Journal of Neural Transmission最新文献

{"title":"Revolutionizing our understanding of Parkinson's disease: Dr. Heinz Reichmann's pioneering research and future research direction.","authors":"Masaru Tanaka, László Vécsei","doi":"10.1007/s00702-024-02812-z","DOIUrl":"10.1007/s00702-024-02812-z","url":null,"abstract":"<p><p>Millions of individuals around the world are afflicted with Parkinson's disease (PD), a prevalent and incapacitating neurodegenerative disorder. Dr. Reichmann, a distinguished professor and neurologist, has made substantial advancements in the domain of PD research, encompassing both fundamental scientific investigations and practical applications. His research has illuminated the etiology and treatment of PD, as well as the function of energy metabolism and premotor symptoms. As a precursor to a number of neurotransmitters and neuromodulators that are implicated in the pathophysiology of PD, he has also investigated the application of tryptophan (Trp) derivatives in the disease. His principal findings and insights are summarized and synthesized in this narrative review article, which also emphasizes the challenges and implications for future PD research. This narrative review aims to identify and analyze the key contributions of Reichmann to the field of PD research, with the ultimate goal of informing future research directions in the domain. By examining Reichmann's work, the study seeks to provide a comprehensive understanding of his major contributions and how they can be applied to advance the diagnosis and treatment of PD. This paper also explores the potential intersection of Reichmann's findings with emerging avenues, such as the investigation of Trp and its metabolites, particularly kynurenines, which could lead to new insights and potential therapeutic strategies for managing neurodegenerative disorders like PD.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":"1367-1387"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11608389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897587","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":"In situ stoichiometry amounts of p62 and poly-ubiquitin exceed the increase of alpha-synuclein during degeneration of catecholamine cells induced by autophagy inhibition in vitro.","authors":"Paola Lenzi, Gloria Lazzeri, Michela Ferrucci, Carla Letizia Busceti, Stefano Puglisi-Allegra, Francesco Fornai","doi":"10.1007/s00702-024-02795-x","DOIUrl":"10.1007/s00702-024-02795-x","url":null,"abstract":"<p><p>Neurodegenerative disorders are typically featured by the occurrence of neuronal inclusions. In the case of Parkinson's disease (PD) these correspond to Lewy bodies (LBs), which are routinely defined as proteinaceous inclusions composed of alpha-synuclein (alpha-syn). In turn, alpha-syn is considered to be the key protein in producing PD and fostering its progression. Recent studies challenged such a concept and emphasized the occurrence of other proteins such as p62 and poly-ubiquitin (Poly-ub) in the composition of LBs, which are also composed of large amounts of tubulo-vesicular structures. All these components, which accumulate within the cytosol of affected neurons in PD, may be the consequence of a dysfunction of major clearing pathways. In fact, autophagy-related systems are constantly impaired in inherited PD and genetic models of PD. The present study was designed to validate whether a pharmacological inhibition of autophagy within catecholamine cells produces cell damage and accumulation of specific proteins and tubulo-vesicular structures. The stoichiometry counts of single proteins, which accumulate within catecholamine neurons was carried out along with the area of tubulo-vesicular structures. In these experimental conditions p62 and Poly-ub accumulation exceeded at large the amounts of alpha-syn. In those areas where Poly-ub and p62 were highly expressed, tubulo-vesicular structures were highly represented compared with surrounding cytosol. The present study confirms new vistas about LBs composition and lends substance to the scenario that autophagy inhibition rather than a single protein dysfunction as key determinant of PD.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":"1397-1414"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11608283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419590","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":"Impaired dual-task gait in Parkinson's disease is associated with brain morphology changes.","authors":"Radim Krupička, Christiane Malá, Slávka Neťuková, Tereza Hubená, Filip Havlík, Ondrej Bezdicek, Petr Dušek, Evžen Růžička","doi":"10.1007/s00702-024-02758-2","DOIUrl":"10.1007/s00702-024-02758-2","url":null,"abstract":"<p><p>In Parkinson's disease (PD), impaired gait and cognition affect daily activities, particularly in the more advanced stages of the disease. This study investigated the relationship between gait parameters, cognitive performance, and brain morphology in patients with early untreated PD. 64 drug-naive PD patients and 47 healthy controls (HC) participated in the study. Single- and dual-task gait (counting task) were examined using an expanded Timed Up & Go Test measured on a GaitRite walkway. Measurements included gait speed, stride length, and cadence. A brain morphometry analysis was performed on T1-weighted magnetic resonance (MR) images. In PD patients compared to HC, gait analysis revealed reduced speed (p < 0.001) and stride length (p < 0.001) in single-task gait, as well as greater dual-task cost (DTC) for speed (p = 0.007), stride length (p = 0.014) and cadence (p = 0.029). Based on the DTC measures in HC, PD patients were further divided into two subgroups with normal DTC (PD-nDTC) and abnormally increased DTC (PD-iDTC). For PD-nDTC, voxel-based morphometric correlation analysis revealed a positive correlation between a cluster in the left primary motor cortex and stride-length DTC (r = 0.57, p = 0.027). For PD-iDTC, a negative correlation was found between a cluster in the right lingual gyrus and the DTC for gait cadence (r=-0.35, p_FWE = 0.018). No significant correlations were found in HC. The associations found between brain morphometry and gait performance with a concurrent cognitive task may represent the substrate for gait and cognitive impairment occurring since the early stages of PD.