Guedi Ali Barreh, I. Sghaier, Y. Abida, A. Gharbi, A. Nasri, S. Mrabet, A. Souissi, M. Djebara, Sameh Trabelsi, I. Kacem, Amina Gargouri-Berrachi, R. Gouider
Background LRRK2-G2019S is the most frequent mutation in North African Parkinson's disease (PD) patients.Data on its impact on disease progression and treatment response remains elusive.Therefore, we aimed to explore the clinical features,treatments,and complications through the disease course of PD Tunisian patients according to their LRRK2-G2019S profile. Methods Longitudinal retrospective study conducted in the department of Neurology,Razi University Hospital.We included clinically diagnosed PD patients according to the MDS criteria and reviewed their medical records for clinical,treatment, and neuropsychological assessments.LRRK2-G2019S mutation was screened among all cases using Sanger sequencing.The correlation of LRRK2-G2019S and the clinical PD features was then evaluated. Results We included 393 PD patients with 41.5% of cases were mutated for LRRK2-G2019S. Those with mutation exhibited an earlier age of onset(p=0.017),and female-PD cases had a higher mutation frequency (p=0.008).Mutation carriers displayed distinct clinical features,with a higher frequency of postural instability gait difficulty (PIGD)forms(adjusted-p<0.001).Throughout the disease progression,carriers showed a faster annual progression in UPDRS-III scores (adjusted-p=0.009) and a significantly higher Levodopa Equivalent Dosevalues in later stages(1060.81 vs. 877.83 for 6-8 years).Motor complications such as dyskinesia (adjusted-p<0.001) and motor fluctuations(31.9% vs. 25.7%,adjusted-p<0.001) were more prevalent in carriers,particularly in later stages.LRRK2-G2019S carriers also exhibited a lower prevalence of non-motor symptoms including cognitive disordersfor episodic memory(adjusted-p<0.001),attention(adjusted-p<0.001),and dysexecutive disorders (adjusted-p=0.039),as well asneuropsychiatric symptoms and dysautonomic signs. Conclusion This study demonstrated the variability of clinical profile among Tunisian PD cases explained by the incomplete penetrance of LRRK2-G2019S that increases with age.Further studies with biomarker and disease progression data are necessary to improve PD management.
背景LRRK2-G2019S是北非帕金森病（PD）患者中最常见的基因突变。因此，我们旨在根据LRRK2-G2019S的特征，探讨突尼斯PD患者在整个病程中的临床特征、治疗和并发症。结果我们纳入了 393 例 PD 患者，其中 41.5% 的病例存在 LRRK2-G2019S 突变。突变携带者表现出明显的临床特征，其中体位不稳步态困难（PIGD）的频率更高（调整后p<0.001）。在整个疾病进展过程中，携带者的UPDRS-III评分年进展速度更快（调整后p=0.009），后期的左旋多巴等效剂量值明显更高（6-8年为1060.81 vs. 877.83）。运动障碍（调整后p<0.001）和运动波动（31.9% vs. 25.7%，调整后p<0.LRRK2-G2019S携带者也表现出较低的非运动症状，包括认知障碍，如外显记忆（调整后p<0.001）、注意力（调整后p<0.001）和执行障碍（调整后p=0.结论这项研究表明，LRRK2-G2019S的不完全渗透性会随着年龄的增长而增加，这也解释了突尼斯PD病例临床特征的变异性。
{"title":"LRRK2 G2019S impact on Parkinson disease; clinical phenotype and treatment in Tunisian patients.","authors":"Guedi Ali Barreh, I. Sghaier, Y. Abida, A. Gharbi, A. Nasri, S. Mrabet, A. Souissi, M. Djebara, Sameh Trabelsi, I. Kacem, Amina Gargouri-Berrachi, R. Gouider","doi":"10.14802/jmd.23276","DOIUrl":"https://doi.org/10.14802/jmd.23276","url":null,"abstract":"Background\u0000LRRK2-G2019S is the most frequent mutation in North African Parkinson's disease (PD) patients.Data on its impact on disease progression and treatment response remains elusive.Therefore, we aimed to explore the clinical features,treatments,and complications through the disease course of PD Tunisian patients according to their LRRK2-G2019S profile.\u0000\u0000\u0000Methods\u0000Longitudinal retrospective study conducted in the department of Neurology,Razi University Hospital.We included clinically diagnosed PD patients according to the MDS criteria and reviewed their medical records for clinical,treatment, and neuropsychological assessments.LRRK2-G2019S mutation was screened among all cases using Sanger sequencing.The correlation of LRRK2-G2019S and the clinical PD features was then evaluated.