Movement Disorders最新文献

{"title":"Neutrophil-Rich Infusion Site Reactions After Continuous Subcutaneous Application of Foslevodopa/Foscarbidopa","authors":"David Weise MD, Sebastian Haferkamp MD, PhD","doi":"10.1002/mds.30121","DOIUrl":"10.1002/mds.30121","url":null,"abstract":"<p>We read with great interest the article by Yoshihara et al.,<span><sup>1</sup></span> which provides insight into histopathologic features of cutaneous side effects caused by continuous subcutaneous injection of foslevodopa/foscarbidopa. Using a similar approach, we analyzed skin biopsies from two female patients with Parkinson's disease (PD) who developed an inflammatory injection site reaction 11 and 13 weeks, respectively, after initiating subcutaneous treatment with foslevodopa/foscarbidopa. Notably, our histopathologic findings differ from those reported by Yoshihara et al., revealing a neutrophil-rich inflammatory infiltrate.</p><p>Akinetic-rigid type, disease duration 24 years, Hoen and Yahr scale (H&Y) 4 ON, 5 OFF with severe motor fluctuations and dyskinesia, optic hallucinations and PD dementia, previously treated with continuous subcutaneous apomorphine for 3 years, immediate change to foslevodopa/foscarbidopa due to not well-controlled motor fluctuations and increasing optic hallucinations and delusion. Good improvement of motor fluctuations and dyskinesia. After 13 weeks of treatment (foslevodopa total dose 2592 mg, day rate 0.50 mL/hr, night rate 0.35 mL/hr, cannula change frequency [initially] 3 days) an oval, tender, poorly demarked, dome-shaped, erythematous swelling was noted around the infusion site (Fig. 1A,B). Patient denied itching or pain.</p><p>Akinetic-rigid type, disease duration 15 years, H&Y 3 ON, 5 OFF with severe motor fluctuations and severe dyskinesia, previously treated with continuous subcutaneous apomorphine for 6 months (cessation due to insufficient improvement of fluctuations and persistent nausea), start of foslevodopa/foscarbidopa 8 months later with very good improvement of motor fluctuations and dyskinesia. She developed a painless, oval, poorly demarked, erythematous plaque measuring 5 cm in diameter after 11 weeks of treatment (foslevodopa total dose 2861 mg, day rate 0.52 mL/hr, night rate 0.45 mL/hr, cannula change frequency 2 days, relevant concomitant medication with opicapone 50 mg 1×/day).</p><p>Histopathologic examination of both cases revealed a patchy inflammatory infiltrate in the deep dermis extending into the subcutaneous tissue, composed primarily of neutrophils mixed with lymphocytes and a few eosinophils (Fig. 1C,D). In contrast to our findings, Yoshihara et al. described the adverse skin reactions as lymphocyte-dominant inflammatory infiltrates in the adipose tissue. Interestingly, an eosinophil-rich panniculitis has been observed in response to subcutaneously administered apomorphine,<span><sup>2</sup></span> suggesting that the cellular components of immune responses to subcutaneous drug application may vary significantly. This notion is supported by the fact that a broad clinical spectrum of cutaneous side effects, including erythema, edema, cellulitis, panniculitis, subcutaneous nodule formation, and abscess formation, has been reported for both subcutaneous treatment regi","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"40 2","pages":"389-390"},"PeriodicalIF":7.4,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mds.30121","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TDP‐43 Cryptic RNAs in Perry Syndrome: Differences across Brain Regions and TDP‐43 Proteinopathies","authors":"Sarah R. Pickles, Jesus Gonzalez Bejarano, Anand Narayan, Lillian Daughrity, Candela Maroto Cidfuentes, Madison M. Reeves, Mei Yue, Paula Castellanos Otero, Virginia Estades Ayuso, Judy Dunmore, Yuping Song, Jimei Tong, Michael DeTure, Bailey Rawlinson, Monica Castanedes‐Casey, Jaroslaw Dulski, Catalina Cerquera‐Cleves, Yongjie Zhang, Keith A. Josephs, Dennis W. Dickson, Leonard Petrucelli, Zbigniew K. Wszolek, Mercedes Prudencio","doi":"10.1002/mds.30104","DOIUrl":"https://doi.org/10.1002/mds.30104","url":null,"abstract":"BackgroundPerry syndrome (PS) is a rare and fatal