Journal of Neural Transmission最新文献

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Non-motor symptoms of Parkinson`s disease-insights from genetics 帕金森病的非运动症状--遗传学的启示
IF 3.3 4区 医学
Journal of Neural Transmission Pub Date : 2024-09-19 DOI: 10.1007/s00702-024-02833-8
Kristina Gotovac Jerčić, Antonela Blažeković, Sabina Borovečki, Fran Borovečki
{"title":"Non-motor symptoms of Parkinson`s disease-insights from genetics","authors":"Kristina Gotovac Jerčić, Antonela Blažeković, Sabina Borovečki, Fran Borovečki","doi":"10.1007/s00702-024-02833-8","DOIUrl":"https://doi.org/10.1007/s00702-024-02833-8","url":null,"abstract":"<p>Parkinson’s disease (PD) is a neurodegenerative disorder characterized by both motor and non-motor symptoms (NMS). NMS including sleep disturbances, depression, anxiety, and constipation are diverse, can precede motor symptoms, and significantly impact patients` quality of life. The severity and type of NMS vary based on age, disease severity, and motor symptoms, and while some respond to dopaminergic treatments, others may be induced or exacerbated by such treatments. NMS also play a role in differentiating PD from drug-induced parkinsonism and are related to gait dysfunction in both early and advanced stages. Genetic factors play a significant role in the development of NMS in PD, with mutations in genes such as SNCA, LRRK2, PRKN, and GBA being associated with severe and early NMS. Familial studies and identification of susceptibility factors have provided insights into the genetic underpinnings of NMS in PD. Neurobehavioral changes, including cognitive decline, are common NMS in PD, and their genetic basis involves a spectrum of mutations shared with other neurodegenerative disorders. Further research is needed to elucidate the functional implications of these genetic factors and their contributions to the pathogenesis of NMS in PD.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142263873","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}
引用次数: 0
Understanding clinical meaningfulness when targeting the depressor anguli oris muscle (DAO) with neuromodulators: a clinical prospective interventional study 了解神经调节剂针对口角下压肌(DAO)的临床意义:一项临床前瞻性干预研究
IF 3.3 4区 医学
Journal of Neural Transmission Pub Date : 2024-09-14 DOI: 10.1007/s00702-024-02835-6
Victor R. M. Munoz-Lora, Vanessa Thiesen, Dannyelle Loureiro, Gabriela Giro, Michael Alfertshofer, Sebastian Cotofana, Marcelo Germani
{"title":"Understanding clinical meaningfulness when targeting the depressor anguli oris muscle (DAO) with neuromodulators: a clinical prospective interventional study","authors":"Victor R. M. Munoz-Lora, Vanessa Thiesen, Dannyelle Loureiro, Gabriela Giro, Michael Alfertshofer, Sebastian Cotofana, Marcelo Germani","doi":"10.1007/s00702-024-02835-6","DOIUrl":"https://doi.org/10.1007/s00702-024-02835-6","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Neuromodulator injections in the US increased by 24% from 2021 to 2022. This rise is attributed to new products and growing acceptance of minimally invasive aesthetic treatments. Recent studies emphasize the importance of facial anatomy for precision and, consequently, a higher efficacy of neuromodulator treatments. This study aims to evaluate the clinical efficacy of a novel previously proposed injection technique targeting the depressor anguli oris (DAO) muscle to improve oral commissure position. This clinical, prospective study included 34 volunteers from the Shinobu Clinic, São Paulo, Brazil. Patients received 3 units of onabotulinumtoxinA per side, injected mid-distance between the oral commissure and jawline, following the labiomandibular sulcus (LMS). Standardized photographs and assessments using the Oral Commissure Severity Scale (OCSS) and Global Aesthetic Improvement Scale (GAIS) were conducted before and 30 days post-treatment. Statistical analyses included t-tests, Wilcoxon Signed Rank test, and generalized linear models. The average increase in commissural height was 5.22% (p &lt; 0.001). OCSS ratings improved significantly from baseline (clinician: 1.21 to 0.72, p &lt; 0.001; patient: 0.93 to 0.69, p &lt; 0.001). However, GAIS scores indicated no significant change (patient: 0.32, observer: 0.38; p = 0.491). The proposed injection technique improves perioral aesthetics objectively and subjectively. However, the lack of significant change in GAIS scores suggests that perceived improvements may not be clinically meaningful to patients. Future studies should focus on patient-centered evaluation methods to better assess aesthetic outcomes.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142263874","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}
