Lauren M Jackson, Bryan K Woodruff, C. Tremblay, Holly A. Shill, Thomas G. Beach, G. Serrano, Charles H Adler
BACKGROUND The G2019S leucine-rich repeat kinase 2 (LRRK2) gene mutation is an important and commonly found genetic determinant of Parkinson's disease (PD). The neuropathological findings associated with this mutation have thus far been varied but are most often associated with Lewy body (LB) pathology. OBJECTIVE Describe a case of clinical Parkinson's disease with levodopa responsiveness found to have LRRK2 mutations and the absence of Lewy bodies. METHOD We present an 89-year-old man with a 10-year history of slowly progressive parkinsonism suspected to be secondary to Parkinson's disease. RESULTS Neuropathological evaluation revealed nigral degeneration without Lewy bodies or Lewy neurites, but there were frequent tau-immunopositive neurites and astrocytes in the putamen and substantia nigra, neocortical glial tau positive astrocytes associated with aging-related tau astrogliopathy (ARTAG), as well as neurofibrillary tangles, beta amyloid plaques, and amyloid angiopathy typical of advanced Alzheimer's disease. G2019S LRRK2 homozygous mutations were found. CONCLUSION This case illustrates that levodopa-responsive clinical PD caused by G2019S LRRK2 mutations can occur without Lewy bodies.
{"title":"Parkinson's Disease Associated with G2019S LRRK2 Mutations without Lewy Body Pathology.","authors":"Lauren M Jackson, Bryan K Woodruff, C. Tremblay, Holly A. Shill, Thomas G. Beach, G. Serrano, Charles H Adler","doi":"10.1002/mdc3.14068","DOIUrl":"https://doi.org/10.1002/mdc3.14068","url":null,"abstract":"BACKGROUND\u0000The G2019S leucine-rich repeat kinase 2 (LRRK2) gene mutation is an important and commonly found genetic determinant of Parkinson's disease (PD). The neuropathological findings associated with this mutation have thus far been varied but are most often associated with Lewy body (LB) pathology.\u0000\u0000\u0000OBJECTIVE\u0000Describe a case of clinical Parkinson's disease with levodopa responsiveness found to have LRRK2 mutations and the absence of Lewy bodies.\u0000\u0000\u0000METHOD\u0000We present an 89-year-old man with a 10-year history of slowly progressive parkinsonism suspected to be secondary to Parkinson's disease.\u0000\u0000\u0000RESULTS\u0000Neuropathological evaluation revealed nigral degeneration without Lewy bodies or Lewy neurites, but there were frequent tau-immunopositive neurites and astrocytes in the putamen and substantia nigra, neocortical glial tau positive astrocytes associated with aging-related tau astrogliopathy (ARTAG), as well as neurofibrillary tangles, beta amyloid plaques, and amyloid angiopathy typical of advanced Alzheimer's disease. G2019S LRRK2 homozygous mutations were found.\u0000\u0000\u0000CONCLUSION\u0000This case illustrates that levodopa-responsive clinical PD caused by G2019S LRRK2 mutations can occur without Lewy bodies.","PeriodicalId":509823,"journal":{"name":"Movement Disorders Clinical Practice","volume":"59 38","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140970223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Fanella, Emanuele Cerulli Irelli, T. Accinni, F. Di Fabio, Carolina Putotto, Federica Pulvirenti, Francesco E Bellomi, C. Di Bonaventura, Giorgio Vivacqua
BACKGROUND 22q11.2 deletion syndrome (22q11.2DS) has been linked to an increased risk of early-onset Parkinson's disease. However, the pathophysiological mechanisms underlying parkinsonism remain poorly understood. OBJECTIVE The objective is to investigate salivary total α-synuclein levels in 22q11.2DS patients with and without parkinsonian motor signs. METHODS This cross-sectional study included 10 patients with 22q11.2DS with parkinsonism (Park+), ten 22q11.2DS patients without parkinsonism (Park-), and 10 age and sex-comparable healthy subjects (HS). Salivary and serum α-synuclein levels were measured using enzyme-linked immunosorbent assay. RESULTS Salivary total α-synuclein concentration was significantly lower in Park (+) patients than in Park (-) patients and HS (P = 0.007). In addition, salivary α-synuclein showed good accuracy in discriminating Park (+) from Park (-) patients (area under the curve = 0.86) and correlated with motor severity and cognitive impairment. CONCLUSION This exploratory study suggests that the parkinsonian phenotype of 22q11.2DS is associated with a reduced concentration of monomeric α-synuclein in biological fluids.
