Journal of Neural Transmission最新文献

{"title":"Usability of the digit-tracking technique in a geriatric population of inpatients with and without neurocognitive disorders: The DIGICOG-start study.","authors":"Grégory Ben-Sadoun, Lena Carcreff, Guillaume Sacco, Frédéric Noublanche, Cédric Annweiler","doi":"10.1007/s00702-024-02858-z","DOIUrl":"10.1007/s00702-024-02858-z","url":null,"abstract":"<p><p>Tools for the early diagnosis of neurocognitive disorders (NCD) both accessible, fast, fun and efficient are currently needed. A digit-tracking technique (Digitrack) has been developed based on the exploration of blurred images on a tablet with the finger, related to the exploration of images during eye-tracking. The present study aimed at assessing the objective usability and the subjective User eXperience (UX) of the Digitrack by older adults according to the presence and the severity of NCD. A total of 135 patients were included in a geriatric acute care unit. Objective usability was assessed through the number of patients able to complete the Digitrack's training (3 images) and evaluation (20 images) phases. UX was measured through standard questionnaires (AttrakDiff and meCUE), and through the description of engagement behaviors following an internally developed scale which included 5 levels (interactive, constructive, active, passive and disengaged behaviors). The success rate of the device was 94.1%. The Digitrack had a very good overall attractiveness, standard hedonic and pragmatic qualities, and the emotions perceived were predominantly positive. These findings were not homogeneously observed in the whole studied population. Patients highly impaired due to NCD tended to rate the device with more neutral scores and to perceive more negative emotions. The participants mainly demonstrated active behaviors, but patients with severe major NCD were mostly passive. The study showed promising results regarding the usability and acceptability of a digit-tracking technique within older adults. Further studies should evaluate the potential of this novel methods to make a cognitive diagnosis.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":"469-483"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of safinamide in Parkinson's disease patients with motor fluctuations without levodopa dosage escalation over 18 weeks: KEEP study.","authors":"Eungseok Oh, Sang-Myeong Cheon, Jin Whan Cho, Young Hee Sung, Joong-Seok Kim, Hae-Won Shin, Jong-Min Kim, Mee Young Park, Do-Young Kwon, Hyeo Ma, Jeong-Ho Park, Seong-Beom Koh, Seong-Min Choi, Jinse Park, Phil Hyu Lee, Tae-Beom Ahn, Sang Jin Kim, Chul Hyoung Lyoo, Ho-Won Lee, Jieun Kim, Yoona Lee, Jong Sam Baik","doi":"10.1007/s00702-024-02851-6","DOIUrl":"10.1007/s00702-024-02851-6","url":null,"abstract":"<p><p>This multicentre, prospective, single-arm study evaluated safinamide as add-on therapy to levodopa in Korean patients with Parkinson's disease (PD) with motor fluctuations with ≥ 1.5 h of \"off\" time daily, who took levodopa ≥ 3 times/day (n = 199). Baseline levodopa and dopamine agonist doses were maintained without escalation during the 18-week treatment period. Participants received safinamide 50 mg/day for 2 weeks and 100 mg/day thereafter. PD diaries and questionnaires (Parkinson's Disease Questionnaire, PDQ-39; Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale, MDS-UPDRS part 3 and part 4; King's Parkinson's Disease Pain Scale, KPPS; Mini-Mental State Examination, MMSE) were assessed at baseline and at week 18. Treatment-emergent adverse events (TEAEs) were recorded. Mean disease duration was 6.6 years, and mean levodopa equivalent daily dose was 721.1 mg/day. At week 18, significant improvements from baseline were seen for the co-primary endpoints, mean daily \"off\" time (- 1.3 ± 2.4 h, p < 0.001) and quality of life (QoL) based on PDQ-39 summary index (- 2.7 ± 10.3, p < 0.001), Moreover, significant improvements were seen in motor symptoms and motor complications (MDS-UPDRS part 3 and 4), daily \"on\" time without dyskinesia (all p < 0.001) and pain (KPPS; p = 0.013). TEAEs occurred in 40.2% of patients, with most being mild in severity. In conclusion, safinamide at a dosage of 100 mg/day significantly improved motor symptoms, QoL, and pain, and demonstrated a favourable safety profile without levodopa dosage escalation during the 18-week treatment period in Korean patients with PD.Trial registration number and date: NCT05312632, First Posted: April 5, 2022.