Pub Date : 2025-02-03DOI: 10.1016/j.parkreldis.2025.107311
Alice Saparov, Michael Zech
The current era of high-throughput analysis-driven research offers invaluable insights into disease etiologies, accurate diagnostics, pathogenesis, and personalized therapy. In the field of movement disorders, investigators are facing an increasing growth in the volume of produced patient-derived datasets, providing substantial opportunities for precision medicine approaches based on extensive information accessibility and advanced annotation practices. Integrating data from multiple sources, including phenomics, genomics, and multi-omics, is crucial for comprehensively understanding different types of movement disorders. Here, we explore formats and analytics of big data generated for patients with movement disorders, including strategies to meaningfully share the data for optimized patient benefit. We review computational methods that are essential to accelerate the process of evaluating the increasing amounts of specialized data collected. Based on concrete examples, we highlight how bioinformatic approaches facilitate the translation of multidimensional biological information into clinically relevant knowledge. Moreover, we outline the feasibility of computer-aided therapeutic target evaluation, and we discuss the importance of expanding the focus of big data research to understudied phenotypes such as dystonia.
{"title":"Big data and transformative bioinformatics in genomic diagnostics and beyond.","authors":"Alice Saparov, Michael Zech","doi":"10.1016/j.parkreldis.2025.107311","DOIUrl":"https://doi.org/10.1016/j.parkreldis.2025.107311","url":null,"abstract":"<p><p>The current era of high-throughput analysis-driven research offers invaluable insights into disease etiologies, accurate diagnostics, pathogenesis, and personalized therapy. In the field of movement disorders, investigators are facing an increasing growth in the volume of produced patient-derived datasets, providing substantial opportunities for precision medicine approaches based on extensive information accessibility and advanced annotation practices. Integrating data from multiple sources, including phenomics, genomics, and multi-omics, is crucial for comprehensively understanding different types of movement disorders. Here, we explore formats and analytics of big data generated for patients with movement disorders, including strategies to meaningfully share the data for optimized patient benefit. We review computational methods that are essential to accelerate the process of evaluating the increasing amounts of specialized data collected. Based on concrete examples, we highlight how bioinformatic approaches facilitate the translation of multidimensional biological information into clinically relevant knowledge. Moreover, we outline the feasibility of computer-aided therapeutic target evaluation, and we discuss the importance of expanding the focus of big data research to understudied phenotypes such as dystonia.</p>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":" ","pages":"107311"},"PeriodicalIF":3.1,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383025","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}
Essential tremor (ET) is a progressive disorder characterized by altered network connectivity between the cerebellum, thalamus, and cortical regions. Magnetic Resonance-guided Focused Ultrasound (MRgFUS) of the ventral intermediate nucleus (VIM) is an effective, minimally invasive treatment for ET. The impact of MRgFUS interventions on regional Gray Matter Volume (GMV) are as yet not well understood.
Methods
Forty-six patients with medication-resistant ET underwent unilateral VIM-MRgFUS. Voxel-based morphometry was applied to investigate GMV changes over a time span of 6 months in the whole brain and the thalamus in particular to investigate local and distant effects.
Results
Clinically, contralateral tremor significantly decreased by 68 % at 6 months following MRgFUS. In addition to local GMV decreases in thalamic nuclei (VIM, ventral lateral posterior, centromedian thalamus and pulvinar), VBM revealed remote GMV decreases in the ipsilesional insula and the anterior cingulate cortex as well as the contralesional middle occipital gyrus. Increased GMV was found in the right superior and middle temporal gyrus, as well as in the left inferior temporal gyrus. There was no significant correlation between regional GMV declines and tremor improvement. However, temporal volume increases were associated with improved motor-related functional abilities and quality of life outcomes.
Conclusion
Our findings implicate distributed structural changes following unilateral VIM-MRgFUS. Structural losses could reflect Wallerian degeneration of VIM output neurons or plasticity due to decreased sensory input following tremor improvement.