{"title":"Salivary α-Synuclein as a Candidate Biomarker of Parkinsonism in 22q11.2 Deletion Syndrome.","authors":"M. Fanella, Emanuele Cerulli Irelli, T. Accinni, F. Di Fabio, Carolina Putotto, Federica Pulvirenti, Francesco E Bellomi, C. Di Bonaventura, Giorgio Vivacqua","doi":"10.1002/mdc3.14046","DOIUrl":"https://doi.org/10.1002/mdc3.14046","url":null,"abstract":"BACKGROUND\u000022q11.2 deletion syndrome (22q11.2DS) has been linked to an increased risk of early-onset Parkinson's disease. However, the pathophysiological mechanisms underlying parkinsonism remain poorly understood.\u0000\u0000\u0000OBJECTIVE\u0000The objective is to investigate salivary total α-synuclein levels in 22q11.2DS patients with and without parkinsonian motor signs.\u0000\u0000\u0000METHODS\u0000This cross-sectional study included 10 patients with 22q11.2DS with parkinsonism (Park+), ten 22q11.2DS patients without parkinsonism (Park-), and 10 age and sex-comparable healthy subjects (HS). Salivary and serum α-synuclein levels were measured using enzyme-linked immunosorbent assay.\u0000\u0000\u0000RESULTS\u0000Salivary total α-synuclein concentration was significantly lower in Park (+) patients than in Park (-) patients and HS (P = 0.007). In addition, salivary α-synuclein showed good accuracy in discriminating Park (+) from Park (-) patients (area under the curve = 0.86) and correlated with motor severity and cognitive impairment.\u0000\u0000\u0000CONCLUSION\u0000This exploratory study suggests that the parkinsonian phenotype of 22q11.2DS is associated with a reduced concentration of monomeric α-synuclein in biological fluids.","PeriodicalId":509823,"journal":{"name":"Movement Disorders Clinical Practice","volume":"11 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140654428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BACKGROUND The term dystonic tremor is being increasingly used in neurological publications despite uncertainties about its meaning. We provide here a historical reconstruction from its original introduction in 1984 to help distinguish dystonia from essential tremor. METHODS A comprehensive Pubmed search of MeSH terms "dystonia", "tremor", and "essential tremor" provided the information base for reconstructing historical usage of the term "dystonic tremor". RESULTS Over the years, this expression was enriched of additional meanings and sided by companion descriptors, such as tremor associated with dystonia. Dystonic tremor has been considered characteristically coarse, jerky, irregular, directional and asymmetrical. These characteristics, however, are not included in the most recent definitions of tremor. The relationship between tremor and dystonia is not easy to untangle, as the two phenomena are often recognized in association. Tremor and dystonia experts have developed different visions of dystonic tremor that have been variably implemented. There are currently two independent consensus definitions, which are not coincident and imply different pathophysiological interpretations. CONCLUSIONS This historical reappraisal highlights that usage of the expression dystonic tremor has evolved over time to lose its original meaning. Notwithstanding inconsistencies of current definitions, its usage has steadily increased and it is time now to agree on an updated terminology.