引用次数: 0
Dopamine agonists in the treatment of Parkinson's disease: the show must go on 治疗帕金森病的多巴胺受体激动剂:演出必须继续
IF 3.3 4区 医学
Journal of Neural Transmission Pub Date : 2024-09-11 DOI: 10.1007/s00702-024-02825-8
Wolfgang H. Jost
{"title":"Dopamine agonists in the treatment of Parkinson's disease: the show must go on","authors":"Wolfgang H. Jost","doi":"10.1007/s00702-024-02825-8","DOIUrl":"https://doi.org/10.1007/s00702-024-02825-8","url":null,"abstract":"<p>Dopamine agonists (DA) have proven very successful in the treatment of Parkinson’s disease for a good many years now. In the 1990’s they experienced a high level of acceptance particularly in the European countries because their efficacy was in fact established, their tolerability was improved on and, in addition, several preparations were available with longer effect durations. But the discovery of cardiac fibroses led to a substantial setback and even rejection of therapy using ergoline DA. In recent years, impulse control disturbances have been observed increasingly with the result that higher doses have been reduced and the previously popular use of non-ergoline DA was discontinued. In addition, newer data on levodopa were published which clearly relativized the occurrence of late complications under levodopa and led to a differentiated use. Thus the importance of their use has waned over the years. But we should rather avoid repeating the mistakes of the past. DA serve us well and reliably so. The pendulum apparently thrives of the extremes but in the case of DA we should keep from falling back into the other extreme: We can and in fact must further make use of the DA, but with a clear view of specific goals and in a differentiated way. DA constitute the second-most important substance class after levodopa. Their optimized application can only be recommended for the good of our patients.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142192719","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}
引用次数: 0
Autonomic regulation and comorbid symptoms in children with attention deficit hyperactivity disorder 注意缺陷多动障碍儿童的自主神经调节和合并症状
IF 3.3 4区 医学
Journal of Neural Transmission Pub Date : 2024-09-11 DOI: 10.1007/s00702-024-02832-9
Kira Kehm, Susan Schloß, Christopher Mann, Katja Becker, Udo König, Wilfried Pott, Mira-Lynn Chavanon, Ursula Pauli-Pott
{"title":"Autonomic regulation and comorbid symptoms in children with attention deficit hyperactivity disorder","authors":"Kira Kehm, Susan Schloß, Christopher Mann, Katja Becker, Udo König, Wilfried Pott, Mira-Lynn Chavanon, Ursula Pauli-Pott","doi":"10.1007/s00702-024-02832-9","DOIUrl":"https://doi.org/10.1007/s00702-024-02832-9","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Objective</h3><p>Vagally-mediated heart rate variability (vmHRV) is regarded as transdiagnostic marker of emotion regulation and cognitive control capacity. We analysed vmHRV of children with attention deficit/hyperactivity disorder (ADHD). Based on previous research, we expected to find comorbid symptom dimensions (i.e. internalizing symptoms, conduct problems (CP), and callous unemotional (CU) traits) to relate to vmHRV measures.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>The sample comprised 100 (70 boys) medication naïve children with ADHD. Children were 6 to 11 years old. High frequency HRV (HF-HRV) was measured at rest and during a delay of gratification task. Additionally, sympathetic reactivity was assessed via skin conductance responses (SCR). Comorbid symptoms were assessed by parent-report questionnaires and clinical interviews.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The multiple correlation between CU traits and the HF-HRV scores proved statistically significant. Higher CU traits were associated with higher HRV resting-state and response scores. CP were positively associated with the SCR score.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>In children with ADHD, increased CU traits might point to a comparatively less impaired self-regulation capacity in the reward-related context. The result corresponds to findings from previous studies. In the future, CU traits should be considered in analyses of autonomic regulation in ADHD.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142192720","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}