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":"1389-1395"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11608385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139983132","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":"Facets of movement disorders- a tribute to Heinz Reichmann.","authors":"Peter Riederer, Etienne C Hirsch","doi":"10.1007/s00702-024-02857-0","DOIUrl":"10.1007/s00702-024-02857-0","url":null,"abstract":"","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":"1363-1365"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583237","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":"Cognitive impairment in Parkinson's disease and other parkinsonian syndromes.","authors":"Alexandros Giannakis, Chrissa Sioka, Eugenia Kloufetou, Spiridon Konitsiotis","doi":"10.1007/s00702-024-02865-0","DOIUrl":"https://doi.org/10.1007/s00702-024-02865-0","url":null,"abstract":"<p><p>In this narrative review, we address mild cognitive impairment, a frequent complication of Parkinson's disease (PD) and atypical parkinsonian disorders (APDs). Recent diagnostic criteria have blurred the lines between PD and dementia with Lewy bodies (DLB), particularly in the cognitive domain. Additionally, atypical parkinsonian syndromes like progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) often present with significant cognitive decline. Even multiple system atrophy (MSA) can be associated with cognitive impairment in some cases. Several biomarkers, including imaging techniques, such brain magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET), as well as pathological proteins either of the cerebrospinal fluid (CSF), such as Tau, amyloid beta, and synuclein, or of the serum, such as neurofilament light chain (Nfl) are more and more often utilized in the early differential diagnosis of APDs. The complex interplay between these conditions and the evolving understanding of their underlying pathologies highlight the need for further research to refine diagnostic criteria, possibly incorporate the new findings from the biomarker's field into the diagnostic criteria and develop targeted therapeutic strategies.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769873","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":"Effect of subthalamic and nigral deep brain stimulation on speech and voice in Parkinson's patients.","authors":"Frank Müller, Julie Cläre Nienstedt, Carsten Buhmann, Ute Hidding, Alessandro Gulberti, Monika Pötter-Nerger, Christina Pflug","doi":"10.1007/s00702-024-02860-5","DOIUrl":"https://doi.org/10.1007/s00702-024-02860-5","url":null,"abstract":"<p><p>Deep brain stimulation can influence the speech and voice quality in Parkinson´s disease (PD). This controlled, randomized, double-blind, cross-over clinical trial was conducted in 15 PD patients with bilateral subthalamic deep brain stimulation (DBS) to compare the effects of STN-DBS with combined subthalamic and nigral stimulation (STN + SNr-DBS) and DBS OFF on speech and voice parameters in PD patients. Speech and voice were analyzed subjectively using questionnaires (voice/pronunciation quality VAS, VHI, SHI) and objectively using audio analysis (maximum phonation time, AVQI, mean F0, intonation, syllable rate, reading time). Both stimulation conditions, STN + SNr-DBS and STN-DBS, revealed heterogeneous effects on speech and voice production with a slight beneficial effect on the voice quality of individual patients compared to DBS OFF, but not in the whole group. Small, but not significant effects were seen only in subjective voice quality on the VAS and intonation (both stimulation conditions compared to DBS OFF). No significant changes of the objective speech parameters during the audio analysis could be observed (both stimulation conditions compared to DBS OFF). There were no significant differences between STN + SNr-DBS and STN-DBS in any speech and voice domain. The beneficial effects on speech and voice production are minor in most patients compared to the motor improvements by DBS. Both STN-DBS and STN + SNr-DBS were safe, with comparable effects between both DBS modes, and represent no contraindications from the perspective of the voice specialist.