{"title":"Dystonic Tremor: Time to Change.","authors":"S. Lalli, A. Albanese","doi":"10.1002/mdc3.14010","DOIUrl":"https://doi.org/10.1002/mdc3.14010","url":null,"abstract":"BACKGROUND\u0000The term dystonic tremor is being increasingly used in neurological publications despite uncertainties about its meaning. We provide here a historical reconstruction from its original introduction in 1984 to help distinguish dystonia from essential tremor.\u0000\u0000\u0000METHODS\u0000A comprehensive Pubmed search of MeSH terms \"dystonia\", \"tremor\", and \"essential tremor\" provided the information base for reconstructing historical usage of the term \"dystonic tremor\".\u0000\u0000\u0000RESULTS\u0000Over the years, this expression was enriched of additional meanings and sided by companion descriptors, such as tremor associated with dystonia. Dystonic tremor has been considered characteristically coarse, jerky, irregular, directional and asymmetrical. These characteristics, however, are not included in the most recent definitions of tremor. The relationship between tremor and dystonia is not easy to untangle, as the two phenomena are often recognized in association. Tremor and dystonia experts have developed different visions of dystonic tremor that have been variably implemented. There are currently two independent consensus definitions, which are not coincident and imply different pathophysiological interpretations.\u0000\u0000\u0000CONCLUSIONS\u0000This historical reappraisal highlights that usage of the expression dystonic tremor has evolved over time to lose its original meaning. Notwithstanding inconsistencies of current definitions, its usage has steadily increased and it is time now to agree on an updated terminology.","PeriodicalId":509823,"journal":{"name":"Movement Disorders Clinical Practice","volume":"41 17","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140662572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Fanciulli, Iva Stanković, Omer Avraham, Milica Jecmenica Lukic, A. Ezra, Fabian Leys, Georg Goebel, F. Krismer, Igor Petrović, M. Svetel, K. Seppi, Vladimir Kostić, Nir Giladi, W. Poewe, Gregor K Wenning, Tanya Gurevich
BACKGROUND A 4-item score based on ≥2 features out of orthostatic hypotension, overactive bladder, urinary retention and postural instability was previously shown to early distinguish the Parkinson-variant of multiple system atrophy (MSA-P) from Parkinson's disease (PD) with 78% sensitivity and 86% specificity. OBJECTIVES To replicate and improve the 4-item MSA-P score. METHODS We retrospectively studied 161 patients with early parkinsonism [ie, ≤2 years disease duration or no postural instability, aged 64 (57; 68) years, 44% females] and a diagnosis of clinically established MSA-P (n = 38) or PD (n = 123) after ≥24 months follow-up. RESULTS The 4-item MSA-P score had a 92% sensitivity and 78% specificity for a final MSA-P diagnosis. By including dopaminergic responsiveness and postural deformities into a 6-item score (range: 0-6), reaching ≥3 points at early disease identified MSA-P patients with 89% sensitivity and 98% specificity. CONCLUSIONS The 6-item MSA-P score is a cost-effective tool to pinpoint individuals with early-stage MSA-P.
{"title":"Early Screening for the Parkinson Variant of Multiple System Atrophy: A 6-Item Score.","authors":"A. Fanciulli, Iva Stanković, Omer Avraham, Milica Jecmenica Lukic, A. Ezra, Fabian Leys, Georg Goebel, F. Krismer, Igor Petrović, M. Svetel, K. Seppi, Vladimir Kostić, Nir Giladi, W. Poewe, Gregor K Wenning, Tanya Gurevich","doi":"10.1002/mdc3.14048","DOIUrl":"https://doi.org/10.1002/mdc3.14048","url":null,"abstract":"BACKGROUND\u0000A 4-item score based on ≥2 features out of orthostatic hypotension, overactive bladder, urinary retention and postural instability was previously shown to early distinguish the Parkinson-variant of multiple system atrophy (MSA-P) from Parkinson's disease (PD) with 78% sensitivity and 86% specificity.