Parkinsonism & related disorders最新文献

{"title":"Correlation between clinical and neuropathological subtypes of progressive supranuclear palsy","authors":"","doi":"10.1016/j.parkreldis.2024.106076","DOIUrl":"10.1016/j.parkreldis.2024.106076","url":null,"abstract":"<div><h3>Introduction</h3><div>Progressive supranuclear palsy (PSP) is characterized by pathology prominently in the basal ganglia, the tegmentum of the brainstem, and the frontal cortex. However, pathology varies according to clinical features. This study aimed to statistically verify the correspondence between the clinical and pathological subtypes of PSP.</div></div><div><h3>Methods</h3><div>We identified patients with a pathological diagnosis of PSP and classified the eight clinical subtypes of the Movement Disorders Society criteria for the clinical diagnosis of PSP (MDS-PSP criteria) into the Richardson, Akinesia, and Cognitive groups. We used anti-phosphorylated tau antibody immunostaining to semi-quantitatively evaluate neurofibrillary tangles (NFTs) and coiled bodies/threads (CB/Ths) in the globus pallidus, subthalamic nucleus, and midbrain tegmentum. In the frontal cortex, tufted astrocytes (TAs) and CB/Ths were assessed on a 3-point scale. We compared the pathology among the three groups, recorded the phenotypes ranked the second and lower in the multiple allocation extinction rule and examined whether the pathology changed depending on applying each phenotype.</div></div><div><h3>Results</h3><div>The Richardson group exhibited severe NFTs and CB/Ths in the midbrain tegmentum. The Akinesia group showed severe NFTs in the globus pallidus. The Cognitive group had severe TAs and CB/Ths in the frontal cortex. TAs and CB/Ths in the frontal cortex correspond to behavioral variant frontotemporal dementia, and supranuclear vertical oculomotor palsy.</div></div><div><h3>Conclusion</h3><div>These clinical symptoms may reflect the distribution of tau pathologies in PSP.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"127 ","pages":"Article 106076"},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140143998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic architecture of a single cohort of 230 Indian Parkinson's Disease patients","authors":"Sneha D. Kamath ,&nbsp;Prashant Phulpagar ,&nbsp;Vikram V. Holla ,&nbsp;Nitish Kamble ,&nbsp;Ravi Yadav ,&nbsp;Babylakshmi Muthusamy ,&nbsp;Pramod Kumar Pal","doi":"10.1016/j.parkreldis.2024.107157","DOIUrl":"10.1016/j.parkreldis.2024.107157","url":null,"abstract":"<div><h3>Introduction</h3><div>Indian Parkinson's Disease (PD) patients are severely underrepresented in terms of genetic studies and little is known about the frequency of variants and their impact on motor and nonmotor symptoms (NMS).</div></div><div><h3>Methods</h3><div>This retrospective cross-sectional study was conducted in PD patients undergoing treatment at a tertiary care hospital from India. Patients were advised genetic testing if they had (i) age at onset (AAO) of motor symptoms at or before 50 years (EOPD), (ii) positive family history of PD, parkinsonism or dystonia. All patients underwent whole exome sequencing and potentially pathogenic variants were identified.</div></div><div><h3>Results</h3><div>Clinical and genetic data were available for 230 (163 males, 70.4 %) patients. Thirty-five pathogenic and likely pathogenic variants in various PD genes were identified in 47 patients resulting in a yield of 20.4 %. In the remaining, 82 patients had either variants of uncertain significance or had variants in genes not associated with parkinsonism and 101 patients did not have any non-benign variants. Patients with genetically mediated PD had a lower AAO and statistically greater frequency of dystonia (36.2 %), postural instability (29.8 %) and mood disorder (29.8 %) and a higher Hoehn and Yahr score (2.9). Among the 47 patients, 11 patients had PARK-<em>PRKN</em>, six patients had PARK-<em>PLA2G6</em>, and 22 patients had PARK-<em>GBA1</em>.</div></div><div><h3>Conclusion</h3><div>Around one-fifth of early-onset PD can have an underlying monogenetic cause. PARK<em>-GBA1,</em> PARK<em>-PRKN</em> and PARK-<em>PLA2G6</em> are the commoner causes of genetically mediated PD in India. Patients with genetic cause had an earlier age at onset, and more frequent dystonia, postural instability and dyskinesia.