Article
Clinical Neurology
Xavier Ayrignac, Clarisse Carra-Dalliere, Pekes Codjia, Kevin Mouzat, Giovanni Castelnovo, Emmanuel Ellie, Frederique Etcharry-Bouyx, Serge Belliard, Cecilia Marelli, Florence Portet, Isabelle Le Ber, Francoise Durand-Dubief, Guillaume Mathey, Bruno Stankoff, Imen Dorboz, Severine Drunat, Odile Boespflug-Tanguy, Nicolas Menjot de Champfleur, Serge Lumbroso, Fanny Mochel, Pierre Labauge
Summary: The diagnostic criteria for ALSP have limited sensitivity and modest specificity overall, suggesting the need for a comprehensive approach including magnetic resonance imaging pattern-based analysis and genetic testing like white matter gene panel or whole exome sequencing in patients suspected of genetic leukoencephalopathy.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Review
Genetics & Heredity
Long Guo, Shiro Ikegawa
Summary: Mutations in CSF1R can cause various monogenic disorders, with the new disease BANDDOS showing a more severe and diverse phenotype, including brain abnormalities and skeletal dysplasia. A dose-dependent model is proposed to explain the complex genotype-phenotype association.
JOURNAL OF HUMAN GENETICS
(2021)
Review
Clinical Neurology
Spyros Papapetropoulos, Angela Pontius, Elizabeth Finger, Virginija Karrenbauer, David S. Lynch, Matthew Brennan, Samantha Zappia, Wolfgang Koehler, Ludger Schoels, Stefanie N. Hayer, Takuya Konno, Takeshi Ikeuchi, Troy Lund, Jennifer Orthmann-Murphy, Florian Eichler, Zbigniew K. Wszolek
Summary: This paper comprehensively reviews the various aspects of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), including genetics, neuropathology, imaging findings, prevalence, clinical course, diagnosis/clinical evaluation, potential biomarkers, and current and proposed treatments. It also discusses potential efficacy endpoints for future clinical trials and the burden of the disease on patients and caregivers. The information in this paper lays a foundation for the development of therapeutic agents for ALSP and the design of future clinical trials with meaningful endpoints.
FRONTIERS IN NEUROLOGY
(2022)
Review
Clinical Neurology
Karthik Muthusamy, Ajith Sivadasan, Luke Dixon, Sniya Sudhakar, Maya Thomas, Sumita Danda, Zbigniew K. Wszolek, Klaas Wierenga, Radhika Dhamija, Ralitza Gavrilova
Summary: Adult-onset leukodystrophies, although individually rare, are not uncommon. They can be easily misdiagnosed due to the overlap with common acquired disorders and the challenges posed by non-specific white matter changes. A comprehensive evaluation and genetic confirmation are important for early diagnosis and treatment. In this review, we aim to provide a useful approach to adult-onset leukodystrophies, discussing their presentations, neuroimaging findings, treatment options, and diagnostic algorithms.
FRONTIERS IN NEUROLOGY
(2023)
Review
Biochemistry & Molecular Biology
Isidro Ferrer
Summary: This article introduces several genetic disorders that cause damage to cerebral white matter. The naming of these diseases can be confusing, with different terms being used to designate the same disease. CSF1R mutations cause CSF-1R-related leukoencephalopathy (CRP), while AARS2 mutations lead to a mitochondrial disease called ALSP. PLOSL is a systemic disease caused by mutations in the genes TYROBP or TREM2.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Min Chu, Dong-Xin Wang, Yue Cui, Yu Kong, Li Liu, Ke-Xin Xie, Tian-Xinyu Xia, Jing Zhang, Ran Gao, Ai-Hong Zhou, Chao-Dong Wang, Li-Yong Wu
Summary: This study conducted whole-exome sequencing on nine Chinese patients with ALSP, identifying seven CSF1R mutations, including four known and three novel mutations. These findings expand the understanding of the mutational spectrum of ALSP and provide a basis for future research on etiologic factors and potential management strategies.
