variance estimates, ALSFRS-R and FVC outcomes were synthesized narratively; only safety outcomes were pooled quantitatively. Three randomized controlled trials (706 participants) met the inclusion criteria. Functional and respiratory outcomes could not be pooled because of heterogeneous reporting, and no consistent benefit was observed. Memantine showed lower headache incidence than placebo (RR 0.43; 95% CI 0.19-0.96), with no significant differences in constipation, falls, dizziness, treatment discontinuation, or all-cause mortality. Memantine showed a borderline increase in serious adverse events (RR 1.52; 95% CI 1.00-2.31) and a higher risk of total adverse events (RR 1.19; 95% CI 1.09-1.30). Memantine was associated with a small but significant increase in total adverse events and a trend toward more serious adverse events, without improving functional decline, respiratory function, or survival in ALS. Current evidence does not support its use as a disease-modifying or adjunctive therapy. Trial registration: PROSPERO CRD420261277874.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148914908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}