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"129 ","pages":"Article 107157"},"PeriodicalIF":3.1,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Nicotine-Parkinson's disease link – Insights from the UK Biobank","authors":"Sarah Bouhadoun ,&nbsp;Sheida Zolfaghari ,&nbsp;Aline Delva ,&nbsp;Amélie Pelletier ,&nbsp;Trycia Kouchache ,&nbsp;Alain Dagher ,&nbsp;Filip Morys ,&nbsp;Andrew Vo ,&nbsp;Mirja Kuhlencord ,&nbsp;Ronald Postuma","doi":"10.1016/j.parkreldis.2024.107156","DOIUrl":"10.1016/j.parkreldis.2024.107156","url":null,"abstract":"<div><h3>Introduction</h3><div>Evidence suggests an inverse correlation between smoking and Parkinson's disease (PD), yet the mechanisms remain unclear. This study examines the changing risk relationship between smoking and PD diagnosis using alcohol consumption, another reward-driven behavior, as a comparative measure.</div></div><div><h3>Methods</h3><div>A nested case-control study was conducted using the UK Biobank (UKBB) database. Participants in the prediagnostic phase of PD were identified, and self-reported data on tobacco and alcohol use were analyzed employing conditional binary logistic regression. Polynomial and piece-wise regression models were employed to discern shifting associations with PD over time.</div></div><div><h3>Results</h3><div>Of 502,304 participants (63 ± 5.3 years, 63 % male), 3049 prediagnostic PD cases were identified. Non-smokers had a heightened PD risk, and this association strengthened closer to diagnosis. The odds ratio (OR [95 % CI]) associated with PD in non-smokers was 2.02 [1.07–3.81] 1–4 years before diagnosis, compared to 1.36 [1.02–1.83] at &gt;10-year intervals (linear trend, p = 0.012). The time trajectory of ORs was best depicted by a quadratic function, identifying a shift in risk 7.5 years before diagnosis documentation. Similar patterns emerged among alcohol non-consumers, with an 8.5-year interval inflection point.</div></div><div><h3>Conclusion</h3><div>This study identified two disparate risk trajectories among non-smokers: an initial low-amplitude increased risk at prolonged prediagnostic intervals possibly related to genetic/personality factors, followed by a sharp escalation in risk association commencing 7–8 years before diagnosis, possibly propelled by reverse causality. Similar trends in alcohol consumption reinforce these conclusions. These findings could suggest that smoking cessation may serve as an early indicator of PD.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"129 ","pages":"Article 107156"},"PeriodicalIF":3.1,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Magnetic resonance spectroscopy reveals evidence of brain oxidative stress in Tourette syndrome","authors":"Marianna Sarchioto,&nbsp;Franklyn Howe,&nbsp;Francesca Morgante,&nbsp;Jeremy Stern,&nbsp;Mark J. Edwards,&nbsp;Davide Martino","doi":"10.1016/j.parkreldis.2024.107154","DOIUrl":"10.1016/j.parkreldis.2024.107154","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"128 ","pages":"Article 107154"},"PeriodicalIF":3.1,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional efficacy of the MAO-B inhibitor safinamide in murine substantia nigra pars compacta dopaminergic neurons in vitro: A comparative study with tranylcypromine","authors":"Beatrice Zarrilli ,&nbsp;Cecilia Giacomet ,&nbsp;Francesca Cossa ,&nbsp;Mauro Federici ,&nbsp;Nicola Berretta ,&nbsp;Nicola B. Mercuri","doi":"10.1016/j.parkreldis.2024.107158","DOIUrl":"10.1016/j.parkreldis.2024.107158","url":null,"abstract":"<div><div>Safinamide (SAF) is currently used to treat Parkinson's disease (PD) symptoms based on its theoretical ability to potentiate the dopamine (DA) signal, blocking monoamine oxidase (MAO) B. The present work aims to highlight the functional relevance of SAF as an enhancer of the DA signal, by evaluating its ability to prolong recovery from DA-mediated firing inhibition of DAergic neurons of the substantia nigra pars compacta (SNpc), compared to another MAO antagonist, tranylcypromine (TCP). Using multielectrode array (MEA) and single electrode extracellular recordings of spontaneous spikes from presumed SNpc DAergic cells <em>in