Review
Medicine, Research & Experimental
Fan Shuen Tseng, Joel Qi Xuan Foo, Aaron Shengting Mai, Eng-King Tan
Summary: Multiple system atrophy (MSA) is a neurodegenerative disease characterized by dysautonomia, parkinsonism, cerebellar dysfunction, and corticospinal degeneration. The underlying mechanism involves aberrant alpha-synuclein deposition, mitochondrial dysfunction, oxidative stress, and neuroinflammation. There is also a possible genetic component that contributes to the risk and progression of MSA. Understanding the genetic factors and pathways involved in MSA can provide insights into potential therapeutic targets.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Neurosciences
Takashi Matsukawa, Kristine Joyce L. Porto, Jun Mitsui, Ayaka Chikada, Hiroyuki Ishiura, Yuji Takahashi, Fumiko Kusunoki Nakamoto, Tomonari Seki, Yasushi Shiio, Tatsushi Toda, Shoji Tsuji
Summary: This study identified multiple families with MSA and PD in first-degree relatives, suggesting a possible common genetic basis between the two diseases. Although variants in COQ2 and GBA were found in some patients, further research is needed to explore unidentified genetic risk factors shared by MSA and PD.
Article
Clinical Neurology
Marina Picillo, Sara Scannapieco, Alessandro Iavarone, Monia Ginevrino, Enza Maria Valente, Paolo Barone
Summary: This study reports for the first time a patient diagnosed with Posterior Cortical Atrophy carrying the common GBA gene variant N370S, which showed significantly reduced glucocerebrosidase activity, providing further evidence for the pathogenicity of this disease.
Article
Neurosciences
Anna I. Wernick, Ronald L. Walton, Alexandra I. Soto-Beasley, Shunsuke Koga, Yingxue Ren, Michael G. Heckman, Lukasz M. Milanowski, Rebecca R. Valentino, Naveen Kondru, Ryan J. Uitti, William P. Cheshire, Zbigniew K. Wszolek, Dennis W. Dickson, Owen A. Ross
Summary: A recent study found no significant association between coding variants in ELOVL7 and the risk of MSA, based on sequencing data from MSA cases, PD cases, and healthy controls.
NEUROSCIENCE LETTERS
(2021)
Article
Neurosciences
Marco Toffoli, Harneek Chohan, Stephen Mullin, Aaron Jesuthasan, Selen Yalkic, Sofia Koletsi, Elisa Menozzi, Soraya Rahall, Naomi Limbachiya, Nadine Loefflad, Abigail Higgins, Jonathan Bestwick, Sara Lucas-Del-Pozo, Federico Fierli, Audrey Farbos, Roxana Mezabrovschi, Chiao Lee-Yin, Anette Schrag, David Moreno-Martinez, Derralynn Hughes, Alastair Noyce, Kevin Colclough, Aaron R. Jeffries, Christos Proukakis, Anthony H. V. Schapira
Summary: This study compared the motor and non-motor phenotypes of GBA1 carriers and non-carriers. The results showed that GBA1-positive PD patients had worse performance in visual cognitive tasks and olfaction compared to GBA1-negative PD patients. However, the study did not replicate previous findings of more frequent prodromal PD signs in non-affected GBA1 carriers.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Clinical Neurology
Anna I. Wernick, Ronald L. Walton, Alexandra I. Soto-Beasley, Shunsuke Koga, Michael G. Heckman, Rebecca R. Valentino, Lukasz M. Milanowski, Dorota Hoffman-Zacharska, Dariusz Koziorowski, Anhar Hassan, Ryan J. Uitti, William P. Cheshire, Wolfgang Singer, Zbigniew K. Wszolek, Dennis W. Dickson, Phillip A. Low, Owen A. Ross
Summary: The occurrence of longer TBP CAG/CAA repeat alleles (>38 repeats) is significantly associated with an increased risk of multiple system atrophy, suggesting a possible genetic overlap between multiple system atrophy and SCA17.