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":"431-441"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11870872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insulin signaling disruption exacerbates memory impairment and seizure susceptibility in an epilepsy model with Alzheimer's disease-like pathology.","authors":"Suélen Santos Alves, Gabriel Servilha-Menezes, Letícia Rossi, José Antonio Cortes de Oliveira, Mariana Grigorio-de-Sant'Ana, Adriano Sebollela, Rui Milton Patrício da Silva-Junior, Norberto Garcia-Cairasco","doi":"10.1007/s00702-025-02896-1","DOIUrl":"https://doi.org/10.1007/s00702-025-02896-1","url":null,"abstract":"<p><p>Alzheimer's disease (AD) and epilepsy exhibit a complex bidirectional relationship. Curiously, diabetes as a comorbidity increases the risk of epilepsy among AD patients. Recently, we reported that the Wistar audiogenic rat (WAR) strain, a genetic model of epilepsy, displays a partial AD-like phenotype, including brain insulin resistance. We also assessed seizure susceptibility in an AD model created through intracerebroventricular injections of streptozotocin (icv-STZ), which induces AD features via brain insulin resistance. Our goal was to explore how disrupted brain insulin signaling influences AD-like features and seizure susceptibility in the WAR strain. Adult male WARs received a single intracerebroventricular injection of streptozotocin (icv-STZ) (1.5 mg/kg) or vehicle (saline). Two weeks post-injection, spatial memory was assessed using the Barnes Maze (BM) test. Three weeks later, the rats underwent an audiogenic kindling (AuK) protocol (20 acoustic stimuli, 2 per day) to evaluate seizure frequency and severity. Seizures were analyzed using the Categorized Severity Index and Racine's scale and Western blot analysis was performed on hippocampal tissue. Our findings revealed that icv-STZ significantly worsened memory performance, increased seizure frequency, and reduced seizure onset relative to vehicle. Furthermore, icv-STZ decreased Akt activation and increased Glycogen Synthase Kinase-3 (GSK3) phosphorylation, indicating disrupted insulin signaling. Notably, icv-STZ decreased tau phosphorylation without altering amyloid β precursor protein (AβPP) levels. In conclusion, a low-dose icv-STZ injection exacerbates memory deficits and seizure susceptibility in the WAR strain by disturbing downstream proteins involved in insulin signaling. This highlights the implications of brain insulin resistance in both AD and epilepsy.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unusual delayed and prolonged arm weakness and atrophy following botulinum toxin injection for musician's cramp: case report.","authors":"Barbara I Karp, Katharine Alter, Tanya Lehky, Mark Hallett","doi":"10.1007/s00702-024-02864-1","DOIUrl":"https://doi.org/10.1007/s00702-024-02864-1","url":null,"abstract":"<p><p>Botulinum toxin is considered first-line treatment for focal hand dystonia in musicians. Mild, temporary weakness is a common accompaniment of effective injection. We present a unique case of delayed-onset, severe, prolonged weakness and atrophy in a patient with musician's dystonia, successfully treated with botulinum toxin for over 10 years, following injection of his usual muscles at his well-established dose. This pianist received botulinum toxin treatment for more than 10 years, with a stable response. Six weeks after an injection, he developed progressive severe weakness and atrophy of the affected forearm involving both injected and uninjected muscles. Weakness and atrophy took over one year without further injections to resolve. The clinical course and laboratory testing were not suggestive of brachial neuritis, plexopathy, or neuralgic amyotrophy. The literature contains rare case reports of severe weakness and atrophy after botulinum toxin injection, sometimes with delayed onset and sometimes affecting distant muscles. Frequently presenting with pain, such cases often have evidence of plexopathy or neuralgic amyotrophy which were absent in our patient. Clinicians should be aware of this rare potential severe adverse event associated with botulinum toxin.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non motor Parkinson: subtypes, biomarkers, stepped care and a journal!","authors":"K Ray Chaudhuri, Karolina Poplawska-Domaszewicz, Indu Subramanian, Wolfgang H Jost","doi":"10.1007/s00702-025-02895-2","DOIUrl":"https://doi.org/10.1007/s00702-025-02895-2","url":null,"abstract":"","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptional dysregulation in the cerebellum triggered by oligodendroglial α-synucleinopathy: insights from a transgenic mouse into the early disease mechanisms of MSA.","authors":"Antonio Heras-Garvin, Lisa Fellner, Roberta Granata, Gregor K Wenning, Nadia Stefanova","doi":"10.1007/s00702-025-02892-5","DOIUrl":"https://doi.org/10.1007/s00702-025-02892-5","url":null,"abstract":"<p><p>Multiple system atrophy (MSA) is a fatal neurodegenerative disorder characterized by abnormal accumulation of α-synuclein, progressive neuronal loss, motor impairment and widespread pathological changes, which include significant involvement of the cerebellum. To understand the early molecular mechanisms that might underlie α-synuclein-triggered MSA cerebellar pathology, we performed RNA sequencing (RNA-Seq) of cerebellar samples from a well-established