vitro</em>, we show that SAF (30 μM) mildly prolongs the DA-mediated firing inhibition, as opposed to the profound effect of TCP (10 μM). In patch-clamp recordings, we found that SAF (30 μM) significantly reduced the number of spikes evoked by depolarizing currents in SNpc DAergic neurons, in a sulpiride (1 μM) independent manner. According to our results, SAF marginally potentiates the DA signal in SNpc DAergic neurons, while exerting an inhibitory effect on the postsynaptic excitability acting on membrane conductances. Thus, we propose that the therapeutic effects of SAF in PD patients partially depends on MAO inhibition, while other MAO-independent sites of action could be more relevant.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"128 ","pages":"Article 107158"},"PeriodicalIF":3.1,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142319162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Supplemental ambient lighting intervention to improve sleep in Parkinson's disease: A pilot trial","authors":"Andrea S. Yoo ,&nbsp;Adina Wise ,&nbsp;Roberto A. Ortega ,&nbsp;Deborah Raymond ,&nbsp;Barbara Plitnick ,&nbsp;Jennifer Brons ,&nbsp;Judy Liang ,&nbsp;Susan B. Bressman ,&nbsp;Mengxi Yang ,&nbsp;David Pedler ,&nbsp;Mariana G. Figueiro ,&nbsp;Rachel Saunders-Pullman","doi":"10.1016/j.parkreldis.2024.107149","DOIUrl":"10.1016/j.parkreldis.2024.107149","url":null,"abstract":"<div><h3>Importance</h3><div>Sleep disturbances in Parkinson's disease (PD) are common and often adversely affect quality of life. Light therapy has benefited sleep quality and mood outcomes in various populations but results to date with conventional light therapy boxes in PD patients have been mixed. We hypothesized that a passive lighting intervention, applied in the morning and designed to maximally affect the circadian system, would improve measures of sleep and mood in PD patients.</div></div><div><h3>Methods</h3><div>In this single-arm, within-subjects intervention study, baseline objective sleep (actigraphy), subjective sleep quality (questionnaires), and subjective mood (questionnaires) data were collected for 1 week. Lighting was then administered to participants via table/floor lamps installed in the home or via personal light therapy glasses for 2 h in the morning, 7 days per week, over the following 4-week period. Post-intervention data for the same outcomes were collected during the final week of the intervention period.</div></div><div><h3>Results</h3><div>Among 20 participants (12 women, 8 men; mean [SD] age 72.1 [9.5] years, disease duration 9.0 [5.2] years), objective sleep duration increased significantly by 28.5 min (<em>p</em> = 0.029) and objective sleep time increased significantly by 19.9 min (<em>p</em> = 0.026).</div></div><div><h3>Conclusion</h3><div>Passive and easily administered lighting interventions for improving sleep in PD patients hold promise as a treatment for mitigating symptoms and improving quality of life in PD.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"129 ","pages":"Article 107149"},"PeriodicalIF":3.1,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142433170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anemia, blood cell indices, genetic correlations, and brain structures: A comprehensive analysis of roles in Parkinson's disease risk","authors":"Chun-yan Zuo ,&nbsp;Xiao-yan Hao ,&nbsp;Meng-jie Li ,&nbsp;Meng-nan Guo ,&nbsp;Dong-rui Ma ,&nbsp;Shuang-jie Li ,&nbsp;Yuan-yuan Liang ,&nbsp;Chen-Wei Hao ,&nbsp;Zhi-yun Wang ,&nbsp;Yan-Mei Feng ,&nbsp;Yue-meng Sun ,&nbsp;Yu-ming Xu ,&nbsp;Chang-he Shi","doi":"10.1016/j.parkreldis.2024.107153","DOIUrl":"10.1016/j.parkreldis.2024.107153","url":null,"abstract":"<div><h3>Introduction</h3><div>Anemia may contribute significantly to the onset of Parkinson's disease (PD). Current research on the association between anemia and PD risk is inconclusive, and the relationships between anemia-related blood cell indices and PD incidence require further clarification. This study aims to investigate the relationships between anemia, blood cell indicators, and PD risk using a thorough prospective cohort study.