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)
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)
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)
Article
Neurosciences
Fabrizio Biundo, Violeta Chitu, Gabriel G. L. Shlager, Eun S. Park, Maria E. Gulinello, Kusumika Saha, Harmony C. Ketchum, Christopher Fernandes, Solen Gokhan, Mark F. Mehler, E. Richard Stanley
Summary: Studies have shown that loss of microglia cells can lead to behavioral deficits, pathology, and increased Csf2 expression in CSF1R-deficient mice, but not neural deletion. Additionally, increased Csf2 expression was observed in callosal astrocytes, oligodendrocytes, and microglia, with increased cell densities in regions with activated microglia in CSF1R-deficient mice. These findings confirm the involvement of microglia in the pathogenesis of ALSP and provide insights for future therapeutic strategies.
Article
Multidisciplinary Sciences
Miguel A. Arreola, Neelakshi Soni, Joshua D. Crapser, Lindsay A. Hohsfield, Monica R. P. Elmore, Dina P. Matheos, Marcelo A. Wood, Vivek Swarup, Ali Mortazavi, Kim N. Green
Summary: The study showed that microglial CSF1R haploinsufficiency leads to microglial dysregulation, characterized by reduced expression of cellular markers, and synaptic and extracellular matrix deficits. Treatment with a CSF1R inhibitor prevented these abnormalities, highlighting the potential therapeutic benefit of targeting CSF1R in mitigating the pathogenesis of the disease.
Article
Medicine, General & Internal
Hee Jung Kwon, Duk L. Na, Hee Jin Kim, Yeon-Lim Suh
Summary: Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia is a rare neurological disorder characterized by dysarthria and cognitive decline. It is associated with T2 hyperintensities in subcortical and periventricular white matter. Genetic analysis identified heterozygous variants in the colony stimulating factor-1 receptor gene in the diagnosed cases. Pathological examination revealed severe white matter degeneration with loss of myelinated axons, but varying levels of axonal spheroids and pigmented macrophages. This disorder should be considered in patients with presenile dementia and diffuse white matter lesions.
Article
Clinical Neurology
Pei-Chien Tsai, Jong-Ling Fuh, Chih-Chao Yang, Anna Chang, Li-Ming Lien, Pei-Ning Wang, Kuan-Lin Lai, Yu-Shuen Tsai, Yi-Chung Lee, Yi-Chu Liao
Summary: CSF1R mutations account for 3.5% of adult-onset leukoencephalopathy in Taiwan, leading to cognitive decline, psychiatric symptoms, and rapid deterioration of cognitive function in affected patients.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Pokhraj Prakashchandra Suthar, Miral Jhaveri, Mustafa Mafraji
Summary: A 44-year-old previously healthy man presented with progressive cognitive decline, depression, urinary incontinence, and inability to perform daily tasks. His brother had a similar decline before passing away. Extensive evaluations did not reveal a specific cause.
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
Cristina Moreno Loscertales, Paula Canasto Jimenez, Mario Bautista Lacambra, Luisa Tique Rojas, Silvia Izquierdo Alvarez, Eugenia Marta Moreno
Summary: This paper reports a case of a 67-year-old man with a history of progressive impairment of behavioral and cognitive functions. The patient presented symptoms such as apathy, inhibition, tendency to mutism, and deficits in complex planning skills. The diagnosis was confirmed as colony-stimulating factor 1 receptor-related adult-onset leukoencephalopathy based on genetic testing and brain imaging findings. This is the first documented case in Spain, highlighting the underdiagnosis of this condition and the importance of brain imaging for its diagnosis.
ALZHEIMER DISEASE & ASSOCIATED DISORDERS
(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
Immunology
Xin Li, Banglian Hu, Xiaoyan Guan, Ziwei Wang, Yuhang Zhou, Hao Sun, Xian Zhang, Yanfang Li, Xiaohua Huang, Yingjun Zhao, Xin Wang, Huaxi Xu, Yun-Wu Zhang, Zhanxiang Wang, Honghua Zheng
Summary: In this study, researchers used CRISPR/Cas9 genome editing technology to generate a mouse model with CSF1R gene haploinsufficiency, to investigate the pathogenic mechanism of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and the therapeutic effects of minocycline. The study found that CSF1R deficiency leads to aberrant microglial activation, and minocycline can suppress this activation and improve behavioral and pathological defects.