\u0000\u0000\u0000Results\u0000We included 393 PD patients with 41.5% of cases were mutated for LRRK2-G2019S. Those with mutation exhibited an earlier age of onset(p=0.017),and female-PD cases had a higher mutation frequency (p=0.008).Mutation carriers displayed distinct clinical features,with a higher frequency of postural instability gait difficulty (PIGD)forms(adjusted-p<0.001).Throughout the disease progression,carriers showed a faster annual progression in UPDRS-III scores (adjusted-p=0.009) and a significantly higher Levodopa Equivalent Dosevalues in later stages(1060.81 vs. 877.83 for 6-8 years).Motor complications such as dyskinesia (adjusted-p<0.001) and motor fluctuations(31.9% vs. 25.7%,adjusted-p<0.001) were more prevalent in carriers,particularly in later stages.LRRK2-G2019S carriers also exhibited a lower prevalence of non-motor symptoms including cognitive disordersfor episodic memory(adjusted-p<0.001),attention(adjusted-p<0.001),and dysexecutive disorders (adjusted-p=0.039),as well asneuropsychiatric symptoms and dysautonomic signs.\u0000\u0000\u0000Conclusion\u0000This study demonstrated the variability of clinical profile among Tunisian PD cases explained by the incomplete penetrance of LRRK2-G2019S that increases with age.Further studies with biomarker and disease progression data are necessary to improve PD management.","PeriodicalId":16372,"journal":{"name":"Journal of Movement Disorders","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140668204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Deep Brain Stimulation in Advanced Parkinson's Disease: An Uncommon Case of Allergic Encephalitis.","authors":"Jyun-Yi Chen, Yen-Chung Chen, Shey-Lin Wu","doi":"10.14802/jmd.23237","DOIUrl":"https://doi.org/10.14802/jmd.23237","url":null,"abstract":"","PeriodicalId":16372,"journal":{"name":"Journal of Movement Disorders","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140701355","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}
Yingji Li, Yang Liu, Rongfei Wang, Ran Ao, Feng Xiang, Xu Zhang, Xiangqing Wang, Shengyuan Yu
Purpose Sialidosis type 2 has variants that are both catalytically inactive (severe), while sialidosis type 1 has at least one catalytically active (mild) variant. This study aimed to discuss the structural changes associated with these variants in a newly reported family carrying NEU1 variants and explore the clinical characteristics of different combinations of variants in sialidosis type 1. Methods First, whole-exome sequencing and detailed clinical examination were performed on the family. Second, structural analysis, including energy, flexibility and polar contacts, was conducted for several NEU1 variants, and a sialidase activity assay was performed. Third, previous NEU1 variants were systematically reviewed, and the clinical characteristics of patients in the severe-mild and mild-mild groups with sialidosis type 1 were analyzed. Results We report a novel family with sialidosis type 1 and the compound heterozygous variants S182G and V143E. The newly identified V143E variant was predicted to be a mild variant through structural analysis and was confirmed by sialidase activity assay. The cherry-red spot was more prevalent in the severe-mild group, and ataxia was more common in the mild-mild group. Impaired cognition was found only in the severe-mild group. Moreover, patients with cherry-red spots and abnormal EEGs and VEPs had a relatively early age of onset, whereas patients with myoclonus had a late onset. Conclusion Changes in flexibility and local polar contacts may be indicators of the NEU1 pathogenicity. Sialidosis type 1 can be divided into two subgroups according to the variant combinations, and patients with these two subtypes have different clinical characteristics.