\u0000\u0000\u0000OBJECTIVES\u0000To replicate and improve the 4-item MSA-P score.\u0000\u0000\u0000METHODS\u0000We retrospectively studied 161 patients with early parkinsonism [ie, ≤2 years disease duration or no postural instability, aged 64 (57; 68) years, 44% females] and a diagnosis of clinically established MSA-P (n = 38) or PD (n = 123) after ≥24 months follow-up.\u0000\u0000\u0000RESULTS\u0000The 4-item MSA-P score had a 92% sensitivity and 78% specificity for a final MSA-P diagnosis. By including dopaminergic responsiveness and postural deformities into a 6-item score (range: 0-6), reaching ≥3 points at early disease identified MSA-P patients with 89% sensitivity and 98% specificity.\u0000\u0000\u0000CONCLUSIONS\u0000The 6-item MSA-P score is a cost-effective tool to pinpoint individuals with early-stage MSA-P.","PeriodicalId":509823,"journal":{"name":"Movement Disorders Clinical Practice","volume":"60 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140662458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Henri Gob, Astasia Abasia and the \"Swivel Chair Test\" for Functional Gait Disorders.","authors":"Michael S. Okun","doi":"10.1002/mdc3.14049","DOIUrl":"https://doi.org/10.1002/mdc3.14049","url":null,"abstract":"","PeriodicalId":509823,"journal":{"name":"Movement Disorders Clinical Practice","volume":"96 21","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140676498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Francesca Nardecchia, Simone Martinelli, L. Pollini, Vincenzo Leuzzi
{"title":"Reply to: Partially Levodopa-Responsive Parkinsonism in a Carrier of a Novel Pathogenic CLTC Variant.","authors":"Francesca Nardecchia, Simone Martinelli, L. Pollini, Vincenzo Leuzzi","doi":"10.1002/mdc3.14039","DOIUrl":"https://doi.org/10.1002/mdc3.14039","url":null,"abstract":"","PeriodicalId":509823,"journal":{"name":"Movement Disorders Clinical Practice","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140706182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Raquel Barbosa, Marcelo Mendonça, P. Bastos, P. Pita Lobo, A. Valadas, Leonor Correia Guedes, Joaquim J. Ferreira, Mário Miguel Rosa, Ricardo Matias, Miguel Coelho
BACKGROUND Quantitative 3D movement analysis using inertial measurement units (IMUs) allows for a more detailed characterization of motor patterns than clinical assessment alone. It is essential to discriminate between gait features that are responsive or unresponsive to current therapies to better understand the underlying pathophysiological basis and identify potential therapeutic strategies. OBJECTIVES This study aims to characterize the responsiveness and temporal evolution of different gait subcomponents in Parkinson's disease (PD) patients in their OFF and various ON states following levodopa administration, utilizing both wearable sensors and the gold-standard MDS-UPDRS motor part III. METHODS Seventeen PD patients were assessed while wearing a full-body set of 15 IMUs in their OFF state and at 20-minute intervals following the administration of a supra-threshold levodopa dose. Gait was reconstructed using a biomechanical model of the human body to quantify how each feature was modulated. Comparisons with non-PD control subjects were conducted in parallel. RESULTS Significant motor changes were observed in both the upper and lower limbs according to the MDS-UPDRS III, 40 minutes after levodopa intake. IMU-assisted 3D kinematics detected significant motor alterations as early as 20 minutes after levodopa administration, particularly in upper limbs metrics. Although all "pace-domain" gait features showed significant improvement in the Best-ON state, most rhythmicity, asymmetry, and variability features did not. CONCLUSION IMUs are capable of detecting motor alterations earlier and in a more comprehensive manner than the MDS-UPDRS III. The upper limbs respond more rapidly to levodopa, possibly reflecting distinct thresholds to levodopa across striatal regions.