CLINICAL AUTONOMIC RESEARCH
(2021)
Article
Clinical Neurology
Sitki Cem Parlar, Francis P. P. Grenn, Jonggeol Jeffrey Kim, Cornelis Baluwendraat, Ziv Gan-Or
Summary: This review aims to generate and share a comprehensive database for GBA1 variants reported in Parkinson's disease (PD) to support future research and clinical trials. A total of 371 GBA1 variants in PD were found and a browser containing up-to-date information on these variants was created. The classification and browser presented in this work will inform and support basic, translational, and clinical research on GBA1-PD.
MOVEMENT DISORDERS
(2023)
Review
Immunology
Marta Lenska-Mieciek, Natalia Madetko-Alster, Piotr Alster, Leszek Krolicki, Urszula Fiszer, Dariusz Koziorowski
Summary: Misfolding and aggregation of proteins are major pathological features of several neurodegenerative diseases. These diseases include neurodegenerative diseases with atypical Parkinsonism and the accumulation of insoluble fibrillary alpha-synuclein or hyperphosphorylated tau protein fragments. In the absence of available therapies to slow or halt disease progression, targeting the inflammatory process shows promise. Inflammatory biomarkers may also aid in the differential diagnosis of Parkinsonian syndromes.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Neurosciences
Xuewen Xiao, Qijie Yang, Yafei Wen, Bin Jiao, Xinxin Liao, Yafang Zhou, Ling Weng, Hui Liu, Tianyan Xu, Yuan Zhu, Lina Guo, Lu Zhou, Xin Wang, Xixi Liu, Xiangyun Bi, Yingzi Liu, Sizhe Zhang, Weiwei Zhang, Jinchen Li, Beisha Tang, Lu Shen
Summary: This study fills the gap in PSP genetic research in East Asian populations. The results show that pathogenic variants in MAPT are uncommon in PSP patients, while the GBA gene may increase the risk of PSP.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Neurosciences
Natalia Del Campo, Owen Phillips, Francoise Ory-Magne, Christine Brefel-Courbon, Monique Galitzky, Claire Thalamas, Katherine L. Narr, Shantanu Joshi, Manpreet K. Singh, Patrice Peran, Anne Pavy-LeTraon, Olivier Rascol
Summary: Multiple system atrophy (MSA) is a rare neurodegenerative disorder characterized by widespread accumulation of alpha-synuclein, primarily in oligodendrocytes. Whole brain deep and superficial white matter diffusivity abnormalities were observed in MSA patients but not in Parkinson's disease (PD) patients. These abnormalities were associated with motor and cognitive functions in MSA patients.
HUMAN BRAIN MAPPING
(2021)
Article
Clinical Neurology
Viorica Chelban, Elham Nikram, Alexandra Perez-Soriano, Carlo Wilke, Alexandra Foubert-Samier, Nirosen Vijiaratnam, Tong Guo, Edwin Jabbari, Simisola Olufodun, Mariel Gonzalez, Konstantin Senkevich, Brice Laurens, Patrice Peran, Olivier Rascol, Anne Pavy Le Traon, Emily G. Todd, Alyssa A. Costantini, Sondos Alikhwan, Ambreen Tariq, Bai Lin Ng, Esteban Munoz, Celia Painous, Yaroslau Compta, Carme Junque, Barbara Segura, Kristina Zhelcheska, Henny Wellington, Ludger Schoels, Zane Jaunmuktane, Christopher Kobylecki, Alistair Church, Michele T. M. Hu, James B. Rowe, P. Nigel Leigh, Luke Massey, David J. Burn, Nicola Pavese, Tom Foltynie, Sofya Pchelina, Nicholas Wood, Amanda J. Heslegrave, Henrik Zetterberg, Martina Bocchetta, Jonathan D. Rohrer, Maria J. Marti, Matthis Synofzik, Huw R. Morris, Wassilios G. Meissner, Henry Houlden
Summary: In this study, it was found that plasma neurofilament light chain levels correlate with clinical disease severity, progression, and prognosis in multiple system atrophy, providing valuable information for patient stratification and treatment response monitoring in future trials. The use of neurofilament light chain as a biomarker in multiple system atrophy holds promise for improving trial outcomes and streamlining participant recruitment. Further research is warranted to fully understand the potential of neurofilament light chain in multiple system atrophy management.