hereditary autosomal dominant neurodegenerative disorder caused by mutations in dynactin (<jats:italic>DCTN1</jats:italic>). PS brains accumulate inclusions positive for ubiquitin, transactive‐response DNA‐binding protein of 43 kDa (TDP‐43), and to a lesser extent dynactin.ObjectivesLittle is known regarding the contributions of TDP‐43, an RNA binding protein that represses cryptic exon inclusion, in PS. Therefore, we sought to identify the degree of TDP‐43 dysfunction in two regions of PS brains.MethodsWe evaluated the levels of insoluble pTDP‐43 and TDP‐43‐regulated cryptic RNAs and protein in the caudate nucleus and substantia nigra of 7 PS cases, 12 cases of frontotemporal lobar degeneration (FTLD) with TDP‐43 pathology, and 11 cognitively healthy controls without TDP‐43 pathology.ResultsInsoluble pTDP‐43 protein levels were detected in PS brains to a similar extent in the caudate nucleus and substantia nigra but lower than those in FTLD brains. The caudate nucleus of PS showed accumulation of eight TDP‐43‐regulated cryptic RNAs (<jats:italic>ACTL6B</jats:italic>, <jats:italic>CAMK2B</jats:italic>, <jats:italic>STMN2</jats:italic>, <jats:italic>UNC13A</jats:italic>, <jats:italic>KCNQ2</jats:italic>, <jats:italic>ATG4B</jats:italic>, <jats:italic>GPSM2</jats:italic>, and <jats:italic>HDGFL2</jats:italic>) and cryptic protein (HDGFL2) characteristic of FTLD. Conversely, only one cryptic target, <jats:italic>UNC13A</jats:italic>, reached significance in the substantia nigra despite similar pTDP‐43 levels.ConclusionWe detected TDP‐43 cryptic RNAs and protein in PS caudate nucleus. Given the importance of cryptic exon biology in the development of biomarkers, and the identification of novel targets for therapeutic intervention, it is imperative we understand the consequences of TDP‐43 dysfunction across different brain regions and determine the targets that are specific and common to TDP‐43 proteinopathies. © 2025 The Author(s). <jats:italic>Movement Disorders</jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"1 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142940146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of a Wrist Harmonic Liquid Tremor Absorber-Damping on the Upper Extremity Essential Tremor","authors":"Sultan Tarlacı MD,&nbsp;Furkan Doğan","doi":"10.1002/mds.30102","DOIUrl":"10.1002/mds.30102","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Essential tremor (ET) is a common type of tremor. Previous research has shown that wearable orthoses and biomechanical loading methods can suppress tremors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aims to investigate the effect of a harmonic liquid dampener on upper extremity ET.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The study involved 9 women and 5 men from a neurology outpatient clinic. A 285-g liquid-based harmonic dampening wristband was used. Tremors were recorded from the wrist along the <i>x</i>-<i>y</i>-<i>z</i> axes using a vibrometer, and the Bain–Findley Rating Scale (BFRS) was employed for assessment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>BFRS scores significantly improved after the wristband was used (mean difference 35.64, <i>P</i> = 0.001, Cohen's d effect size =2.979). The tremor amplitude decreased significantly along the <i>x</i>-axis (Cohen's d: 1.35, <i>P</i> = 0.001), <i>y</i>-axis (Cohen's d: 3.232, <i>P</i> = 0.001), and <i>z</i>-axis (Cohen's d: 3.321, <i>P</i> = 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The liquid-filled harmonic dampening wristband shows promise as a new, effective treatment option for ET patients. © 2025 International Parkinson and Movement Disorder Society.