</div></div><div><h3>Methods</h3><div>We used data from the UK Biobank, a prospective cohort study of 502,649 participants, and ultimately, 365,982 participants were included in the analysis. Cox proportional hazards models were utilized to adjust for confounding factors, aiming to thoroughly explore the associations between anemia and blood cell indices with the risk of incident PD. The interaction between anemia and Polygenic Risk Score (PRS) for PD was also examined. Linear regression and mediation analyses assessed potential mechanisms driven by brain structures, including grey matter volume.</div></div><div><h3>Results</h3><div>During a median follow-up of 14.24 years, 2513 participants were diagnosed with PD. Anemia considerably increased PD risk (hazard ratio [HR] 1.98, 95 % confidence interval [CI]: 1.81–2.18, P &lt; 0.001) after adjustments. Those with high PRS for anemia had an 83 % higher PD incidence compared to low PRS participants. Sensitivity analyses confirmed result robustness. Linear regression showed that anemia correlated with grey matter volumes and most white matter tracts. Furthermore, mediation analyses identified that the volume of grey matter in Thalamus mediates the relationship between anemia and PD risk.</div></div><div><h3>Conclusion</h3><div>In summary, we consider there to be a substantial correlation between anemia and increased PD risk.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"128 ","pages":"Article 107153"},"PeriodicalIF":3.1,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142311264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Movement disorders in Megalencephalic Leukoencephalopathy with subcortical cysts – A case series","authors":"Jacky Ganguly ,&nbsp;Divyani Garg ,&nbsp;Mitesh Chandarana ,&nbsp;Purba Basu ,&nbsp;Neha Pandita ,&nbsp;Soumava Mukherjee ,&nbsp;Nilam Singh ,&nbsp;Anup Rawool ,&nbsp;Gourav Sannyasi ,&nbsp;Praveen Kumar ,&nbsp;Hrishikesh Kumar","doi":"10.1016/j.parkreldis.2024.107152","DOIUrl":"10.1016/j.parkreldis.2024.107152","url":null,"abstract":"<div><h3>Background</h3><div>Megalencephalic leukoencephalopathy with subcortical cysts (MLC) has been described in the literature mostly as early-onset leukodystrophy with cerebellar ataxia being the main clinical phenotype. However, other associated movement disorders have also been reported discretely.</div></div><div><h3>Cases</h3><div>Here, we present seven cases of MLC. Cerebellar ataxia was common in them, while dystonia was present in six, parkinsonism in one and stereotypy in two. Six of them, belonging to the Agarwal community, had the common c.135dup variant.</div></div><div><h3>Conclusion</h3><div>Our observation highlights the presence of movement disorders in MLC beyond cerebellar ataxia and phenotypic variability of the c.135dup variant, prevalent in the Agarwal community.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"128 ","pages":"Article 107152"},"PeriodicalIF":3.1,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142319163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognitive phenotyping of GBA1-Parkinson's disease: A study on deep brain stimulation outcomes","authors":"Joan Miquel Fernández-Vidal ,&nbsp;Ignacio Aracil-Bolaños ,&nbsp;Carmen García-Sánchez ,&nbsp;Antonia Campolongo ,&nbsp;Mireia Curell ,&nbsp;Rodrigo Rodríguez-Rodriguez ,&nbsp;Juan Ángel Aibar-Duran ,&nbsp;Jaime Kulisevsky ,&nbsp;Berta Pascual-Sedano","doi":"10.1016/j.parkreldis.2024.107127","DOIUrl":"10.1016/j.parkreldis.2024.107127","url":null,"abstract":"<div><h3>Background</h3><div>Heterozygous variants in the glucocerebrosidase (<em>GBA1</em>) gene are the most common genetic risk factor for Parkinson's Disease (PD). <em>GBA1</em>-PD patients exhibit earlier disease onset, severe motor impairment, and heightened cognitive decline. Deep Brain Stimulation (DBS) offers motor improvement for PD patients, but its cognitive effects, particularly in <em>GBA1</em>-PD, are debated.</div></div><div><h3>Methods</h3><div>This study involved 96 PD patients who underwent subthalamic nucleus DBS at Hospital de la Santa Creu i Sant Pau between 2004 and 2023. Clinical and neuropsychological assessments were conducted pre- and post-surgery, focusing on Mattis Dementia Rating Scale (MDRS) and Frontal Systems Behavior Scale (FrSBe). Patients were categorized into <em>GBA1</em>-PD and non-<em>GBA1</em>-PD groups, with non-<em>GBA1</em>-PD further divided into cognitive <em>fast-progressors</em> and <em>slow-progressors</em>.