Article
Clinical Neurology
Marco Toffoli, Abigail Higgins, Chiao Lee, Sofia Koletsi, Xiao Chen, Michael Eberle, Fritz J. Sedlazeck, Stephen Mullin, Christos Proukakis, Anthony H. Schapira
Summary: Through studying a large cohort, we found that GBA haplotypes do not affect age at diagnosis of PD.
MOVEMENT DISORDERS
(2021)
Article
Clinical Neurology
Florian Krismer, Patrice Peran, Vincent Beliveau, Klaus Seppi, Germain Arribarat, Anne Pavy-Le Traon, Wassilios G. Meissner, Alexandra Foubert-Samier, Margherita Fabbri, Michael M. Schocke, Mark Forrest Gordon, Gregor K. Wenning, Werner Poewe, Olivier Rascol, Christoph Scherfler
Summary: This study aimed to determine the rates of brain atrophy progression in vivo in patients with multiple system atrophy (MSA). The results showed that MSA patients exhibited significant brain volume loss over 12 months, with the cerebellum, pons, and putamen being the most sensitive brain regions.
MOVEMENT DISORDERS
(2023)
Review
Biochemistry & Molecular Biology
Kurt A. Jellinger, Gregor K. Wenning, Nadia Stefanova
Summary: Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disease with a complex clinical presentation. It shares molecular similarities with Parkinson's disease but presents unique pathological features. The debate over whether it should be classified as a prion disease or its potential human transmission remains unresolved.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Clinical Neurology
Yi-Chien Yang, Fang-Tzu Chang, Jui-Cheng Chen, Chon-Haw Tsai, Fu-Yu Lin, Ming-Kuei Lu
Summary: The study investigated motor cortical dysfunction in patients with multiple system atrophy using Bereitschaftspotential (BP) recordings, finding significantly reduced late BP amplitudes in these patients. The dysfunction in voluntary movement preparation and activation can be practically evaluated using late BP, representing the cerebello-dentato-thalamo-cortical pathway.
FRONTIERS IN NEUROLOGY
(2021)
Article
Clinical Neurology
Marina Buciuc, Shunsuke Koga, Nha Trang Thu Pham, Joseph R. Duffy, David S. Knopman, Farwa Ali, Bradley F. Boeve, Jon Graff-Radford, Hugo Botha, Val J. Lowe, Aivi Nguyen, Ross R. Reichard, Dennis W. Dickson, Ronald C. Petersen, Jennifer L. Whitwell, Keith A. Josephs
Summary: Globular glial tauopathy (GGT) is commonly associated with frontotemporal dementia syndromes, but little is known about its clinical and imaging characteristics. This study compared GGT with other non-globular glial 4-repeat tauopathies (N4GT) and found that GGT patients were more likely to be female and to have lower motor neuron involvement. Additionally, GGT patients exhibited asymmetric frontotemporal atrophy and preserved midbrain volume.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Jaroslaw Dulski, Shunsuke Koga, Dennis W. Dickson, Zbigniew K. Wszolek
Summary: This paper reports a family with typical clinical, radiological, and pathological features of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), but negative for CSF1R, AARS1, and AARS2 mutations. It highlights the importance of further investigation into a new entity within the ALSP disease spectrum in order to identify the genetic cause and implement effective treatment.
MOVEMENT DISORDERS CLINICAL PRACTICE
(2023)
Article
Clinical Neurology
Nicholas B. B. Martin, Shunsuke Koga, Brian S. S. Appleby, Hiroaki Sekiya, Dennis W. Dickson
Summary: Two cases of patients who were misdiagnosed with multiple system atrophy (MSA) actually had Creutzfeldt-Jakob disease (CJD), as confirmed by neuropathological findings. This suggests that when the disease progresses rapidly or the clinical course is atypical, even if clinical features suggest MSA, the possibility of CJD should also be considered.