</p>\u0000 </section>\u0000 </div>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"40 3","pages":"537-543"},"PeriodicalIF":7.4,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prospective Multicenter Evaluation of the MDS “Suggestive of PSP” Diagnostic Criteria","authors":"Andrea Quattrone MD,&nbsp;Nicolai Franzmeier PhD,&nbsp;Johannes Levin MD,&nbsp;Gabor C. Petzold MD,&nbsp;Annika Spottke MD,&nbsp;Frederic Brosseron PhD,&nbsp;Björn Falkenburger MD,&nbsp;Johannes Prudlo MD,&nbsp;Thomas Gasser MD,&nbsp;The DESCRIBE-PSP Group, The ProPSP Group,&nbsp;Günter U. Höglinger MD","doi":"10.1002/mds.30112","DOIUrl":"10.1002/mds.30112","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The recent Movement Disorders Society (MDS)-progressive supranuclear palsy (PSP) diagnostic criteria conceptualized three clinical diagnostic certainty levels: “suggestive of PSP” for sensitive early diagnosis based on subtle clinical signs, “possible PSP” balancing sensitivity and specificity, and “probable PSP” highly specific for PSP pathology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The aim of this study was to prospectively validate the criteria against long-term clinical follow-up and characterize the diagnostic certainty increase over time.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients with “possible PSP” or “suggestive of PSP” diagnosis and clinical follow-up were recruited in two German multicenter longitudinal observational studies (ProPSP and DescribePSP). The cumulative percentage of patients longitudinally increasing diagnostic certainty was assessed over up to 2.5 years of follow-up. The sample size per arm required to detect 30% attenuated rate in diagnostic certainty increase in trials was estimated over multiple time intervals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 254 patients with available longitudinal data, 61 patients had low diagnostic certainty at baseline (48 suggestive of PSP, 13 possible PSP) and multiple clinical visits (median: 3, range: 2–4). The cumulative percentage of patients increasing diagnostic certainty progressed with follow-up duration (30.4% at 6 months, 51.7% at 1 year, 80.4% at 2.5 years). The sample size required to detect 30% reduction in diagnostic certainty increase rate within 1 year was 163, slightly smaller than that required using the PSP rating scale.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Most “suggestive of PSP” patients increased diagnostic certainty upon longitudinal follow-up, providing the first prospective multicenter validation of MDS-PSP diagnostic criteria. Our data support the design of trials tailored for these early-stage patients, suggesting the PSP rating scale and the diagnostic certainty increase rate as potential endpoint measures. © 2025 The Author(s). <i>Movement Disorders</i> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.</p>\u0000 </section>\u0000 </div>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"40 3","pages":"526-536"},"PeriodicalIF":7.4,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142963251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two Families with ANO10-Related Spinocerebellar Ataxia with Novel Exon Deletions: A First Report from India","authors":"Vikram V. Holla MD, DM,&nbsp;Nitish Kamble MD, DM,&nbsp;Reghunathan Sindhu Harishma MD,&nbsp;Gautham Arunachal MD,&nbsp;Ravi Yadav MD, DM,&nbsp;Pramod Kumar Pal MD, DNB, DM, FRCP","doi":"10.1002/mds.30107","DOIUrl":"10.1002/mds.30107","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"40 2","pages":"385-386"},"PeriodicalIF":7.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rigidity in Parkinson's Disease: The Objective Effect of Levodopa.","authors":"Marco Falletti, Francesco Asci, Alessandro Zampogna, Martina Patera, Giulia Pinola, Diego Centonze, Mark Hallett, John Rothwell, Antonio Suppa","doi":"10.1002/mds.30114","DOIUrl":"https://doi.org/10.1002/mds.30114","url":null,"abstract":"<p><strong>Background: </strong>Quantitative evidence of levodopa-induced beneficial effects on parkinsonian rigidity in Parkinson's disease (PD) is lacking. Recent research has demonstrated the velocity-dependent nature of objective rigidity in PD and revealed its neural underpinning.</p><p><strong>Objective: </strong>The present study aimed to examine the effect of levodopa on objective rigidity in PD.</p><p><strong>Methods: </strong>Eighteen patients with PD underwent clinical and instrumental evaluations of muscle tone in the OFF and ON states. The clinical assessments focused on rigidity in the most affected upper limb. The biomechanical components of objective rigidity were assessed using robot-assisted wrist extensions at seven angular velocities (5-280°/s). Surface electromyography of the flexor carpi radialis muscle enabled the concurrent evaluation of short- and long-latency stretch reflexes (SLR and LLR).