引用次数: 0
An efficient ranking-based ensembled multiclassifier for neurodegenerative diseases classification using deep learning. 利用深度学习为神经退行性疾病分类提供高效的基于排序的集合多分类器。
IF 3.2 4区 医学
Journal of Neural Transmission Pub Date : 2024-09-09 DOI: 10.1007/s00702-024-02830-x
Palak Goyal, Rinkle Rani, Karamjeet Singh
{"title":"An efficient ranking-based ensembled multiclassifier for neurodegenerative diseases classification using deep learning.","authors":"Palak Goyal, Rinkle Rani, Karamjeet Singh","doi":"10.1007/s00702-024-02830-x","DOIUrl":"https://doi.org/10.1007/s00702-024-02830-x","url":null,"abstract":"<p><p>Neurodegenerative diseases are group of debilitating and progressive disorders that primarily affect the structure and functions of nervous system, leading to gradual loss of neurons and subsequent decline in cognitive, and behavioral activities. The two frequent diseases affecting the world's significant population falling in the above category are Alzheimer's disease (AD) and Parkinson's disease (PD). These disorders substantially impact the quality of life and burden healthcare systems and society. The demographic characteristics, and machine learning approaches have now been employed to diagnose these illnesses; however, they possess accuracy limitations. Therefore, the authors have developed ranking-based ensemble approach based on the weighted strategy of deep learning classifiers. The whole modeling procedure of the proposed approach incorporates three phases. In phase I, preprocessing techniques are applied to clean the noise in datasets to make it standardized according to deep learning models as it significantly impacts their performance. In phase II, five deep learning models are selected for classification and calculation of prediction results. In phase III, a ranking-based ensemble approach is proposed to ensemble the results of the five models after calculating the ranks and weights of them. In addition, the Magnetic Resonance Imaging (MRI) datasets named Alzheimer's Disease Neuroimaging Initiative (ADNI) for AD classification and Parkinson's Progressive Marker Initiative (PPMI) for PD classification are selected to validate the proposed approach. Furthermore, the proposed method achieved the classification accuracy on AD- Cognitive Normals (CN) at 97.89%, AD- Mild Cognitive Impairment (MCI) at 99.33% and CN-MCI at 99.44% and on PD-CN at 99.22%, PD- Scans Without Evidence of Dopaminergic Effect (SWEDD) at 97.56% and CN-SWEDD at 98.22% respectively. Also, the multi-class classification shows the promising accuracy of 97.18% for AD and 97.85% for PD for the proposed framework. The findings of the study show that the proposed deep learning-based ensemble technique is competitive for AD and PD prediction in both multiclass and binary class classification. Furthermore, the proposed approach enhances generalization performance in diagnosing neurodegenerative diseases and performs better than existing approaches.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154429","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}
引用次数: 0
The relationship between sphingomyelin and ceramide levels and soft neurological signs in ADHD. 多动症患者的鞘磷脂和神经酰胺水平与软神经体征之间的关系。
IF 3.2 4区 医学
Journal of Neural Transmission Pub Date : 2024-09-09 DOI: 10.1007/s00702-024-02831-w
Ahmet Güleç, Serhat Türkoğlu, Ramazan Kocabaş