model of MSA. RNA-Seq and differential gene expression analysis was conducted in the PLP-αSyn model of MSA. Cerebellum from two and 12-month-old MSA and wildtype mice were used. Gene ontology (GO) and KEGG enrichment analyses of the differentially expressed genes (DEGs) were performed to explore processes involved in MSA-like disease progression. The overlap between transcriptional changes in MSA and those associated with aging was also evaluated. RNA-Seq analysis demonstrated significant transcriptional dysregulation in cerebellum from MSA mice, even at early stages. GO and KEGG analyses of DEGs point to a potential role of synaptic dysfunction, cellular signaling dysregulation and inflammation in the cerebellar pathology of MSA mice. In addition, those changes exacerbate with disease progression. Additionally, our analysis of aging in both control and PLP-αSyn mice showed that age-related transcriptional changes in mid-aged controls seem to be present in young MSA mice. Thus, MSA-like pathology might lead to an acceleration of aging-related mechanisms. Our findings demonstrate significant cerebellar transcriptional dysregulation triggered by oligodendroglial α-synucleinopathy in PLP-αSyn mice, revealing pathways that might be critical for the early cerebellar pathology of MSA, and that may serve as potential molecular targets for therapeutic interventions in this devastating disorder.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein misfolding: understanding biology to classify and treat synucleinopathies.","authors":"Tiago Fleming Outeiro, Günter Höglinger, Anthony E Lang, Tuane C R G Vieira","doi":"10.1007/s00702-025-02889-0","DOIUrl":"https://doi.org/10.1007/s00702-025-02889-0","url":null,"abstract":"<p><p>Protein misfolding and aggregation is a major pathological hallmark in a variety of human conditions, including cancer, diabetes, and neurodegeneration. However, we still do not fully understand the role of protein accumulation in disease. Interestingly, recent breakthroughs in artificial intelligence (AI) are having a tremendous impact on our ability to predict three-dimensional protein structures and understand the molecular rules governing protein folding/misfolding. This progress will enable us to understand how intrinsic and extrinsic factors trigger protein misfolding, thereby changing protein function. These changes, in some cases, are related to normal biological responses and, in other cases, associated with pathological alterations, such as those found in many neurodegenerative disorders. Here, we provide a brief historical perspective of how findings in the field of prion diseases and prion biology have enabled tremendous advances that are now forming the basis for our understanding of disease processes and discuss how this knowledge is now emerging as central for our ability to classify, diagnose, and treat devastating neurodegenerative disorders such as Parkinson's and Alzheimer's diseases.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the interplay of glucose metabolism, insulin resistance, and neurodegenerative pathologies: insights from streptozotocin and hypoglycaemic in vitro models.","authors":"Edna Grünblatt, Cristine Marie Yde Ohki, G Angelika Schmitt-Böhrer, Peter Riederer, Susanne Walitza","doi":"10.1007/s00702-025-02891-6","DOIUrl":"https://doi.org/10.1007/s00702-025-02891-6","url":null,"abstract":"<p><p>Neurodegenerative diseases raise public health concerns. Recent evidence indicates that Alzheimer's disease (AD) sufferers will triple by 2050. The rising incidence of dementia diagnoses raises concerns about the socio-economical and emotional impact of this uncurable illness, which reduces quality of life through cognitive decline. Although genetic and environmental factors may contribute to its aetiology, neuropathological mechanisms underlying these disorders are still under investigation. One is brain insulin resistance (BIR), which has been associated with clinical cognitive dysfunction and linked to mitochondrial dysfunction, neurogenesis deficits, and cell death. Not limited to neurodegeneration, these phenotypes have been associated with other neuropsychiatric disorders. Streptozotocin (STZ), a diabetes-causing drug that targets pancreatic β-cells, may imitate BIR in suitable models. From patients' neuroimaging to in vitro approaches, scientists have been striving to understand the pathophysiology of such disorders at the behavioural, molecular, and cellular levels. Although animal models are useful for studying insulin resistance's systemic effects, in vitro phenotypic research represents an alternative to study molecular and cellular aspects. STZ and hypoglycaemia-like scenarios have been successful for studying neurodegenerative disorders in primary cell culture (e.g., neuroblastoma cells) and patient-specific neural cell lines derived from pluripotent stem cells (iPSCs). Intriguingly, STZ treatment or hypoglycaemia-like conditions in a dish were able to induce AD pathological characteristics such Aβ plaque deposition and Tau protein hyperphosphorylation. Such approaches have shown potential in understanding molecular and cellular implications of metabolic changes in neuropsychiatric disorders, according to this review. Furthermore, these models may help identify novel treatment targets.