ANNALS OF TRANSLATIONAL MEDICINE
(2021)
Article
Clinical Neurology
Chengyuan Song, Fengjuan Wu, Yiming Liu, Xinwei Wu, Yuying Zhao
Summary: This article reports two cases of late-onset hereditary diffuse leukoencephalopathy with spheroids (HDLS) in unrelated families. MRI findings showed persistent patchy hyperintensities, and genetic testing identified variants in the CSF1R gene. Skin biopsy revealed characteristic swelling of unmyelinated axons (spheroids).
Letter
Clinical Neurology
Luca Marsili, Marcelo A. Kauffman, Diandra Rufin Florat, Amir Zaidi, Vanesa Botsford, Jennifer Sharma, Elizabeth G. Keeling, Joseph P. Broderick, Saulius Sumanas, Alberto J. Espay
Summary: This article describes an elderly woman who meets the criteria for vascular parkinsonism/dementia associated with a likely pathogenic COL22A1 gene variant. The findings are supported by functional experiments in a zebrafish model. The authors suggest that white matter hyperintensities may not represent small-vessel ischemic disease and propose that COL22A1 may be included among the adult-onset leukoencephalopathies mislabeled as vascular parkinsonism.
PARKINSONISM & RELATED DISORDERS
(2023)
Article
Clinical Neurology
Qin Du, Minjin Wang, Hongyu Zhou
Summary: A novel missense mutation, p.L755P, in the CSF1R gene was identified in a Chinese family with autosomal-dominant HDLS, expanding the genetic spectrum of CSF1R-associated HDLS. Three patients in the family showed typical manifestations of HDLS, while a 10-year-old gene carrier remains asymptomatic. Brain MRI revealed diffuse white matter changes in affected individuals.
NEUROLOGICAL SCIENCES
(2022)
Article
Clinical Neurology
Panagiotis Stoiloudis, Dimitrios Parissis, Nikoletta Smyrni, Thomai Stardeli, Theodora Afrantou, Eleni Konstantinopoulou, Nikolaos Grigoriadis, Panagiotis Ioannidis
Summary: HDLS is an adult onset leukodystrophy caused by mutations in the CSF1R gene. Patients may present with PPA-like symptoms, and early diagnosis is crucial for potential treatment.
NEUROLOGICAL SCIENCES
(2021)
Article
Clinical Neurology
Chujun Wu, Mengwen Wang, Xingao Wang, Wei Li, Shaowu Li, Bin Chen, Songtao Niu, Hongfei Tai, Hua Pan, Zaiqiang Zhang
Summary: This study investigated a cohort of 309 adult patients with suspected genetic leukoencephalopathies (gLEs) and characterized the genetic and phenotypic spectra of gLEs in this population. The most frequently mutated genes were identified.
Article
Clinical Neurology
Ekaterina Kazakova, Jose Alberto Tellez-Martinez, Leonardo Flores-Lagunes, Ana Luisa Sosa-Ortiz, Karol Carillo-Sanchez, Carolina Molina-Garay, Carlos Alberto Gonzalez-Dominguez, Marco Jimenez-Olivares, Francisca Fernandez-Valverde, Edwin Steven Vargas-Canas, Martha Elisa Vazquez-Memije, Ethel Awilda Garcia-Latorre, Ivan Martinez-Duncker, Carmen Alaez-Verson
Summary: This study reports the first Mexican case of AARS2 mutations causing primary ovarian failure, uterus infantilis, and early-onset dementia secondary to leukoencephalopathy. Detailed clinical, clinimetric, neuroimaging, and molecular studies were conducted. The study expands the genetic and phenotypic spectrum of AARS2-related dementia with leukoencephalopathy and ovarian failure and characterizes novel molecular variants.