{"title":"Beyond the cerebello-thalamo-cortical tract: Remote structural changes after VIM-MRgFUS in essential tremor","authors":"Jonas Krauss , Neeraj Upadhyay , Veronika Purrer , Valeri Borger , Marcel Daamen , Angelika Maurer , Carsten Schmeel , Alexander Radbruch , Ullrich Wüllner , Henning Boecker","doi":"10.1016/j.parkreldis.2025.107318","DOIUrl":"10.1016/j.parkreldis.2025.107318","url":null,"abstract":"<div><h3>Introduction</h3><div>Essential tremor (ET) is a progressive disorder characterized by altered network connectivity between the cerebellum, thalamus, and cortical regions. Magnetic Resonance-guided Focused Ultrasound (MRgFUS) of the ventral intermediate nucleus (VIM) is an effective, minimally invasive treatment for ET. The impact of MRgFUS interventions on regional Gray Matter Volume (GMV) are as yet not well understood.</div></div><div><h3>Methods</h3><div>Forty-six patients with medication-resistant ET underwent unilateral VIM-MRgFUS. Voxel-based morphometry was applied to investigate GMV changes over a time span of 6 months in the whole brain and the thalamus in particular to investigate local and distant effects.</div></div><div><h3>Results</h3><div>Clinically, contralateral tremor significantly decreased by 68 % at 6 months following MRgFUS. In addition to local GMV decreases in thalamic nuclei (VIM, ventral lateral posterior, centromedian thalamus and pulvinar), VBM revealed remote GMV decreases in the ipsilesional insula and the anterior cingulate cortex as well as the contralesional middle occipital gyrus. Increased GMV was found in the right superior and middle temporal gyrus, as well as in the left inferior temporal gyrus. There was no significant correlation between regional GMV declines and tremor improvement. However, temporal volume increases were associated with improved motor-related functional abilities and quality of life outcomes.</div></div><div><h3>Conclusion</h3><div>Our findings implicate distributed structural changes following unilateral VIM-MRgFUS. Structural losses could reflect Wallerian degeneration of VIM output neurons or plasticity due to decreased sensory input following tremor improvement.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"132 ","pages":"Article 107318"},"PeriodicalIF":3.1,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364663","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}
Pub Date : 2025-02-01DOI: 10.1016/j.parkreldis.2024.107239
R.A. Hauser , H.H. Fernandez , J. Jimenez-Shahed , S. Allard , G. Banisadr , S. Fisher , R. D'Souza
Background
For Parkinson's disease patients with motor fluctuations, the duration of benefit per levodopa dose is a key metric that reflects a patient's clinical response.
Objective
Determine the difference in mean durations of “Good On” time per dose of subjects randomized to extended-release carbidopa-levodopa (ER CD-LD; IPX203; CREXONT®) vs. immediate-release (IR) CD-LD in the RISE-PD trial.
Methods
“Good On” time per dose was assessed at the end of the IR CD-LD dose adjustment phase (Visit 2/Week 3) and compared to End of Study (Visit 7/EOS) between IPX203 and IR CD-LD groups. In addition, to understand if “Good On” time per dose for IR CD-LD before conversion to IPX203 could impact the magnitude of change in “Good On” time per dose of IPX203 vs. IR CD-LD after conversion, subjects were rank-ordered and divided into quartiles based on their initial “Good On” time per dose optimized IR CD-LD values. Changes in “Good On” time per dose between IPX203 and IR CD-LD groups were then compared for each quartile from Visit 2 to EOS.
Results
IPX203 increased “Good On” time per dose compared to IR CD-LD by a mean of 1.6 h (p < 0.0001). The mean differences in “Good On” time per dose between IPX203 and IR CD-LD were 1.53h for quartile one, 1.39h for quartile two, 1.83h for quartile three, and 1.56h for quartile four (p < 0.0001 for all quartiles).
Conclusion
IPX203 significantly increased “Good On” time per dose regardless of the duration of “Good On” time per dose observed with IR CD-LD.