{"title":"Clinical and structural characteristics of NEU1 variants causing sialidosis type 1.","authors":"Yingji Li, Yang Liu, Rongfei Wang, Ran Ao, Feng Xiang, Xu Zhang, Xiangqing Wang, Shengyuan Yu","doi":"10.14802/jmd.23145","DOIUrl":"https://doi.org/10.14802/jmd.23145","url":null,"abstract":"Purpose\u0000Sialidosis type 2 has variants that are both catalytically inactive (severe), while sialidosis type 1 has at least one catalytically active (mild) variant. This study aimed to discuss the structural changes associated with these variants in a newly reported family carrying NEU1 variants and explore the clinical characteristics of different combinations of variants in sialidosis type 1.\u0000\u0000\u0000Methods\u0000First, whole-exome sequencing and detailed clinical examination were performed on the family. Second, structural analysis, including energy, flexibility and polar contacts, was conducted for several NEU1 variants, and a sialidase activity assay was performed. Third, previous NEU1 variants were systematically reviewed, and the clinical characteristics of patients in the severe-mild and mild-mild groups with sialidosis type 1 were analyzed.\u0000\u0000\u0000Results\u0000We report a novel family with sialidosis type 1 and the compound heterozygous variants S182G and V143E. The newly identified V143E variant was predicted to be a mild variant through structural analysis and was confirmed by sialidase activity assay. The cherry-red spot was more prevalent in the severe-mild group, and ataxia was more common in the mild-mild group. Impaired cognition was found only in the severe-mild group. Moreover, patients with cherry-red spots and abnormal EEGs and VEPs had a relatively early age of onset, whereas patients with myoclonus had a late onset.\u0000\u0000\u0000Conclusion\u0000Changes in flexibility and local polar contacts may be indicators of the NEU1 pathogenicity. Sialidosis type 1 can be divided into two subgroups according to the variant combinations, and patients with these two subtypes have different clinical characteristics.","PeriodicalId":16372,"journal":{"name":"Journal of Movement Disorders","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140713225","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}
R. Bhidayasiri, Onanong Phokaewvarangkul, Thien Thien Lim, P. Pal, Hirohisa Watanabe, Jin Whan Cho, Hui-Fang Shang
{"title":"Neurological perspectives should be integrated into the management of tardive dyskinesia - expert opinion and proposed educational initiatives in Asia.","authors":"R. Bhidayasiri, Onanong Phokaewvarangkul, Thien Thien Lim, P. Pal, Hirohisa Watanabe, Jin Whan Cho, Hui-Fang Shang","doi":"10.14802/jmd.24068","DOIUrl":"https://doi.org/10.14802/jmd.24068","url":null,"abstract":"","PeriodicalId":16372,"journal":{"name":"Journal of Movement Disorders","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140714447","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}
Pavankumar Katragadda, V. Holla, N. Kamble, Ravi Yadav, P. Pal
{"title":"Haloperidol in managing DYT-TOR1A Dystonia: Unveiling a Dramatic Therapeutic Response.","authors":"Pavankumar Katragadda, V. Holla, N. Kamble, Ravi Yadav, P. Pal","doi":"10.14802/jmd.24029","DOIUrl":"https://doi.org/10.14802/jmd.24029","url":null,"abstract":"","PeriodicalId":16372,"journal":{"name":"Journal of Movement Disorders","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140722810","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}
T. Hatano, A. Okuzumi, Gen Matsumoto, Tsunemi Taiji, N. Hattori