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739815","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 effectiveness of non-invasive brain stimulation in treatment of major depressive disorder (MDD): a systematic review and transfer analysis.","authors":"Vahid Nejati, Azin Sarraj Khorrami, Zahra S Vaziri, Fatemeh Shahri, Maryam Yazdchi, Vahid Abdolmanafi, Saeed Paydarfard, Aida Golshan","doi":"10.1007/s00702-024-02852-5","DOIUrl":"https://doi.org/10.1007/s00702-024-02852-5","url":null,"abstract":"<p><p>This study aimed to analyze the transferability of non-invasive brain stimulation (NIBS) interventions in individuals with major depressive disorder (MDD) based on the FIELD model (Function, Implementation, Ecology, Level, and Duration), encompassing function, implement, ecology, level, and duration. A systematic search of electronic databases yielded a total of 21 eligible studies, comprising 12 transcranial direct current stimulation (tDCS) and 9 transcranial magnetic stimulation (TMS) trials, involving 1029 individuals with MDD. The meta-analysis of effect sizes revealed positive transfer effects across all domains of the FIELD model, suggesting that NIBS interventions have potential efficacy in improving various facets of MDD. The subgroup analysis highlighted that bilateral dlPFC stimulation exhibited the highest effect size for transferability, indicating greater transferability for rTMS, a higher dose of stimulation, and the integration of additional interventions. Additionally, the study discusses the implications of bilateral dorsolateral prefrontal cortex (dlPFC) stimulation and the integration of complementary therapies for optimizing treatment efficacy.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710399","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":"Subtle bradykinesia features are easier to identify and more prevalent than questionable dystonia in essential tremor.","authors":"Giulia Paparella, Luca Angelini, Valentina Cannizzo, Simone Aloisio, Adriana Martini, Daniele Birreci, Davide Costa, Martina De Riggi, Antonio Cannavacciuolo, Matteo Bologna","doi":"10.1007/s00702-024-02861-4","DOIUrl":"https://doi.org/10.1007/s00702-024-02861-4","url":null,"abstract":"<p><p>Essential tremor (ET) is characterized by upper limbs action tremor, sometimes extending to other body parts. However, ET can present with additional neurological features known as \"soft signs.\" These signs of uncertain clinical significance are not sufficient to suggest an alternative neurological diagnosis, and include, among others, questionable dystonia and subtle voluntary movement alterations, i.e., bradykinesia and related features. This study aimed to explore the prevalence and relationship between questionable dystonia and subtle bradykinesia features in ET. Forty ET patients were video-recorded during clinical examination. Five movement disorder experts reviewed the videos to identify soft motor signs, i.e., dystonia and movement alterations during finger-tapping namely, (i) bradykinesia (reduced velocity), (ii) dysrhythmia, and (iii) sequence effect. Inter-rater agreement was quantified using the Fleiss' Kappa index. Data analysis was performed using nonparametric tests. We found a fair inter-rater agreement for upper limb dystonia (Fleiss' K = 0.27). Inter-rater agreement was higher (moderate) for head dystonia (Fleiss' K = 0.49) and finger-tapping assessment (Fleiss' K = 0.45). Upper limb dystonia was identified in 70% of patients, head dystonia in 35%, and finger-tapping alterations (in variable combinations) were observed in 95% of individuals (P < 0.001 by Fisher's exact test), including subtle bradykinesia and related features. No significant concordance or correlation was found between the soft signs. Subtle bradykinesia and related features are the most easily identifiable and frequent soft signs in ET, appearing in a higher percentage of patients than subtle dystonia. These findings provide insights into the clinical and pathophysiological understanding of ET.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682077","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":"An orthogonal approach for analysis of underivatized steroid hormones using ultrahigh performance supercritical fluid chromatography-mass spectrometry (UHPSFC-MS).","authors":"Perry Devo, Victoria Cretu, Harsha Radhakrishnan, Darren Hamilton-Pink, Stergios Boussios, Saak V Ovsepian","doi":"10.1007/s00702-024-02862-3","DOIUrl":"https://doi.org/10.1007/s00702-024-02862-3","url":null,"abstract":"<p><p>The crucial role of steroid hormones in health and diseases merits their high-throughput, accurate and affordable measurements in biological specimens. Despite advances in analytical methods, sensing and quantifying steroid hormones remains challenging. Immunoassays offer excellent sensitivity but are inherently labour-intensive, costly, and prone to false positives. Mass spectrometry (MS) has been increasingly utilised, with the main hurdle being the isobaric tendencies of similar analytes, which complicates their separation and accurate quantification. This study compares ultrahigh-performance supercritical fluid chromatography separation (UHPSFC) and ultra-high-performance liquid chromatography (UHPLC) for MS detection. It optimises the column chemistry, temperature, and pressure to provide an operational protocol for the resolution and quantification of analytes. It presents the systematic characterisation of UHPSFC-MS performance by investigating spiked blood samples using Solid-Phase Extraction (SPE) and describes the matrix effects associated with MS measurements. Although both separation methods showed adequate resolution, specificity, and retention time, UHPSFC-MS was superior for five out of seven columns tested. With added high-throughput capacities, UHPSFC-MS, thus, offers an optimal solution for the analysis of steroid hormones for research, medical chemistry, and clinical diagnostics.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639058","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":"https://doi.org/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":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}