FRONTIERS IN NEUROLOGY
(2023)
Article
Clinical Neurology
Ka Young Lim, Seong-Ik Kim, Hyunhee Kim, Jeongwan Kang, Jin Woo Park, Jae Kyung Won, Dong-Yeop Shin, Sung-Hye Park
Summary: This report describes two cases that confirm the clinicopathological features of chemotherapy-induced toxic leukoencephalopathy, emphasizing that chemotherapy drugs other than methotrexate can also cause this disease.
Article
Clinical Neurology
Minglei Liu, Yangyang Wang, Changhe Shi, Yanpeng Yuan, Lanjun Li, Xiaoyun Zhang, Yuming Xu, Jing Yang
Summary: This study analyzed the genetic spectrum and clinical features of Chinese adult leukoencephalopathies and compared the genetic profiles in different populations, highlighting the importance of genetic testing for accurate diagnosis and improved clinical management of these disorders.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2023)
Article
Clinical Neurology
Cong Ding, Li Zhao, Yu Zhan, Jiahao Li, Rujia Zhong, Qingwei Song, Chunbo Dong
Summary: Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a rare genetic disorder caused by mutations in the CSF1R gene, resulting in white matter changes and cognitive impairment.
NEUROLOGICAL SCIENCES
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Keith A. Josephs, Nirubol Tosakulwong, Stephen D. Weigand, Marina Buciuc, Val J. Lowe, Dennis W. Dickson, Jennifer L. Whitwell
Summary: F-18-flortaucipir PET uptake is not associated with 4R tau lesion types, but may have marginal correlation with thread-like lesions in specific brain regions and astrocytic lesions in the red nucleus.
JOURNAL OF NUCLEAR MEDICINE
(2022)
Article
Clinical Neurology
Shunsuke Koga, Akihiro Ikeda, Dennis W. Dickson
Summary: This study developed a deep learning model for differentiating tauopathies on tau-immunostained digital slide images. Using CP13-immunostained slide images for training, a random forest classifier achieved an average test score of 0.97, correctly diagnosing 29 out of 30 cases. Validation with hold-out datasets showed over 92% diagnostic accuracy without data augmentation and over 95% with augmentation.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2022)
Article
Clinical Neurology
Shunsuke Koga, Aya Murakami, Keith A. Josephs, Dennis W. Dickson
Summary: Primary progressive aphasia (PPA) is a progressive language disorder associated with neurodegenerative diseases such as frontotemporal lobar degeneration (FTLD), Alzheimer's disease (AD), and Lewy body disease (LBD). This report presents a case of a 78-year-old Caucasian woman with PPA who initially had levodopa-responsive parkinsonism and later developed cognitive impairment, visual hallucinations, and rapid eye movement sleep behavior disorder. The neuropathological assessment revealed diffuse LBD, AD, and TDP-43 stage 6, suggesting that severe cortical LBD pathology may have contributed to her progressive aphasia.
Article
Clinical Neurology
Shunsuke Koga, Xiaolai Zhou, Aya Murakami, Cristhoper Fernandez De Castro, Matthew C. Baker, Rosa Rademakers, Dennis W. Dickson
Summary: The coexistence of TDP-43 and tau pathologies is relatively common in patients with frontotemporal lobar degeneration, particularly primary age-related tauopathy and ageing-related tau astrogliopathy. Although rare, patients with FTLD can have multiple neurodegenerative proteinopathies.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2022)
Article
Clinical Neurology
Hiroaki Sekiya, Shunsuke Koga, Yoshihisa Otsuka, Norio Chihara, Takehiro Ueda, Kenji Sekiguchi, Yukihiro Yoneda, Yasufumi Kageyama, Riki Matsumoto, Dennis W. Dickson
Summary: This study compared the clinical characteristics and outcomes between later onset MSA (LO-MSA) and usual onset MSA (UO-MSA), finding that LO-MSA patients had shorter survival time. The results suggest that MSA should be considered as a differential diagnosis in elderly patients with autonomic symptoms and movement disorders.