Mutations in the SNCA gene, which encodes α-synuclein (α-syn), play a key role in the development of genetic Parkinson's disease (PD). α-Syn is a major component of Lewy bodies in PD and glial cytoplasmic inclusions in multiple system atrophy (MSA). Rapid eye movement sleep behavior disorder (RBD) patients often progress to PD, dementia with Lewy bodies (DLB), or MSA, collectively known as α-synucleinopathies. The loss of dopaminergic neurons with Lewy bodies precedes motor dysfunction in these diseases, but the mechanisms of neurodegeneration due to α-syn aggregation are poorly understood. Monitoring α-syn aggregation in vivo could serve as a diagnostic biomarker and help elucidate the pathogenesis, necessitating a simple and accurate detection method. Seed amplification assays (SAAs), such as real-time quaking-induced conversion (RT-QuIC) and protein misfolding cyclic amplification (PMCA), are used to detect small amounts of abnormally structured α-syn protofibrils, which are central to aggregation. These methods are promising for the early diagnosis of α-synucleinopathy. Differences in α-syn filament structures between α-synucleinopathies, observed through transmission electron microscopy and cryo-electron microscopy, suggest their role in the pathogenesis of neurodegeneration. SAAs may differentiate between subtypes of α-synucleinopathy and other diseases. Efforts are also being made to identify α-syn from blood using various methods. This review introduces body fluid α-syn biomarkers based on pathogenic α-syn seeds, which are expected to redefine α-synucleinopathy diagnosis and staging, improving clinical research accuracy and facilitating biomarker development.
{"title":"α-Synuclein: A Promising Biomarker for Parkinson's Disease and Related Disorders.","authors":"T. Hatano, A. Okuzumi, Gen Matsumoto, Tsunemi Taiji, N. Hattori","doi":"10.14802/jmd.24075","DOIUrl":"https://doi.org/10.14802/jmd.24075","url":null,"abstract":"Mutations in the SNCA gene, which encodes α-synuclein (α-syn), play a key role in the development of genetic Parkinson's disease (PD). α-Syn is a major component of Lewy bodies in PD and glial cytoplasmic inclusions in multiple system atrophy (MSA). Rapid eye movement sleep behavior disorder (RBD) patients often progress to PD, dementia with Lewy bodies (DLB), or MSA, collectively known as α-synucleinopathies. The loss of dopaminergic neurons with Lewy bodies precedes motor dysfunction in these diseases, but the mechanisms of neurodegeneration due to α-syn aggregation are poorly understood. Monitoring α-syn aggregation in vivo could serve as a diagnostic biomarker and help elucidate the pathogenesis, necessitating a simple and accurate detection method. Seed amplification assays (SAAs), such as real-time quaking-induced conversion (RT-QuIC) and protein misfolding cyclic amplification (PMCA), are used to detect small amounts of abnormally structured α-syn protofibrils, which are central to aggregation. These methods are promising for the early diagnosis of α-synucleinopathy. Differences in α-syn filament structures between α-synucleinopathies, observed through transmission electron microscopy and cryo-electron microscopy, suggest their role in the pathogenesis of neurodegeneration. SAAs may differentiate between subtypes of α-synucleinopathy and other diseases. Efforts are also being made to identify α-syn from blood using various methods. This review introduces body fluid α-syn biomarkers based on pathogenic α-syn seeds, which are expected to redefine α-synucleinopathy diagnosis and staging, improving clinical research accuracy and facilitating biomarker development.","PeriodicalId":16372,"journal":{"name":"Journal of Movement Disorders","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140727585","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}