{"title":"3D Kinematics Quantifies Gait Response to Levodopa earlier and to a more Comprehensive Extent than the MDS-Unified Parkinson's Disease Rating Scale in Patients with Motor Complications.","authors":"Raquel Barbosa, Marcelo Mendonça, P. Bastos, P. Pita Lobo, A. Valadas, Leonor Correia Guedes, Joaquim J. Ferreira, Mário Miguel Rosa, Ricardo Matias, Miguel Coelho","doi":"10.1002/mdc3.14016","DOIUrl":"https://doi.org/10.1002/mdc3.14016","url":null,"abstract":"BACKGROUND\u0000Quantitative 3D movement analysis using inertial measurement units (IMUs) allows for a more detailed characterization of motor patterns than clinical assessment alone. It is essential to discriminate between gait features that are responsive or unresponsive to current therapies to better understand the underlying pathophysiological basis and identify potential therapeutic strategies.\u0000\u0000\u0000OBJECTIVES\u0000This study aims to characterize the responsiveness and temporal evolution of different gait subcomponents in Parkinson's disease (PD) patients in their OFF and various ON states following levodopa administration, utilizing both wearable sensors and the gold-standard MDS-UPDRS motor part III.\u0000\u0000\u0000METHODS\u0000Seventeen PD patients were assessed while wearing a full-body set of 15 IMUs in their OFF state and at 20-minute intervals following the administration of a supra-threshold levodopa dose. Gait was reconstructed using a biomechanical model of the human body to quantify how each feature was modulated. Comparisons with non-PD control subjects were conducted in parallel.\u0000\u0000\u0000RESULTS\u0000Significant motor changes were observed in both the upper and lower limbs according to the MDS-UPDRS III, 40 minutes after levodopa intake. IMU-assisted 3D kinematics detected significant motor alterations as early as 20 minutes after levodopa administration, particularly in upper limbs metrics. Although all \"pace-domain\" gait features showed significant improvement in the Best-ON state, most rhythmicity, asymmetry, and variability features did not.\u0000\u0000\u0000CONCLUSION\u0000IMUs are capable of detecting motor alterations earlier and in a more comprehensive manner than the MDS-UPDRS III. The upper limbs respond more rapidly to levodopa, possibly reflecting distinct thresholds to levodopa across striatal regions.","PeriodicalId":509823,"journal":{"name":"Movement Disorders Clinical Practice","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140712140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
H. Morino, T. Kurashige, Y. Matsuda, M. Ono, N. Sahara, Tomohiro Miyasaka, Y. Soeda, Hitoshi Shimada, Yukari Yamazaki, Tetsuya Takahashi, Y. Izumi, Hidefumi Ito, Hirofumi Maruyama, Makoto Higuchi, Koji Arihiro, Tetsuya Suhara, Akihiko Takashima, Hideshi Kawakami
BACKGROUND MAPT is a causative gene in frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), a hereditary degenerative disease with various clinical manifestations, including progressive supranuclear palsy, corticobasal syndrome, Parkinson's disease, and frontotemporal dementia. OBJECTIVES To analyze genetically, biochemically, and pathologically multiple members of two families who exhibited various phenotypes of the disease. METHODS Genetic analysis included linkage analysis, homozygosity haplotyping, and exome sequencing. We conducted tau protein microtubule polymerization assay, heparin-induced tau aggregation, and western blotting with brain lysate from an autopsy case. We also evaluated abnormal tau aggregation by using anti-tau antibody and PM-PBB3. RESULTS We identified a variant, c.896_897insACA, p.K298_H299insQ, in the MAPT gene of affected patients. Similar to previous reports, most patients presented with atypical parkinsonism. Biochemical analysis revealed that the mutant tau protein had a reduced ability to polymerize microtubules and formed abnormal fibrous aggregates. Pathological study revealed frontotemporal lobe atrophy, midbrain atrophy, depigmentation of the substantia nigra, and four-repeat tau-positive inclusions in the hippocampus, brainstem, and spinal cord neurons. The inclusion bodies also stained positively with PM-PBB3. CONCLUSIONS This study confirmed that the insACA mutation caused FTDP-17. The affected patients showed symptoms resembling Parkinson's disease initially and symptoms of progressive supranuclear palsy later. Despite the initial clinical diagnosis of frontotemporal dementia in the autopsy case, the spread of lesions could explain the process of progressive supranuclear palsy. The study of more cases in the future will help clarify the common pathogenesis of MAPT mutations or specific pathogeneses of each mutation.