JOURNAL OF NEUROLOGY
(2022)
Article
Multidisciplinary Sciences
Yi Xiao Jiang, Qin Cao, Michael R. Sawaya, Romany Abskharon, Peng Ge, Michael DeTure, Dennis W. Dickson, Janine Y. Fu, Rachel R. Ogorzalek Loo, Joseph A. Loo, David S. Eisenberg
Summary: This study found that amyloid fibrils in FTLD-TDP patients are formed by TMEM106B protein rather than TDP-43 protein. In addition, abundant non-fibrillar aggregated TDP-43 protein was observed.
Article
Neurosciences
Shunsuke Koga, Mariam Ishaque, W. Jeffrey Elias, Binit B. Shah, Aya Murakami, Dennis W. Dickson
Summary: This study reports the first postmortem neuropathologic findings of FUS thalamotomy in a patient with tremor-dominant PD. The results suggest that FUS thalamotomy can improve tremor symptoms and cause thalamic lesions, with implications for understanding PD-related pathology. Further pathological assessments are needed.
NPJ PARKINSONS DISEASE
(2022)
Editorial Material
Clinical Neurology
Shunsuke Koga, Hiroaki Sekiya, Nicholas B. Martin, Dennis W. Dickson
Article
Clinical Neurology
Aya Murakami, Shunsuke Koga, Hiroaki Sekiya, Bjorn Oskarsson, Kevin Boylan, Leonard Petrucelli, Keith A. Josephs, Dennis W. Dickson
Summary: This study aimed to assess and compare the burden of transactive response DNA-binding protein of 43 kDa (TDP-43) pathology and clinical features of amyotrophic lateral sclerosis (ALS) in three age groups. The study found that the amygdala and hippocampus are vulnerable to TDP-43 pathology in older patients with ALS.
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
Clinical Neurology
Shunsuke Koga, Aya Murakami, Nicholas B. Martin, Dennis W. Dickson
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2023)
Article
Clinical Neurology
Hiroaki Sekiya, Shunsuke Koga, Aya Murakami, Miki Kawazoe, Minji Kim, Nicholas B. Martin, Ryan J. Uitti, William P. Cheshire, Zbigniew K. Wszolek, Dennis W. Dickson
Summary: The study compared the diagnostic accuracy of the MDS criteria and second consensus criteria for MSA, finding that the MDS criteria had higher specificity for clinically established and probable MSA, while the second consensus criteria had higher sensitivity for probable and possible MSA.
Article
Multidisciplinary Sciences
Junhao Li, Manoj K. Jaiswal, Jo-Fan Chien, Alexey Kozlenkov, Jinyoung Jung, Ping Zhou, Mahammad Gardashli, Luc J. Pregent, Erica Engelberg-Cook, Dennis W. Dickson, Veronique V. Belzil, Eran A. Mukamel, Stella Dracheva
Summary: The repeat expansion in the C9orf72 gene is a common genetic cause of ALS and FTD. The study found pervasive alterations in gene expression and chromatin accessibility in neurons and astrocytes of C9-ALS patients, as well as gene expression changes in glial cells of C9-FTD patients. These findings indicate unique molecular disruptions in different cell types, brain regions, and diseases.
NATURE COMMUNICATIONS
(2023)
Article
Genetics & Heredity
Aimee R. Herdt, Hui Peng, Dennis W. Dickson, Todd E. Golde, Elizabeth A. Eckman, Chris W. Lee
Summary: Krabbe disease is a neurologic disorder characterized by the accumulation of psychosine in the CNS. In a mouse model, treatment with AAV1-GALC, a viral vector expressing GALC, significantly improved body weight gain and survival, as well as normalized psychosine levels in the brain.
Letter
Clinical Neurology
Miki Kawazoe, Shunsuke Koga, Dennis W. Dickson
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2023)