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The spectrum of behavioral disorders in amyotrophic lateral sclerosis: current view.","authors":"Kurt A Jellinger","doi":"10.1007/s00702-024-02841-8","DOIUrl":"10.1007/s00702-024-02841-8","url":null,"abstract":"<p><p>Behavioral disorders, with an average prevalence of 30-60% are important non-motor symptoms in amyotrophic lateral sclerosis (ALS) that have a negative impact on prognosis, management and quality of life, yet the underlying neurobiology is poorly understood. Among people with ALS, apathy, fatigue, anxiety, irritability and other behavioral symptoms are the most prominent, although less frequent than cognitive impairment. The present review explores the current understanding of behavioral changes in ALS with particular emphasis on our current knowledge about their structural and functional brain correlates, substantiating a multisystem degeneration with particular dysfunction of frontal-subcortical circuits and dysfunction of fronto-striatal, frontotemporal and other essential brain systems. The natural history of behavioral dysfunctions in ALS and their relationship to frontotemporal lobe degeneration (FTLD) are not fully understood, although they form a clinical continuum, suggesting a differential vulnerability of non-motor brain networks, ALS being considered a brain network disorder. An assessment of risks or the early detection of brain connectivity signatures before structural changes may be helpful in investigating the pathophysiological mechanisms of behavioral impairment in ALS. Treatment of both ALS and co-morbid behavioral disorders is a multidisciplinary task, but whereas no causal or disease-modifying therapies for ALS are available, symptomatic treatment of a variety of behavioral symptoms plays a pivotal role in patient care, although the management of behavioral symptoms in clinical care still remains limited.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":"217-236"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The corticospinal tract in multiple sclerosis: correlation between cortical excitability and magnetic resonance imaging measures.","authors":"Paul Kauv, Moussa A Chalah, Alain Créange, Jean-Pascal Lefaucheur, Jérôme Hodel, Samar S Ayache","doi":"10.1007/s00702-024-02849-0","DOIUrl":"10.1007/s00702-024-02849-0","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a central nervous system disease involving gray and white matters. Transcranial magnetic stimulation (TMS) and magnetic resonance imaging (MRI) could help identify potential markers of disease evolution, disability, and treatment response. This work evaluates the relationship between intracortical inhibition and facilitation, motor cortex lesions, and corticospinal tract (CST) integrity. Consecutive adult patients with progressive MS were included. Sociodemographic and clinical data were collected. MRI was acquired to assess primary motor cortex lesions (double inversion and phase-sensitive inversion recovery) and CST integrity (diffusion tensor imaging). TMS outcomes were obtained: motor evoked potentials (MEP) latency, resting motor threshold, short-interval intracortical facilitation (ICF) and inhibition. Correlation analysis was performed. Twenty-five patients completed the study (13 females, age: 55.60 ± 11.49 years, Expanded Disability Status Score: 6.00 ± 1.25). Inverse correlations were found between ICF mean and each of CST radial diffusivity (RD) (ρ =-0.56; p < 0.01), CST apparent diffusion coefficient (ADC) (ρ=-0.44; p = 0.03), and disease duration (ρ=-0.46; p = 0.02). MEP latencies were directly correlated with disability scores (ρ = 0.55; p < 0.01). High ADC/RD and low ICF have been previously reported in patients with MS. While the former could reflect structural damage of the CST, the latter could hint towards an aberrant synaptic transmission as well as a depletion of facilitatory compensatory mechanisms that helps overcoming functional decline. The findings suggest concomitant structural and functional abnormalities at later disease stages that would be accompanied with a heightened disability. The results should be interpreted with caution mainly because of the small sample size that precludes further comparisons (e.g., treated vs. untreated patients, primary vs. secondary progressive MS). The role of these outcomes as potential MS biomarkers merit to be further explored.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":"265-273"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}