{"title":"Duration of “Good On” time per dose: Immediate-release carbidopa-levodopa vs. extended-release carbidopa-levodopa (IPX203, CREXONT®)","authors":"R.A. Hauser , H.H. Fernandez , J. Jimenez-Shahed , S. Allard , G. Banisadr , S. Fisher , R. D'Souza","doi":"10.1016/j.parkreldis.2024.107239","DOIUrl":"10.1016/j.parkreldis.2024.107239","url":null,"abstract":"<div><h3>Background</h3><div>For Parkinson's disease patients with motor fluctuations, the duration of benefit per levodopa dose is a key metric that reflects a patient's clinical response.</div></div><div><h3>Objective</h3><div>Determine the difference in mean durations of “Good On” time per dose of subjects randomized to extended-release carbidopa-levodopa (ER CD-LD; IPX203; CREXONT®) vs. immediate-release (IR) CD-LD in the RISE-PD trial.</div></div><div><h3>Methods</h3><div>“Good On” time per dose was assessed at the end of the IR CD-LD dose adjustment phase (Visit 2/Week 3) and compared to End of Study (Visit 7/EOS) between IPX203 and IR CD-LD groups. In addition, to understand if “Good On” time per dose for IR CD-LD before conversion to IPX203 could impact the magnitude of change in “Good On” time per dose of IPX203 vs. IR CD-LD after conversion, subjects were rank-ordered and divided into quartiles based on their initial “Good On” time per dose optimized IR CD-LD values. Changes in “Good On” time per dose between IPX203 and IR CD-LD groups were then compared for each quartile from Visit 2 to EOS.</div></div><div><h3>Results</h3><div>IPX203 increased “Good On” time per dose compared to IR CD-LD by a mean of 1.6 h (p < 0.0001). The mean differences in “Good On” time per dose between IPX203 and IR CD-LD were 1.53h for quartile one, 1.39h for quartile two, 1.83h for quartile three, and 1.56h for quartile four (p < 0.0001 for all quartiles).</div></div><div><h3>Conclusion</h3><div>IPX203 significantly increased “Good On” time per dose regardless of the duration of “Good On” time per dose observed with IR CD-LD.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"131 ","pages":"Article 107239"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903159","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}
Pub Date : 2025-02-01DOI: 10.1016/j.parkreldis.2024.107250
Christof Brücke , Thomas Brücke , Walter Pirker , Alexander Zimprich
Background
Variants in the UQCRC1 gene have been proposed to cause autosomal dominant Parkinson's disease with neuropathy. However, definitive confirmation of UQCRC1 as an authentic Parkinson's gene remains elusive, as follow-up studies have not yet provided conclusive evidence.
Methods
382 Austrian Parkinson's patients, particularly selected for familial and/or early onset cases, were Exome sequenced.
Results
We found three unrelated patients with a positive family history of the disease who shared the same rare missense variant in the UQCRC1 gene: c.1214G > T; p.(Gly405Val). The variant is very rare in the control population, with an allele frequency of 2 × 10−6 in the gnomAD database. None of the three patients carries a rare variant in a monogenic Parkinson's disease gene.
Conclusion
We suggest that UQCRC1 p.(Gly405Val) probably contributes to the development of the disease in these three patients. Our findings provide further evidence that UQCRC1 is a ‘bona fide’ Parkinson's disease gene.