MOVEMENT DISORDERS CLINICAL PRACTICE
(2023)
Letter
Engineering, Biomedical
Shunsuke Koga
ANNALS OF BIOMEDICAL ENGINEERING
(2023)
Article
Clinical Neurology
Jon-Anders Tunold, Manuela M. X. Tan, Shunsuke Koga, Hanneke Geut, Annemieke J. M. Rozemuller, Rebecca Valentino, Hiroaki Sekiya, Nicholas B. Martin, Michael G. Heckman, Jose Bras, Rita Guerreiro, Dennis W. Dickson, Mathias Toft, Wilma D. J. van de Berg, Owen A. Ross, Lasse Pihlstrom
Summary: The genetic risk of Alzheimer's disease is associated with amyloid and tau accumulation, while Lewy body pathology is increased with a higher burden of Parkinson's disease risk variants affecting the lysosomal pathway.
Article
Clinical Neurology
Xu Hou, Taylor Hsuan-Yu Chen, Shunsuke Koga, Jenny M. Bredenberg, Ayman H. Faroqi, Marion Delenclos, Guojun Bu, Zbigniew K. Wszolek, Jonathan A. Carr, Owen A. Ross, Pamela J. McLean, Melissa E. Murray, Dennis W. Dickson, Fabienne C. Fiesel, Wolfdieter Springer
Summary: Alpha-synuclein (alpha syn) aggregates are pathological features of neurodegenerative diseases, and the deposition of alpha syn may be influenced by mitochondrial dysfunction and impairments of the autophagic-lysosomal system. This study investigated the potential connection between alpha syn and the PINK1-PRKN-mediated mitochondrial autophagy pathway. The findings suggest that phosphorylated ubiquitin (pS65-Ub) may serve as a biomarker and potential therapeutic target for Lewy body disease.
Article
Clinical Neurology
William P. P. Cheshire, Shunsuke Koga, Philip W. W. Tipton, Hiroaki Sekiya, Owen A. A. Ross, Ryan J. J. Uitti, Keith A. A. Josephs, Dennis W. W. Dickson
Summary: The aim of this study was to assess the relationship between multiple system atrophy (MSA) and cancer. The study found no significant clinical association between MSA and breast cancer or other cancers.
CLINICAL AUTONOMIC RESEARCH
(2023)
Letter
Clinical Neurology
Shunsuke Koga, Aya Murakami, Nicholas B. Martin, Dennis W. Dickson
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2023)
Article
Clinical Neurology
Nicholas B. B. Martin, Hiroaki Sekiya, Minji Kim, Dennis W. W. Dickson, Shunsuke Koga
Summary: The study evaluated the value of a questionnaire in differentiating between parkinsonian disorders. The information from the questionnaire correlated with core clinical features and predicted neuropathologic diagnosis. This highlights the usefulness of the questionnaire in clinicopathological studies.
MOVEMENT DISORDERS CLINICAL PRACTICE
(2023)
Article
Clinical Neurology
Jaroslaw Dulski, Shunsuke Koga, Pawel P. Liberski, Emilia J. J. Sitek, Ankur A. A. Butala, Jaroslaw Slawek, Dennis W. W. Dickson, Zbigniew K. K. Wszolek
Summary: This paper presents the first clinicopathological report of Perry disease (PS) caused by a novel DCTN1 mutation outside the CAP-Gly domain. The clinical and pathological features of the new variant carrier are compared with other reported cases.
MOVEMENT DISORDERS CLINICAL PRACTICE
(2023)
Article
Clinical Neurology
Shunsuke Koga, Nicholas B. Martin, Dennis W. Dickson
Summary: This study examines the effectiveness of large language models (LLMs), such as ChatGPT and Google Bard, in predicting neuropathologic diagnoses based on clinical summaries. 25 cases of neurodegenerative disorders were analyzed, and the LLMs provided multiple pathologic diagnoses and their rationales, which were compared to the clinical diagnoses made by physicians. The results show that ChatGPT-3.5, ChatGPT-4, and Google Bard correctly made primary diagnoses in 32%, 52%, and 40% of cases, respectively, and included correct diagnoses in 76%, 84%, and 76% of cases, respectively. These findings suggest that AI tools like ChatGPT can enhance discussions in neuropathology.