{"title":"The relationship between sphingomyelin and ceramide levels and soft neurological signs in ADHD.","authors":"Ahmet Güleç, Serhat Türkoğlu, Ramazan Kocabaş","doi":"10.1007/s00702-024-02831-w","DOIUrl":"https://doi.org/10.1007/s00702-024-02831-w","url":null,"abstract":"<p><p>Attention deficit hyperactivity disorder (ADHD), characterized by attention deficit, hyperactivity, and impulsivity, has recently been associated with lipid metabolism. In particular, the roles of sphingomyelin, ceramide, andgalactosylceramidase in the pathophysiology of ADHD are being investigated. This study aims to explore the relationship between sphingolipid metabolism markers and soft neurological signs (SNS) in children diagnosed with ADHD who are not undergoing medication treatment. A cross-sectional analysis was conducted on 41 children and adolescents aged 7-12 years diagnosed with ADHD and 39 neurotypically developing controls. Plasma levels of ceramide, sphingomyelin, and galactosylceramidase were measuredusing Enzyme-Linked Immunosorbent Assay (ELISA). SNS were assessed using the Physical and Neurological Examination for Soft Signs (PANESS). Statistical analyses included Student's t-tests, Mann-Whitney U tests, and Multivariate Analysis ofCovariance (MANCOVA), along with logistic regression analysis. Plasma levels of ceramide and sphingomyelin in children with ADHD showed significant differences compared to the neurotypically developing control group; however, there were no significant differences in galactosylceramidase levels between the two groups. Positive correlations were found between plasma levels of ceramide and sphingomyelin and the PANESS subscales F1 (Total Gait and Station) and F3 (Total Dysrhythmia). Additionally, logistic regression analysis indicated that high ceramide levels were positively associated with ADHD. This study underscores a significant association between alterations in sphingolipid metabolism (specifically increased levels of ceramide and sphingomyelin) and the presence of SNS in children with ADHD. These findings elucidate the potential role of sphingolipid metabolism in the pathophysiology of ADHD and provide suggestions for future therapeutic research targeting sphingolipid metabolism in the treatment of ADHD.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154430","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}
引用次数: 0
Behavioral disorders in dementia with Lewy bodies: old and new knowledge. 路易体痴呆症的行为障碍:新旧知识。
IF 3.2 4区 医学
Journal of Neural Transmission Pub Date : 2024-09-06 DOI: 10.1007/s00702-024-02823-w
Kurt A Jellinger
{"title":"Behavioral disorders in dementia with Lewy bodies: old and new knowledge.","authors":"Kurt A Jellinger","doi":"10.1007/s00702-024-02823-w","DOIUrl":"https://doi.org/10.1007/s00702-024-02823-w","url":null,"abstract":"<p><p>Dementia with Lewy bodies (DLB), the second most common primary degenerative neurocognitive disorder after Alzheimer disease, is frequently preceded by REM sleep behavior disorders (RBD) and other behavioral symptoms, like anxiety, irritability, agitation or apathy, as well as visual hallucinations and delusions, most of which occurring in 40-60% of DLB patients. Other frequent behavioral symptoms like attention deficits contribute to cognitive impairment, while attention-deficit/hyperactivity disorder (ADHD) is a risk factor for DLB. Behavioral problems in DLB are more frequent, more severe and appear earlier than in other neurodegenerative diseases and, together with other neuropsychiatric symptoms, contribute to impairment of quality of life of the patients, but their pathophysiology is poorly understood. Neuroimaging studies displayed deficits in cholinergic brainstem nuclei and decreased metabolism in frontal, superior parietal regions, cingulate gyrus and amygdala in DLB. Early RBD in autopsy-confirmed DLB is associated with lower Braak neuritic stages, whereas those without RBD has greater atrophy of hippocampus and increased tau burden. αSyn pathology in the amygdala, a central region in the fear circuitry, may contribute to the high prevalence of anxiety, while in attention dysfunctions the default mode and dorsal attention networks displayed diverging activity. These changes suggest that behavioral disorders in DLB are associated with marked impairment in large-scale brain structures and functional connectivity network disruptions. However, many pathobiological mechanisms involved in the development of behavioral disorders in DLB await further elucidation in order to allow an early diagnosis and adequate treatment to prevent progression of these debilitating disorders.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140360","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}