{"title":"A rare variant in the UQCRC1 gene, p.(Gly405Val) in three Austrian Parkinson's patients","authors":"Christof Brücke , Thomas Brücke , Walter Pirker , Alexander Zimprich","doi":"10.1016/j.parkreldis.2024.107250","DOIUrl":"10.1016/j.parkreldis.2024.107250","url":null,"abstract":"<div><h3>Background</h3><div>Variants in the <em>UQCRC1</em> gene have been proposed to cause autosomal dominant Parkinson's disease with neuropathy. However, definitive confirmation of <em>UQCRC1</em> as an authentic Parkinson's gene remains elusive, as follow-up studies have not yet provided conclusive evidence.</div></div><div><h3>Methods</h3><div>382 Austrian Parkinson's patients, particularly selected for familial and/or early onset cases, were Exome sequenced.</div></div><div><h3>Results</h3><div>We found three unrelated patients with a positive family history of the disease who shared the same rare missense variant in the <em>UQCRC1</em> gene: c.1214G > T; p.(Gly405Val). The variant is very rare in the control population, with an allele frequency of 2 × 10<sup>−6</sup> in the gnomAD database. None of the three patients carries a rare variant in a monogenic Parkinson's disease gene.</div></div><div><h3>Conclusion</h3><div>We suggest that <em>UQCRC1</em> p.(Gly405Val) probably contributes to the development of the disease in these three patients. Our findings provide further evidence that <em>UQCRC1</em> is a ‘bona fide’ Parkinson's disease gene.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"131 ","pages":"Article 107250"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927742","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":"Commentary on “The use of hypoglycemic drugs in Parkinson's disease: An updated meta-analysis of randomized controlled trials”","authors":"Shubham Kumar , Ahmad Neyazi , Rachana Mehta , Ranjana Sah","doi":"10.1016/j.parkreldis.2024.107247","DOIUrl":"10.1016/j.parkreldis.2024.107247","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"131 ","pages":"Article 107247"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896674","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}
Progressive supranuclear palsy (PSP) involves midbrain structures, including the red nucleus (RN), an iron-rich region that appears as a high-contrast area on quantitative susceptibility mapping (QSM). RN may serve as a promising biomarker for differentiating parkinsonism. However, RN deformation in PSP remains elusive. This study aimed to evaluate RN deformation in PSP using coronal QSM images and compare them with those of Parkinson's disease (PD) and healthy controls (HC).
Methods
We evaluated the QSM images of 22 patients with PSP, 37 patients with PD, and 43 HC. We developed a grading system to assess RN deformation on coronal QSM images and classified them into three grades. The midbrain and RN volumes were extracted using distinct approaches, and their relationship with grading was investigated. For validation, coronal QSM images of 16 PSP patients from a different institution were assessed.
Results
In PSP, 59 % of the patients displayed a flattened RN of grade 3, which we termed a Rice-Grain Appearance. The volume reductions in midbrain and RN were associated with deformation. Differentiation based on the presence of this appearance yielded a specificity of 1.000 (CI: 1.000–1.000) and sensitivity of 0.591 (0.385–0.796) for distinguishing PSP from others. Secondary dataset also showed that 56 % of patients with PSP were classified as grade 3.
Conclusion
In coronal QSM images, the flattened RN shape appears to be specific to PSP compared to PD and HC and may serve as a marker to help differentiate PSP in future clinical settings.
{"title":"Flattened red nucleus in progressive supranuclear palsy detected by quantitative susceptibility mapping","authors":"Kazuya Kawabata , Fumihiko Banno , Yasuaki Mizutani , Toshiki Maeda , Ryunosuke Nagao , Sayuri Shima , Kazuhiro Murayama , Yoshiharu Ohno , Tetsuya Maeda , Makoto Sasaki , Akihiro Ueda , Mizuki Ito , Hirohisa Watanabe","doi":"10.1016/j.parkreldis.2024.107251","DOIUrl":"10.1016/j.parkreldis.2024.107251","url":null,"abstract":"<div><h3>Introduction</h3><div>Progressive supranuclear palsy (PSP) involves midbrain structures, including the red nucleus (RN), an iron-rich region that appears as a high-contrast area on quantitative susceptibility mapping (QSM). RN may serve as a promising biomarker for differentiating parkinsonism. However, RN deformation in PSP remains elusive. This study aimed to evaluate RN deformation in PSP using coronal QSM images and compare them with those of Parkinson's disease (PD) and healthy controls (HC).</div></div><div><h3>Methods</h3><div>We evaluated the QSM images of 22 patients with PSP, 37 patients with PD, and 43 HC. We developed a grading system to assess RN deformation on coronal QSM images and classified them into three grades. The midbrain and RN volumes were extracted using distinct approaches, and their relationship with grading was investigated. For validation, coronal QSM images of 16 PSP patients from a different institution were assessed.</div></div><div><h3>Results</h3><div>In PSP, 59 % of the patients displayed a flattened RN of grade 3, which we termed a Rice-Grain Appearance. The volume reductions in midbrain and RN were associated with deformation. Differentiation based on the presence of this appearance yielded a specificity of 1.000 (CI: 1.000–1.000) and sensitivity of 0.591 (0.385–0.796) for distinguishing PSP from others. Secondary dataset also showed that 56 % of patients with PSP were classified as grade 3.</div></div><div><h3>Conclusion</h3><div>In coronal QSM images, the flattened RN shape appears to be specific to PSP compared to PD and HC and may serve as a marker to help differentiate PSP in future clinical settings.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"131 ","pages":"Article 107251"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896684","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}
Pub Date : 2025-02-01DOI: 10.1016/j.parkreldis.2024.107241
Angelo F. Gigante , Mark Hallett , Hyder A. Jinnah , Alfredo Berardelli , Joel S. Perlmutter , Brian D. Berman , Joseph Jankovic , Tobias Bäumer , Cynthia Comella , Tommaso Ercoli , Daniele Belvisi , Susan H. Fox , Han-Joon Kim , Emile Sami Moukheiber , Sarah Pirio Richardson , Anne Weissbach , Antonella Muroni , Giovanni Defazio
Introduction
Idiopathic blepharospasm is a clinically heterogeneous form of focal dystonia, also associated with psychiatric symptoms. The identification of the most relevant sets of motor and psychiatric manifestations may help better understand the specific phenomenology of the condition and delineate blepharospasm subtypes more accurately.