Jinse Park, Eungseok Oh, Seong-Beom Koh, In-Uk Song, Tae-Beom Ahn, Sang Jin Kim, Sang-Myung Cheon, Yun Joong Kim, J. Cho, Hyeo-Il Ma, Mee-Young Park, Jong Sam Baik, Phil Hyu Lee, S. Chung, Jong-Min Kim, Han‐Joon Kim, Y. Sung, Do-Young Kwon, Jae-Hyeok Lee, Jee-Young Lee, Ji Sun Kim, J. Yun, Hee-Jin Kim, Jin Young Hong, Mi-Jung Kim, J. Youn, Ji Seon Kim, Hui-Jun Yang, Won Tae Yoon, Sooyeoun You, Kyum-Yil Kwon, Su-Yun Lee, Younsoo Kim, Hee-Tae Kim, Joong-Seok Kim, Ji-Young Kim
Objective The Scales for Outcomes in Parkinson's Disease-Cognition (SCOPA-Cog) was developed to screen for cognition in PD. In this study, we aimed to evaluate the validity and reliability of the Korean version of the SCOPA-cog. Methods We recruited 129 PD patients from 31 clinics with movement disorders in South Korea. The original version of the SCOPA-cognition was translated into Korean using the translation-retranslation method. The test-rest method with an intraclass correlation coefficient (ICC) and Cronbach's alpha coefficient were used to assess reliability. The Spearman's Rank correlation analysis with Montreal Cognitive Assessment-Korean version (MOCA-K) and Korean Mini-Mental State Examination (K-MMSE) were used to assess concurrent validity. Results The Cronbach's alpha coefficient was 0.797, and the ICC was 0.887. Spearman's rank correlation analysis showed a significant correlation with the K-MMSE and MOCA-K scores (r = 0.546 and r = 0.683, respectively). Conclusions Our results demonstrate that K-SCOPA-Cog exhibits good reliability and validity.
目的帕金森病认知结果量表（SCOPA-Cog）是为筛查帕金森病认知能力而开发的。本研究旨在评估韩国版 SCOPA-cog 的有效性和可靠性。采用翻译-再翻译法将原版 SCOPA-cognition 翻译成韩文。采用类内相关系数（ICC）和Cronbach's α系数的测试-静止法评估信度。结果 Cronbach's alpha 系数为 0.797，ICC 为 0.887，Spearman's rank correlation analysis with Montreal Cognitive Assessment-Korean version (MOCA-K) and Korean Mini-Mental State Examination (K-MMSE) were used to assess concurrent validity.Spearman's rank correlation analysis with Montreal Cognitive Assessment-Korean version (MOCA-K) and Korean Mini-Mental State Examination (K-MMSE) were used to assess concurrent validity.斯皮尔曼等级相关分析表明，K-SCOPA-Cog 与 K-MMSE 和 MOCA-K 分数之间存在显著的相关性（r = 0.546 和 r = 0.683）。
{"title":"Evaluating the validity and reliability of the Korean version of Scales for Outcomes in Parkinson's Disease-Cognition.","authors":"Jinse Park, Eungseok Oh, Seong-Beom Koh, In-Uk Song, Tae-Beom Ahn, Sang Jin Kim, Sang-Myung Cheon, Yun Joong Kim, J. Cho, Hyeo-Il Ma, Mee-Young Park, Jong Sam Baik, Phil Hyu Lee, S. Chung, Jong-Min Kim, Han‐Joon Kim, Y. Sung, Do-Young Kwon, Jae-Hyeok Lee, Jee-Young Lee, Ji Sun Kim, J. Yun, Hee-Jin Kim, Jin Young Hong, Mi-Jung Kim, J. Youn, Ji Seon Kim, Hui-Jun Yang, Won Tae Yoon, Sooyeoun You, Kyum-Yil Kwon, Su-Yun Lee, Younsoo Kim, Hee-Tae Kim, Joong-Seok Kim, Ji-Young Kim","doi":"10.14802/jmd.24061","DOIUrl":"https://doi.org/10.14802/jmd.24061","url":null,"abstract":"Objective\u0000The Scales for Outcomes in Parkinson's Disease-Cognition (SCOPA-Cog) was developed to screen for cognition in PD. In this study, we aimed to evaluate the validity and reliability of the Korean version of the SCOPA-cog.