Correction
Neurosciences
Shunsuke Koga, Aya Murakami, Alexandra I. Soto-Beasley, Ronald L. Walton, Matthew C. Baker, Monica Castanedes-Casey, Keith A. Josephs, Owen A. Ross, Dennis W. Dickson
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Article
Neurosciences
Shunsuke Koga, Aya Murakami, Alexandra I. Soto-Beasley, Ronald L. Walton, Matthew C. Baker, Monica Castanedes-Casey, Keith A. Josephs, Owen A. Ross, Dennis W. Dickson
Summary: Frontotemporal lobar degeneration (FTLD) is a group of disorders characterized by degeneration of the frontal and temporal lobes, leading to decline in language, behavior, and motor function. In this report, a mixed neurodegenerative disease with features of diffuse argyrophilic grain disease (AGD), TDP-43 proteinopathy, and neuronal intermediate filament inclusion disease was observed in an 87-year-old woman. This case emphasizes the importance of considering multiple proteinopathies in the diagnosis of neurodegenerative diseases.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Article
Clinical Neurology
Arenn F. Carlos, Hiroaki Sekiya, Shunsuke Koga, Rodolfo G. Gatto, Monica Castanedes Casey, Nha Trang Thu Pham, Irene Sintini, Mary M. Machulda, Clifford R. Jack, Val J. Lowe, Jennifer L. Whitwell, Leonard Petrucelli, R. Ross Reichard, Ronald C. Petersen, Dennis W. Dickson, Keith A. Josephs
Summary: We have identified a novel TDP-43 pathology with star-shaped morphology associated with superaging, with a homogeneous clinicopathologic picture, possibly representing a novel, true aging-related TDP-43 pathology.
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2023)
Meeting Abstract
Clinical Neurology
Shunsuke Koga, Minji Kim, Hiroaki Sekiya, Nicholas Martin, Monica Castanedes-Casey, Gary Yao, Dennis Dickson, Tae Hyun Hwang
Article
Clinical Neurology
Jun-Pyo Hong, Hanim Kwon, Euyhyun Park, Sun-Uk Lee, Chan-Nyoung Lee, Byung-Jo Kim, Ji-Soo Kim, Kun-Woo Park
Summary: In patients with mild-to-moderate PD, vestibular function assessed by video head-impulse tests appears relatively preserved and has minimal impact on the risk of falls. Risk of postural instability is associated with the severity of clinical symptoms in PD.
PARKINSONISM & RELATED DISORDERS
(2024)
Article
Clinical Neurology
Yaqin Xiang, XiuRong Huang, Qian Xu, Zhenhua Liu, Yase Chen, Qiying Sun, Junling Wang, Hong Jiang, Lu Shen, Xinxiang Yan, Beisha Tang, Jifeng Guo
Summary: Using the novel data-driven method DEBM, this study determined the sequence of several common biomarker changes in Parkinson's disease (PD). The left putamen was found to be the earliest biomarker to become abnormal, followed by the right putamen, CSF alpha-synuclein, right caudate, left caudate, and serum NfL. The estimated disease stages showed significant differences between PD and healthy controls, and achieved a high accuracy for distinguishing PD from HC.
PARKINSONISM & RELATED DISORDERS
(2024)
Article
Clinical Neurology
Yan Li, David J. McLernon, Carl E. Counsell, Angus D. Macleod
Summary: This study aimed to investigate the incidence and risk factors for institutionalisation in Parkinson's disease (PD) and atypical parkinsonism (AP). The study found that institutionalisation was more frequent in AP compared to PD and controls. Age, poorer cognition, and more-severe parkinsonian impairment were independent predictors of institutionalisation.
PARKINSONISM & RELATED DISORDERS
(2024)