Methods
Patients with idiopathic blepharospasm were from the Dystonia Coalition project. Factor analysis of several motor and psychiatric scales was performed to identify the relevant determinants of blepharospasm severity. The selected items were then used in a data-driven cluster analysis to subtype blepharospasm individuals.
Results
Factor analysis reduced the many variables in the motor and psychiatric scales to 13 variables distributed in four factors. When the four sets were used as clustering variables, three blepharospasm clusters were identified: cluster 1 was characterized by low levels of motor and psychiatric factors; cluster 2 showed high levels of both motor and psychiatric factors; and cluster 3 showed high levels of psychiatric factors (similar to cluster 2) but low level of motor factors (similar to that of cluster 1).
Conclusions
Factor analysis enabled the identification of key motor and psychiatric determinants of blepharospasm severity. The derived factor sets provide a streamlined tool for predicting and measuring these dimensions. This approach also facilitated more precise cluster analysis and improved recognition of clinical subtypes.
{"title":"Factor analysis and clustering of motor and psychiatric dimensions in idiopathic blepharospasm","authors":"Angelo F. Gigante , Mark Hallett , Hyder A. Jinnah , Alfredo Berardelli , Joel S. Perlmutter , Brian D. Berman , Joseph Jankovic , Tobias Bäumer , Cynthia Comella , Tommaso Ercoli , Daniele Belvisi , Susan H. Fox , Han-Joon Kim , Emile Sami Moukheiber , Sarah Pirio Richardson , Anne Weissbach , Antonella Muroni , Giovanni Defazio","doi":"10.1016/j.parkreldis.2024.107241","DOIUrl":"10.1016/j.parkreldis.2024.107241","url":null,"abstract":"<div><h3>Introduction</h3><div>Idiopathic blepharospasm is a clinically heterogeneous form of focal dystonia, also associated with psychiatric symptoms. The identification of the most relevant sets of motor and psychiatric manifestations may help better understand the specific phenomenology of the condition and delineate blepharospasm subtypes more accurately.</div></div><div><h3>Methods</h3><div>Patients with idiopathic blepharospasm were from the Dystonia Coalition project. Factor analysis of several motor and psychiatric scales was performed to identify the relevant determinants of blepharospasm severity. The selected items were then used in a data-driven cluster analysis to subtype blepharospasm individuals.</div></div><div><h3>Results</h3><div>Factor analysis reduced the many variables in the motor and psychiatric scales to 13 variables distributed in four factors. When the four sets were used as clustering variables, three blepharospasm clusters were identified: cluster 1 was characterized by low levels of motor and psychiatric factors; cluster 2 showed high levels of both motor and psychiatric factors; and cluster 3 showed high levels of psychiatric factors (similar to cluster 2) but low level of motor factors (similar to that of cluster 1).</div></div><div><h3>Conclusions</h3><div>Factor analysis enabled the identification of key motor and psychiatric determinants of blepharospasm severity. The derived factor sets provide a streamlined tool for predicting and measuring these dimensions. This approach also facilitated more precise cluster analysis and improved recognition of clinical subtypes.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"131 ","pages":"Article 107241"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896683","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}
Pub Date : 2025-02-01DOI: 10.1016/j.parkreldis.2024.107254
Ihtsham U. Haq , Eleonora Napoli , Beverly M. Snively , Marina L. Sarno , Kathleen J. Sweadner , Laurie J. Ozelius , Allison Brashear
Introduction
The onset of symptoms in Rapid-onset dystonia-parkinsonism (RDP) is typically over days to weeks and is often triggered by stressors like fever or childbirth. Limited information is available on how the motor and nonmotor symptoms evolve over the course of the disease. Our longitudinal study analyzed data from a cohort of RDP patients, documenting their symptoms across multiple visits.