\u0000\u0000\u0000Methods\u0000We recruited 129 PD patients from 31 clinics with movement disorders in South Korea. The original version of the SCOPA-cognition was translated into Korean using the translation-retranslation method. The test-rest method with an intraclass correlation coefficient (ICC) and Cronbach's alpha coefficient were used to assess reliability. The Spearman's Rank correlation analysis with Montreal Cognitive Assessment-Korean version (MOCA-K) and Korean Mini-Mental State Examination (K-MMSE) were used to assess concurrent validity.\u0000\u0000\u0000Results\u0000The Cronbach's alpha coefficient was 0.797, and the ICC was 0.887. Spearman's rank correlation analysis showed a significant correlation with the K-MMSE and MOCA-K scores (r = 0.546 and r = 0.683, respectively).\u0000\u0000\u0000Conclusions\u0000Our results demonstrate that K-SCOPA-Cog exhibits good reliability and validity.","PeriodicalId":16372,"journal":{"name":"Journal of Movement Disorders","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140749708","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}
Pub Date : 2024-04-01Epub Date: 2024-01-15DOI: 10.14802/jmd.23249
Kazuya Yoshida
{"title":"Hemimasticatory Spasm Treated With Muscle Afferent Block Therapy and Occlusal Splint.","authors":"Kazuya Yoshida","doi":"10.14802/jmd.23249","DOIUrl":"10.14802/jmd.23249","url":null,"abstract":"","PeriodicalId":16372,"journal":{"name":"Journal of Movement Disorders","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11082605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139466804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01Epub Date: 2024-02-21DOI: 10.14802/jmd.24014
Marlies Gijs, Nynke Jorna, Nicole Datson, Chantal Beekman, Cira Dansokho, Alexander Weiss, David E J Linden, Mayke Oosterloo
Objective: Huntington's disease (HD) is an autosomal dominant, fully penetrant, neurodegenerative disease that most commonly affects middle-aged adults. HD is caused by a CAG repeat expansion in the HTT gene, resulting in the expression of mutant huntingtin (mHTT). Our aim was to detect and quantify mHTT in tear fluid, which, to our knowledge, has never been measured before.
Methods: We recruited 20 manifest and 13 premanifest HD gene expansion carriers, and 20 age-matched controls. All patients underwent detailed assessments, including the Unified Huntington's Disease Rating Scale (UHDRS) total motor score (TMS) and total functional capacity (TFC) score. Tear fluid was collected using paper Schirmer's strips. The level of tear mHTT was determined using single-molecule counting SMCxPRO technology.
Results: The average tear mHTT levels in manifest (67,223 ± 80,360 fM) and premanifest patients (55,561 ± 45,931 fM) were significantly higher than those in controls (1,622 ± 2,179 fM). We noted significant correlations between tear mHTT levels and CAG repeat length, "estimated years to diagnosis," disease burden score and UHDRS TMS and TFC. The receiver operating curve demonstrated an almost perfect score (area under the curve [AUC] = 0.9975) when comparing controls to manifest patients. Similarly, the AUC between controls and premanifest patients was 0.9846. The optimal cutoff value for distinguishing between controls and manifest patients was 4,544 fM, whereas it was 6,596 fM for distinguishing between controls and premanifest patients.
Conclusion: Tear mHTT has potential for early and noninvasive detection of alterations in HD patients and could be integrated into both clinical trials and clinical diagnostics.