引用次数: 0
Unraveling the mechanisms of high-level gait control in functional gait disorders. 揭示功能性步态障碍的高级步态控制机制。
IF 3.2 4区 医学
Journal of Neural Transmission Pub Date : 2024-09-06 DOI: 10.1007/s00702-024-02829-4
Angela Sandri, Chiara Bonetto, Mirta Fiorio, Francesca Salaorni, Giulia Bonardi, Christian Geroin, Nicola Smania, Michele Tinazzi, Marialuisa Gandolfi
{"title":"Unraveling the mechanisms of high-level gait control in functional gait disorders.","authors":"Angela Sandri, Chiara Bonetto, Mirta Fiorio, Francesca Salaorni, Giulia Bonardi, Christian Geroin, Nicola Smania, Michele Tinazzi, Marialuisa Gandolfi","doi":"10.1007/s00702-024-02829-4","DOIUrl":"https://doi.org/10.1007/s00702-024-02829-4","url":null,"abstract":"<p><p>Functional gait disorders (FGDs) are a disabling subset of Functional Neurological Disorders in which presenting symptoms arise from altered high-level motor control. The dual-task paradigm can be used to investigate mechanisms of high-level gait control. The study aimed to determine the objective measures of gait that best discriminate between individuals with FGDs and healthy controls and the relationship with disease severity and duration. High-level spatiotemporal gait outcomes were analyzed in 87 patients with FGDs (79.3% women, average age 41.9±14.7 years) and 48 healthy controls (60.4% women, average age 41.9±15.7 years) on single and motor, cognitive, and visual-fixation dual tasks. The area under the curve (AUC) from the receiver operator characteristic plot and the dual-task effect (DTE) were calculated for each measure. Dual-task interference on the top single-task gait characteristics was determined by two-way repeated measures ANOVA. Stride time variability and its standard deviation (SD) failed to discriminate between the two groups in single and dual-task conditions (AUC<0.80 for all). Significant group x task interactions were observed for swing time SD and stride time on the cognitive dual tasks (p<0.035 for all). Longer disease duration was associated with poor gait performance and unsteadiness in motor and cognitive DTE (p<0.003) but improvement in stride length and swing time on the visual dual tasks (p<0.041). Our preliminary findings shed light on measures of gait automaticity as a diagnostic and prognostic gait biomarker and underline the importance of early diagnosis and management in individuals with FGDs.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140361","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}
引用次数: 0
Behavioral disorders in multiple sclerosis: a comprehensive review. 多发性硬化症的行为障碍:全面回顾。
IF 3.2 4区 医学
Journal of Neural Transmission Pub Date : 2024-09-04 DOI: 10.1007/s00702-024-02816-9
Kurt A Jellinger
{"title":"Behavioral disorders in multiple sclerosis: a comprehensive review.","authors":"Kurt A Jellinger","doi":"10.1007/s00702-024-02816-9","DOIUrl":"https://doi.org/10.1007/s00702-024-02816-9","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a heterogenous autoimmune-mediated disease of the central nervous system (CNS) characterized by inflammation, demyelination and chronic progressive neurodegeneration. Among its broad and unpredictable range of neuropsychiatric symptoms, behavioral changes are common, even from the early stages of the disease, while they are associated with cognitive deficits in advanced MS. According to DSM-5, behavioral disorders include attention deficits, oppositional, defiant and conduct disorders, anxiety, panic, obsessive-compulsive disorders (OCD), disruptive and emotional disorders, while others include also irritability, agitation, aggression and executive dysfunctions. Approximately 30 to 80% of individuals with MS demonstrate behavioral changes associated with disease progression. They are often combined with depression and other neuropsychiatric disorders, but usually not correlated with motor deficits, suggesting different pathomechanisms. These and other alterations contribute to disability in MS. While no specific neuropathological data for behavioral changes in MS are available, those in demyelination animal models share similarities with white