Methods
We characterized the phenotypic evolution of 14 individuals positive for ATP1A3 mutations (7 females, 7 males; mean examination age = 37 years, mean age of onset = 20 years). We focused on neurologic, cognitive, and neuropsychological data collected during in-person visits (mean interval between testing = 5½ years).
Results
Initially, all participants exhibited bulbar symptoms. Headaches were noted in 50 %, seizures in 31 %, and tremors in 36 %. At follow-up, 29 % of those initially without headaches developed them, 22 % without prior seizures experienced them, and 56 % previously without tremors developed them. No improvements were seen in those with headaches; however, seizures and tremors improved in 25 % and 80 % of cases, respectively. For Burke-Fahn-Marsden Dystonia Rating Scale, Unified Parkinson's Disease Rating Scale, and International Cooperative Ataxia Rating Scale scores, improvement consisted of the reduction of the symptom. Cognitive functions improved from mildly impaired to low-average, and psychiatric evaluations indicated mild anxiety levels, slight increases in obsessive-compulsive behaviors, and decreased depression scores over time.
Conclusions
This longitudinal analysis highlights the complex evolution of RDP, demonstrating significant variability in motor function and other symptoms such as headaches, seizures, and tremors.
{"title":"Neurological and psychiatric characterization of rapid-onset dystonia-parkinsonism over time","authors":"Ihtsham U. Haq , Eleonora Napoli , Beverly M. Snively , Marina L. Sarno , Kathleen J. Sweadner , Laurie J. Ozelius , Allison Brashear","doi":"10.1016/j.parkreldis.2024.107254","DOIUrl":"10.1016/j.parkreldis.2024.107254","url":null,"abstract":"<div><h3>Introduction</h3><div>The onset of symptoms in Rapid-onset dystonia-parkinsonism (RDP) is typically over days to weeks and is often triggered by stressors like fever or childbirth. Limited information is available on how the motor and nonmotor symptoms evolve over the course of the disease. Our longitudinal study analyzed data from a cohort of RDP patients, documenting their symptoms across multiple visits.</div></div><div><h3>Methods</h3><div>We characterized the phenotypic evolution of 14 individuals positive for ATP1A3 mutations (7 females, 7 males; mean examination age = 37 years, mean age of onset = 20 years). We focused on neurologic, cognitive, and neuropsychological data collected during in-person visits (mean interval between testing = 5½ years).</div></div><div><h3>Results</h3><div>Initially, all participants exhibited bulbar symptoms. Headaches were noted in 50 %, seizures in 31 %, and tremors in 36 %. At follow-up, 29 % of those initially without headaches developed them, 22 % without prior seizures experienced them, and 56 % previously without tremors developed them. No improvements were seen in those with headaches; however, seizures and tremors improved in 25 % and 80 % of cases, respectively. For Burke-Fahn-Marsden Dystonia Rating Scale, Unified Parkinson's Disease Rating Scale, and International Cooperative Ataxia Rating Scale scores, improvement consisted of the reduction of the symptom. Cognitive functions improved from mildly impaired to low-average, and psychiatric evaluations indicated mild anxiety levels, slight increases in obsessive-compulsive behaviors, and decreased depression scores over time.</div></div><div><h3>Conclusions</h3><div>This longitudinal analysis highlights the complex evolution of RDP, demonstrating significant variability in motor function and other symptoms such as headaches, seizures, and tremors.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"131 ","pages":"Article 107254"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896685","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}
Pub Date : 2025-02-01DOI: 10.1016/j.parkreldis.2024.107229
Taylor Brown , Prabesh Kanel , Alexis Griggs , Giulia Carli , Robert Vangel , Roger L. Albin , Nicolaas I. Bohnen