</p><p><strong>Results: </strong>Levodopa improved the clinical scores of rigidity. Biomechanical measurements showed that levodopa reduced the total and neural components of force but had no effect on viscoelastic components. Levodopa reduced the velocity dependence of the LLRs but did not affect the SLRs. Finally, we found significant clinical-instrumental correlations between levodopa-induced changes and biomechanical and neurophysiological measures of objective rigidity in PD.</p><p><strong>Conclusions: </strong>Levodopa improved objective rigidity in PD by decreasing its biomechanical neural component as well as the size of LLRs. The beneficial effect of levodopa on biomechanical and neurophysiological features of objective rigidity was related to the specific angular velocity of wrist extensions; that is, the higher the angular velocity, the greater the beneficial impact of levodopa on objective rigidity. These findings allowed the description of a new pathophysiological model of rigidity in PD. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.</p>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Lows of High Reward: Choking Under Pressure","authors":"Anna Sadnicka MBChB, PhD,&nbsp;Mark J. Edwards MBBS, PhD","doi":"10.1002/mds.30092","DOIUrl":"10.1002/mds.30092","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"40 2","pages":"243-244"},"PeriodicalIF":7.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to: “Two Families with ANO10-Related Spinocerebellar Ataxia with Novel Exon Deletions: A First Report from India”","authors":"Andona Milovanović MD,&nbsp;Ana Westenberger PhD,&nbsp;Nataša Dragašević-Mišković MD","doi":"10.1002/mds.30108","DOIUrl":"10.1002/mds.30108","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"40 2","pages":"387-388"},"PeriodicalIF":7.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shining a Spotlight on Dementia with Lewy Bodies in Latin America","authors":"Miguel Germán Borda MD, PhD,&nbsp;Felipe Botero-Rodríguez MD,&nbsp;José Manuel Santacruz-Escudero MD, PhD,&nbsp;Carlos Cano-Gutiérrez MD,&nbsp;Dag Aarsland MD, PhD,&nbsp;COL-DLB","doi":"10.1002/mds.30110","DOIUrl":"10.1002/mds.30110","url":null,"abstract":"&lt;p&gt;A rapidly aging population presents significant health and social challenges, with one of the most pressing being the growing prevalence of chronic diseases, particularly age-related conditions like dementia. Already highly prevalent, dementia is projected to see a disproportionate global increase of approximately 300% in the coming decades, highlighting the urgency for effective interventions and support systems.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Research efforts must prioritize meeting the health demands of this aging population. Dementia is highly disabling and profoundly impacts not only the quality of life of individuals but also the well-being of their families. Furthermore, it places substantial economic strain on health systems.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Alzheimer's disease (AD) is the most prevalent neurodegenerative disease.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Significant global efforts have been made to improve its early detection and treatment. Innovations such as education campaigns, the development of blood-based biomarkers, and the recent approval of monoclonal antibodies represent noteworthy advancements.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Dementia with Lewy Bodies (DLB), clinically characterized by progressive dementia, parkinsonism, visual hallucinations, REM sleep behavioral disorders, and fluctuating cognition, constitutes the second most common neurodegenerative dementia after AD. Differential diagnosis can be supported by imaging techniques such as dopamine transporter single-photon emission computed tomography (SPECT), iodine-123-metaiodobenzylguanidine (MIBG), and metabolic positron emission tomography (PET).