背景MAPT是额颞叶痴呆伴帕金森病的致病基因，与第17号染色体（FTDP-17）相连，这是一种遗传性退行性疾病，有多种临床表现，包括进行性核上性麻痹、皮质基底综合征、帕金森病和额颞叶痴呆。方法遗传学分析包括连锁分析、同源性单倍型分析和外显子组测序。我们对一个尸检病例的脑裂解液进行了 tau 蛋白微管聚合试验、肝素诱导的 tau 聚合试验和 western 印迹试验。我们还使用抗 tau 抗体和 PM-PBB3 评估了 tau 的异常聚集。结果 我们在受影响患者的 MAPT 基因中发现了一个变异体 c.896_897insACA，p.K298_H299insQ。与之前的报道相似，大多数患者表现为非典型帕金森病。生化分析表明，突变的 tau 蛋白聚合微管的能力减弱，并形成异常的纤维状聚集体。病理研究显示，患者的额颞叶萎缩、中脑萎缩、黑质色素沉着，海马、脑干和脊髓神经元中出现四重复tau阳性包涵体。结论这项研究证实，insACA 基因突变导致了 FTDP-17。患者最初表现出类似帕金森病的症状，随后出现进行性核上性麻痹的症状。尽管尸检病例最初的临床诊断是额颞叶痴呆，但病变的扩散可以解释进行性核上麻痹的过程。未来对更多病例的研究将有助于明确MAPT突变的共同发病机制或每种突变的特定发病机制。
{"title":"Clinical and Pathological Features of FTDP-17 with MAPT p.K298_H299insQ Mutation.","authors":"H. Morino, T. Kurashige, Y. Matsuda, M. Ono, N. Sahara, Tomohiro Miyasaka, Y. Soeda, Hitoshi Shimada, Yukari Yamazaki, Tetsuya Takahashi, Y. Izumi, Hidefumi Ito, Hirofumi Maruyama, Makoto Higuchi, Koji Arihiro, Tetsuya Suhara, Akihiko Takashima, Hideshi Kawakami","doi":"10.1002/mdc3.14042","DOIUrl":"https://doi.org/10.1002/mdc3.14042","url":null,"abstract":"BACKGROUND\u0000MAPT is a causative gene in frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), a hereditary degenerative disease with various clinical manifestations, including progressive supranuclear palsy, corticobasal syndrome, Parkinson's disease, and frontotemporal dementia.\u0000\u0000\u0000OBJECTIVES\u0000To analyze genetically, biochemically, and pathologically multiple members of two families who exhibited various phenotypes of the disease.\u0000\u0000\u0000METHODS\u0000Genetic analysis included linkage analysis, homozygosity haplotyping, and exome sequencing. We conducted tau protein microtubule polymerization assay, heparin-induced tau aggregation, and western blotting with brain lysate from an autopsy case. We also evaluated abnormal tau aggregation by using anti-tau antibody and PM-PBB3.\u0000\u0000\u0000RESULTS\u0000We identified a variant, c.896_897insACA, p.K298_H299insQ, in the MAPT gene of affected patients. Similar to previous reports, most patients presented with atypical parkinsonism. Biochemical analysis revealed that the mutant tau protein had a reduced ability to polymerize microtubules and formed abnormal fibrous aggregates. Pathological study revealed frontotemporal lobe atrophy, midbrain atrophy, depigmentation of the substantia nigra, and four-repeat tau-positive inclusions in the hippocampus, brainstem, and spinal cord neurons. The inclusion bodies also stained positively with PM-PBB3.\u0000\u0000\u0000CONCLUSIONS\u0000This study confirmed that the insACA mutation caused FTDP-17. The affected patients showed symptoms resembling Parkinson's disease initially and symptoms of progressive supranuclear palsy later. Despite the initial clinical diagnosis of frontotemporal dementia in the autopsy case, the spread of lesions could explain the process of progressive supranuclear palsy. The study of more cases in the future will help clarify the common pathogenesis of MAPT mutations or specific pathogeneses of each mutation.","PeriodicalId":509823,"journal":{"name":"Movement Disorders Clinical Practice","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140714900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Seungmin Lee, Han-Joon Kim, Bora Jin, Seoyeon Kim, Ho-Hyeon Jeon, K. Woo, J. Shin, Ho-Sung Myeong, Sun Ha Paek, B. Jeon
{"title":"Emergency Department Visits in Patients with Parkinson's Disease with Deep Brain Stimulation.","authors":"Seungmin Lee, Han-Joon Kim, Bora Jin, Seoyeon Kim, Ho-Hyeon Jeon, K. Woo, J. Shin, Ho-Sung Myeong, Sun Ha Paek, B. Jeon","doi":"10.1002/mdc3.14047","DOIUrl":"https://doi.org/10.1002/mdc3.14047","url":null,"abstract":"","PeriodicalId":509823,"journal":{"name":"Movement Disorders Clinical Practice","volume":"36 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140725000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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