</div></div><div><h3>Results</h3><div><em>GBA1</em> variants were present in 13.5 % of patients. <em>GBA1</em>-PD patients showed greater cognitive decline over time, particularly in attention, conceptualization, and memory, compared to non-<em>GBA1</em>-PD. Non-<em>GBA1</em>-PD <em>fast-progressors</em> exhibited significant cognitive deterioration in initiation and conceptualization within the first year post-DBS. Motor outcomes improved similarly across all groups, but <em>slow-progressors</em> showed a greater reduction in Levodopa Equivalent Daily Dose (LEDD).</div></div><div><h3>Conclusions</h3><div><em>GBA1</em>-PD patients experience more rapid cognitive decline, particularly in posterior-cortical and fronto-striatal functions. Additionally, a subset of non-<em>GBA1</em>-PD patients shows significant early cognitive decline post-DBS, especially in executive functions. Baseline MDRS scores do not predict cognitive outcomes, highlighting the need for further research to refine prognostic tools. Despite cognitive challenges, <em>GBA1</em>-PD patients benefit from DBS in terms of motor outcomes, underscoring the importance of individualized assessments for DBS suitability, regardless of genetic status.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"128 ","pages":"Article 107127"},"PeriodicalIF":3.1,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142359651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of tremor-modulating effects of primidone and propranolol in essential tremor","authors":"Katarina Vogelnik Žakelj ,&nbsp;Neža Prezelj ,&nbsp;Milica Gregorič Kramberger ,&nbsp;Maja Kojović","doi":"10.1016/j.parkreldis.2024.107151","DOIUrl":"10.1016/j.parkreldis.2024.107151","url":null,"abstract":"<div><h3>Introduction</h3><div>Primidone and propranolol are primary treatments for essential tremor, however the exact mechanisms underlying their efficacy are not fully elucidated. Understanding how these medications alleviate tremor may guide the development of additional pharmacologic treatments. Our prospective observational study employed transcranial magnetic stimulation (TMS) to explore mechanisms of primidone and propranolol effects in essential tremor. Eyeblink classical conditioning (EBCC) was tested as a potential predictor of treatment response.</div></div><div><h3>Methods</h3><div>Patients with essential tremor underwent two evaluations: prior to commencing primidone or propranolol and following a minimum of three months of treatment. Tremor severity was assessed using accelerometry and clinically. TMS was employed to study changes in corticospinal excitability - resting and active motor thresholds, resting and active input/output curves and intracortical excitability - cortical silent period (CSP), short interval intracortical inhibition intensity curve (SICI), long interval intracortical inhibition (LICI), intracortical facilitation (ICF), and short afferent inhibition (SAI). EBCC, a marker of cerebellar function, was studied at baseline.</div></div><div><h3>Results</h3><div>Of the 54 enrolled patients (28 primidone, 26 propranolol), 35 completed both visits. Primidone effect on decreasing hand tremor was associated with decreased corticospinal excitability, prolongation of CSP, increased LICI, increased SAI and decreased SICI. Propranolol effect on hand tremor was associated with decreased corticospinal excitability and increased SAI. Better EBCC at baseline predicted better response to primidone.</div></div><div><h3>Conclusions</h3><div>Primidone exerts its therapeutic effects by blocking voltage-gated sodium channels and by modulating GABA-A and GABA-B intracortical circuits. Propranolol's central effects are likely mediated via noradrenergic modulation of GABA outflow.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"128 ","pages":"Article 107151"},"PeriodicalIF":3.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1353802024011635/pdfft?md5=7a924fd04f5bacba5de19fc6195c5673&pid=1-s2.0-S1353802024011635-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142316149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}