&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Estimates suggest that DLB accounts for approximately 5% of the general population and up to 30% of all dementia cases.&lt;span&gt;&lt;sup&gt;5, 6&lt;/sup&gt;&lt;/span&gt; Studies calculate that approximately 4.2% of dementia cases among older adults living in the community and 7.5% in specialized care settings are DLB.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; Individuals living with DLB experience a significantly worse clinical trajectory compared to those with AD or other types of dementia, including a more rapid functional decline, increased dependency, and a higher risk of complications, such as severe neuropsychiatric symptoms and motor impairments.&lt;span&gt;&lt;sup&gt;7-9&lt;/sup&gt;&lt;/span&gt; These factors contribute to a markedly reduced quality of life for individuals and their families. Mortality rates are also higher in DLB patients due to the complex interplay of cognitive, behavioral, and physical symptoms, as well as the increased susceptibility to comorbidities.&lt;span&gt;&lt;sup&gt;10&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;The impact of DLB extends beyond the individual diagnosed with the disease, placing a significant burden on caregivers. Family members and healthcare providers often experience considerable emotional and physical stress due to the disease's unpredictable progression, frequent behavioral disturbances, and the intensive care needs of patients. Additionally, t","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"40 2","pages":"222-225"},"PeriodicalIF":7.4,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mds.30110","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial DNA Copy Number as a Potential Biomarker for the Severity of Motor Symptoms and Prognosis in Parkinson's Disease","authors":"Sungyang Jo MD, PhD,&nbsp;Ji-Hye Oh PhD,&nbsp;Eun-Jae Lee MD, PhD,&nbsp;Moongwan Choi MD,&nbsp;Jihyun Lee MD,&nbsp;Sangjin Lee MD,&nbsp;Tae Won Kim MD, PhD,&nbsp;Chang Ohk Sung MD, PhD,&nbsp;Sun Ju Chung MD, PhD","doi":"10.1002/mds.30098","DOIUrl":"10.1002/mds.30098","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Mitochondrial function influences Parkinson's disease (PD) through the accumulation of pathogenic alpha-synuclein, oxidative stress, impaired autophagy, and neuroinflammation. The mitochondrial DNA copy number (mtDNA-CN), representing the number of mitochondrial DNA copies within a cell, serves as an easily assessable proxy for mitochondrial function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to assess the diagnostic and prognostic capabilities of mtDNA-CN in PD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We assessed mtDNA-CN in blood samples using whole genome sequencing from 405 patients with PD and 200 healthy controls (HC). We examined the relationship between mtDNA-CN levels and motor symptom severity in PD, as well as their association with dementia development in patients with early-PD (within 3 years of diagnosis).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>mtDNA-CN levels were significantly lower in patients with PD compared with HC (<i>P</i> = 1.1 × 10⁻⁵). A negative correlation was discovered between mtDNA-CN level and motor severity in PD (correlation coefficient = −0.20; <i>P</i> = 0.008). Among 210 patients with early-PD, Cox regression analysis demonstrated an association between lower mtDNA-CN levels and a higher risk of developing dementia (hazard ratio [HR] = 0.41, 95% confidence interval: 0.20–0.86, <i>P</i> = 0.02), even after adjusting for age and blood cell count (HR = 0.41, 95% confidence interval: 0.18–0.92, <i>P</i> = 0.03). However, mtDNA-CN levels did not significantly correlate with motor progression in PD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings suggest that blood mtDNA-CN may function as a diagnostic biomarker for PD and a prognostic marker for dementia in patients with PD. © 2025 International Parkinson and Movement Disorder Society.</p>\u0000 </section>\u0000 </div>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"40 3","pages":"502-510"},"PeriodicalIF":7.4,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}