Visual and visual processing deficits are implicated in freezing, falling, and cognitive impairments in Parkinson's disease (PD). In particular, contrast sensitivity deficits are common and may be related to cognitive impairment in PD. While dopaminergic deficits play a role in PD-related visual dysfunction, brain cholinergic systems also modulate many aspects of visual processing. The aim of this study was to explore regional cerebral cholinergic terminal density correlates of contrast sensitivity in PD. Ninety-one PD subjects underwent contrast sensitivity testing, motor testing, cognitive testing, and brain MRI and [18F]-fluoroethoxybenzovesamicol [18F]-FEOBV PET imaging. Whole brain false discovery error-corrected (p < 0.05) correlations revealed significant associations between VAChT deficits in pericentral, limbic, and visual processing regions and contrast sensitivity performance, independent of disease duration and dopaminergic medication doses. These results suggest that brain cholinergic deficits correlate with contrast sensitivity deficits in PD. Additionally, decreased Rabin contrast sensitivity scores were associated with lower total scores in the Parkinson's Disease Cognitive Rating Scale. These findings suggest that diminished cognitive performance correlated with contrast sensitivity partly reflects underlying vulnerabilities of brain cholinergic systems.
{"title":"Regional cerebral cholinergic vesicular transporter correlates of visual contrast sensitivity in Parkinson's disease: Implications for visual and cognitive function","authors":"Taylor Brown , Prabesh Kanel , Alexis Griggs , Giulia Carli , Robert Vangel , Roger L. Albin , Nicolaas I. Bohnen","doi":"10.1016/j.parkreldis.2024.107229","DOIUrl":"10.1016/j.parkreldis.2024.107229","url":null,"abstract":"<div><div>Visual and visual processing deficits are implicated in freezing, falling, and cognitive impairments in Parkinson's disease (PD). In particular, contrast sensitivity deficits are common and may be related to cognitive impairment in PD. While dopaminergic deficits play a role in PD-related visual dysfunction, brain cholinergic systems also modulate many aspects of visual processing. The aim of this study was to explore regional cerebral cholinergic terminal density correlates of contrast sensitivity in PD. Ninety-one PD subjects underwent contrast sensitivity testing, motor testing, cognitive testing, and brain MRI and [<sup>18</sup>F]-fluoroethoxybenzovesamicol [<sup>18</sup>F]-FEOBV PET imaging. Whole brain false discovery error-corrected (<em>p</em> < 0.05) correlations revealed significant associations between VAChT deficits in pericentral, limbic, and visual processing regions and contrast sensitivity performance, independent of disease duration and dopaminergic medication doses. These results suggest that brain cholinergic deficits correlate with contrast sensitivity deficits in PD. Additionally, decreased Rabin contrast sensitivity scores were associated with lower total scores in the Parkinson's Disease Cognitive Rating Scale. These findings suggest that diminished cognitive performance correlated with contrast sensitivity partly reflects underlying vulnerabilities of brain cholinergic systems.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"131 ","pages":"Article 107229"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854738","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}
Pub Date : 2025-02-01DOI: 10.1016/j.parkreldis.2025.107260
Martje G. Pauly , Mirja Thomsen , Vera Tadic , Hauke Busch , Christel Depienne , Katja Lohmann , Christine Klein , Norbert Brüggemann
{"title":"Insufficient effect of deep brain stimulation in a patient with KCNN2-associated myoclonus-dystonia","authors":"Martje G. Pauly , Mirja Thomsen , Vera Tadic , Hauke Busch , Christel Depienne , Katja Lohmann , Christine Klein , Norbert Brüggemann","doi":"10.1016/j.parkreldis.2025.107260","DOIUrl":"10.1016/j.parkreldis.2025.107260","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"131 ","pages":"Article 107260"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952864","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}
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