JOURNAL OF NEUROINFLAMMATION
(2023)
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
Neurosciences
Ashok Vardhan Reddy Tallapalli, Saraswati Nashi, Sneha D. Kamath, P. R. Srijithesh, Girish B. Kulkarni, Suvarna Alladi
Summary: A case of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) presenting with rapid cognitive decline, Parkinsonism, apraxia, and stimulus sensitive myoclonus is reported for the first time in India.
Article
Clinical Neurology
Eun Hee Sohn, Juyoun Lee, Ae Young Lee, Jin-Hong Shin
Summary: CSF1R-related leukoencephalopathy is a common cause of adult-onset leukodystrophy, caused by mutation of the CSF1R gene. Brain MRI findings in asymptomatic patients may not be well recognized, as shown in this representative case tracking the progression of the disease.
Article
Neurosciences
Katsuya Nakamura, Kunihiro Yoshida, Akira Matsushima, Yusaku Shimizu, Shunichi Sato, Hiroyuki Yahikozawa, Shinji Ohara, Masanobu Yazawa, Masao Ushiyama, Mitsuto Sato, Hiroshi Morita, Atsushi Inoue, Shu-ichi Ikeda
Article
Clinical Neurology
Kunihiro Yoshida, Satoshi Kuwabara, Katsuya Nakamura, Ryuta Abe, Akira Matsushima, Minako Beppu, Yoshitaka Yamanaka, Yuji Takahashi, Hidenao Sasaki, Hidehiro Mizusawa
JOURNAL OF THE NEUROLOGICAL SCIENCES
(2018)
Letter
Clinical Neurology
Yuka Ogawa, Katsuya Nakamura, Naoki Ezawa, Tomomi Yamaguchi, Tsuneaki Yoshinaga, Daigo Miyazak, Tomoki Kosho, Yoshiki Sekijima
JOURNAL OF THE NEUROLOGICAL SCIENCES
(2019)
Article
Neurosciences
Lien Nguyen, Fabio Montrasio, Amrutha Pattamatta, Solaleh Khoramian Tusi, Olgert Bardhi, Kevin D. Meyer, Lindsey Hayes, Katsuya Nakamura, Monica Banez-Coronel, Alyssa Coyne, Shu Guo, Lauren A. Laboissonniere, Yuanzheng Gu, Saravanakumar Narayanan, Benjamin Smith, Roger M. Nitsch, Mark W. Kankel, Mia Rushe, Jeffrey Rothstein, Tao Zu, Jan Grimm, Laura P. W. Ranum
Letter
Clinical Neurology
Teruya Morizumi, Akihiro Ueno, Ken Takasone, Kazuki Ozawa, Tsuneaki Yoshinaga, Katsuya Nakamura, Yoshiki Sekijima
JOURNAL OF THE NEUROLOGICAL SCIENCES
(2020)
Article
Medicine, General & Internal
Ken Takasone, Teruya Morizumi, Katsuya Nakamura, Yusuke Mochizuki, Tsuneaki Yoshinaga, Shingo Koyama, Yoshiki Sekijima
Article
Medicine, General & Internal
Yuya Aono, Yasuhiro Hamatani, Nagaaki Katoh, Mayuko Nakagawa, Katsuya Nakamura, Masahide Yazaki, Fuyuki Kametani, Moritake Iguchi, Ikuko Murakami, Hisashi Ogawa, Mitsuru Abe, Masaharu Akao, Yoshiki Sekijima
Summary: The patient, an 82-year-old Japanese man with no family history of amyloidosis, was diagnosed with severe ATTR amyloid deposits. A genetic analysis revealed a missense variant in the TTR gene, which was predicted to only modestly alter the structure and function of the TTR protein. This variant may be associated with an elderly-onset cardiac-dominant ATTRv phenotype.