matter and neuroinflammatory abnormalities in humans. Neuroimaging revealed prefrontal cortical atrophy, interhemispheric inhibition and disruption of fronto-striato-thalamic and frontoparietal networks. This indicates multi-regional patterns of cerebral disturbances within the MS pathology although their pathogenic mechanisms await further elucidation. Benefits of social, psychological, behavioral interventions and exercise were reported. Based on systematical analysis of PubMed, Google Scholar and Cochrane library, current epidemiological, clinical, neuroimaging and pathogenetic evidence are reviewed that may aid early identification of behavioral symptoms in MS, and promote new therapeutic targets and strategies.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132990","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}
引用次数: 0
Therapeutic drug monitoring in Parkinson's disease. 帕金森病的治疗药物监测。
IF 3.2 4区 医学
Journal of Neural Transmission Pub Date : 2024-09-03 DOI: 10.1007/s00702-024-02828-5
Thomas Müller, Manfred Gerlach, Gudrun Hefner, Christoph Hiemke, Wolfgang H Jost, Peter Riederer
{"title":"Therapeutic drug monitoring in Parkinson's disease.","authors":"Thomas Müller, Manfred Gerlach, Gudrun Hefner, Christoph Hiemke, Wolfgang H Jost, Peter Riederer","doi":"10.1007/s00702-024-02828-5","DOIUrl":"https://doi.org/10.1007/s00702-024-02828-5","url":null,"abstract":"<p><p>A patient-tailored therapy of the heterogeneous, neuropsychiatric disorder of Parkinson's disease (PD) aims to improve dopamine sensitive motor symptoms and associated non-motor features. A repeated, individual adaptation of dopamine substituting compounds is required throughout the disease course due to the progress of neurodegeneration. Therapeutic drug monitoring of dopamine substituting drugs may be an essential tool to optimize drug applications. We suggest plasma determination of levodopa as an initial step. The complex pharmacology of levodopa is influenced by its short elimination half-life and the gastric emptying velocity. Both considerably contribute to the observed variability of plasma concentrations of levodopa and its metabolite 3-O-methyldopa. These amino acids compete with other aromatic amino acids as well as branched chain amino acids on the limited transport capacity in the gastrointestinal tract and the blood brain barrier. However, not much is known about plasma concentrations of levodopa and other drugs/drug combinations in PD. Some examples may illustrate this lack of knowledge: Levodopa measurements may allow further insights in the phenomenon of inappropriate levodopa response. They may result from missing compliance, interactions e.g. with treatments for other mainly age-related disorders, like hypertension, diabetes, hyperlipidaemia, rheumatism or by patients themselves independently taken herbal medicines. Indeed, uncontrolled combination of compounds for accompanying disorders as given above with PD drugs might increase the risk of side effects. Determination of other drugs used to treat PD in plasma such as dopamine receptor agonists, amantadine and inhibitors of catechol-O-methyltransferase or monoamine oxidase B may refine and improve the value of calculations of levodopa equivalents. How COMT-Is change levodopa plasma concentrations? How other dopaminergic and non-dopaminergic drugs influence levodopa levels? Also, delivery of drugs as well as single and repeated dosing and continuous levodopa administrations with a possible accumulation of levodopa, pharmacokinetic behaviour of generic and branded compounds appear to have a marked influence on efficacy of drug treatment and side effect profile. Their increase over time may reflect progression of PD to a certain degree. Therapeutic drug monitoring in PD is considered to improve the therapeutic efficacy in the course of this devastating neurologic disorder and therefore is able to contribute to the patients' precision medicine. State-of-the-art clinical studies are urgently needed to demonstrate the usefulness of TDM for optimizing the treatment of PD.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126034","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}
引用次数: 0
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