{"title":"High Levels of Mutant Huntingtin Protein in Tear Fluid From Huntington's Disease Gene Expansion Carriers.","authors":"Marlies Gijs, Nynke Jorna, Nicole Datson, Chantal Beekman, Cira Dansokho, Alexander Weiss, David E J Linden, Mayke Oosterloo","doi":"10.14802/jmd.24014","DOIUrl":"10.14802/jmd.24014","url":null,"abstract":"<p><strong>Objective: </strong>Huntington's disease (HD) is an autosomal dominant, fully penetrant, neurodegenerative disease that most commonly affects middle-aged adults. HD is caused by a CAG repeat expansion in the HTT gene, resulting in the expression of mutant huntingtin (mHTT). Our aim was to detect and quantify mHTT in tear fluid, which, to our knowledge, has never been measured before.</p><p><strong>Methods: </strong>We recruited 20 manifest and 13 premanifest HD gene expansion carriers, and 20 age-matched controls. All patients underwent detailed assessments, including the Unified Huntington's Disease Rating Scale (UHDRS) total motor score (TMS) and total functional capacity (TFC) score. Tear fluid was collected using paper Schirmer's strips. The level of tear mHTT was determined using single-molecule counting SMCxPRO technology.</p><p><strong>Results: </strong>The average tear mHTT levels in manifest (67,223 ± 80,360 fM) and premanifest patients (55,561 ± 45,931 fM) were significantly higher than those in controls (1,622 ± 2,179 fM). We noted significant correlations between tear mHTT levels and CAG repeat length, \"estimated years to diagnosis,\" disease burden score and UHDRS TMS and TFC. The receiver operating curve demonstrated an almost perfect score (area under the curve [AUC] = 0.9975) when comparing controls to manifest patients. Similarly, the AUC between controls and premanifest patients was 0.9846. The optimal cutoff value for distinguishing between controls and manifest patients was 4,544 fM, whereas it was 6,596 fM for distinguishing between controls and premanifest patients.</p><p><strong>Conclusion: </strong>Tear mHTT has potential for early and noninvasive detection of alterations in HD patients and could be integrated into both clinical trials and clinical diagnostics.</p>","PeriodicalId":16372,"journal":{"name":"Journal of Movement Disorders","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11082600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139912783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01Epub Date: 2024-03-06DOI: 10.14802/jmd.23264
Ko-Eun Choi, Dong-Woo Ryu, Yoon-Sang Oh, Joong-Seok Kim
Objective: Hyperglycemia and diabetes mellitus have been identified as poor prognostic factors for motor and nonmotor outcomes in patients with Parkinson's disease (PD), although there is some controversy with this finding. In the present study, we investigated the effects of fasting plasma glucose (FPG) levels on longitudinal motor and cognitive outcomes in PD patients.
Methods: We included a total of 201 patients who were diagnosed with PD between January 2015 and January 2020. The patients were categorized based on FPG level into euglycemia (70 mg/dL < FPG < 100 mg/dL), intermediate glycemia (100 mg/dL ≤ FPG < 126 mg/dL), and hyperglycemia (FPG ≥ 126 mg/dL), and longitudinal FPG trajectories were analyzed using group-based trajectory modeling. Survival analysis was conducted to determine the time until motor outcome (Hoehn and Yahr stage ≥ 2) and the conversion from normal cognition to mild cognitive impairment.
Results: Among the patient cohort, 82 had euglycemia, 93 had intermediate glycemia, and 26 had hyperglycemia. Intermediate glycemia (hazard ratio 1.747, 95% confidence interval [CI] 1.083-2.816, p = 0.0221) and hyperglycemia (hazard ratio 3.864, 95% CI 1.996-7.481, p < 0.0001) were found to be significant predictors of worsening motor symptoms. However, neither intermediate glycemia (hazard ratio 1.183, 95% CI 0.697-2.009, p = 0.5339) nor hyperglycemia (hazard ratio 1.297, 95% CI 0.601-2.800, p = 0.5078) demonstrated associations with the longitudinal progression of cognitive impairment. Diabetes mellitus, defined by self-reported medical history, was not related to poor motor or cognitive impairment outcomes.
Conclusion: Our.
Results: suggest that both impaired glucose tolerance and hyperglycemia could be associated with motor progression in PD patients.
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