Article
Genetics & Heredity
Hiroaki Hanafusa, Yoshihiko Hidaka, Tomomi Yamaguchi, Hisashi Shimojo, Takanori Tsukahara, Tsubasa Murase, Daisuke Matsuoka, Nao Chiba, Shun Shimada, Hirokazu Morokawa, Norio Omori, Hironori Minoura, China Nagano, Kyoko Takano, Katsuya Nakamura, Keiko Wakui, Yoshimitsu Fukushima, Takeshi Uehara, Yozo Nakazawa, Kazumoto Iijima, Kandai Nozu, Tomoki Kosho
Summary: TRPC6, a gene encoding the transient receptor potential channel, is involved in the formation of the slit diaphragm in podocytes, and its abnormalities can lead to various glomerular diseases. We reported a patient with rapidly progressing infantile nephrotic syndrome, carrying a heterozygous missense TRPC6 variant, representing the first case associated with diffuse mesangial sclerosis (DMS) in TRPC6-related renal disorders.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2021)
Article
Medicine, General & Internal
Yusuke Takahashi, Yusuke Mochizuki, Katsuya Nakamura, Nagaaki Katoh, Yoshiki Sekijima
Summary: A 41-year-old woman with POEMS syndrome developed cerebral infarctions and had stenotic lesions resembling moyamoya disease. Quasi-moyamoya disease may be an important phenotype of systemic vasculopathies in POEMS syndrome.
Editorial Material
Medicine, General & Internal
Masateru Tajiri, Minori Kodaira, Katsuya Nakamura, Yoshiki Sekijima
Editorial Material
Genetics & Heredity
Yasufumi Kondo, Tsuneaki Yoshinaga, Katsuya Nakamura, Tomomi Yamaguchi, Masumi Ishikawa, Tomoki Kosho, Yoshiki Sekijima
Summary: The clinical effect of a heterozygous missense variant of HTRA1 on cerebral small vessel disease (CSVD) was investigated in a large Japanese family. The study revealed that patients with the p.A252T variant had neurologic symptoms and brain MRI abnormalities. Some carriers of the variant only showed CSVD on the MRI, while others were unaffected. The study also found that the severity of neurologic symptoms in variant carriers was influenced by gender and atherosclerotic risk factors.
NEUROLOGY-GENETICS
(2023)
Article
Medicine, General & Internal
Katsuya Nakamura, Tsuneaki Yoshinaga, Minori Kodaira, Emiko Kise, Tomoki Kosho, Yoshiki Sekijima
Summary: This study reported a 37-year-old Japanese male patient with KIF1A-associated neurological disorder (KAND), who exhibited motor developmental delay, intellectual disability, and slowly progressive cerebellar ataxia, hypotonia, and optic neuropathy. A molecular diagnosis revealed a novel variant of KIF1A. Neuroradiology studies showed atrophy of the cerebellum and cerebral hemisphere, which progressed slowly.
Article
Genetics & Heredity
Katsuya Nakamura, Saki Mukai, Yuka Takezawa, Yuika Natori, Akari Miyazaki, Yuichiro Ide, Mayu Takebuchi, Kana Nanato, Mizuki Katoh, Harue Suzuki, Akiko Sakyu, Tomomi Kojima, Emiko Kise, Hiroaki Hanafusa, Tomoki Kosho, Koichiro Kuwahara, Yoshiki Sekijima
Summary: In this study, the diagnostic ability of urinary mulberry bodies and cells (MBs/MCs) for Fabry disease (FD) was retrospectively evaluated. The results showed that urinary MBs/MCs testing exhibits high accuracy in diagnosing FD and should be considered as an initial evaluation method, especially for female patients, prior to genetic testing.
MOLECULAR GENETICS AND METABOLISM REPORTS
(2023)
Article
Neurosciences
Akira Takekoshi, Akio Kimura, Nobuaki Yoshikura, Isamu Yamakawa, Makoto Urushitani, Katsuya Nakamura, Kunihiro Yoshida, Takayoshi Shimohata
Summary: Neuropil antibodies were detected in 17.9% of patients with idiopathic sporadic ataxia (ISA), and these patients showed more frequent pure cerebellar ataxia. Some neuropil antibody-positive ISA patients responded well to immunotherapy.