Article
Clinical Neurology
Aaron Jesuthasan, Danielle Sequeira, Harpreet Hyare, Hans Odd, Peter Rudge, Tze How Mok, Akin Nihat, John Collinge, Simon Mead
Summary: This study reviewed the reporting sensitivity of MRI scans for sporadic Creutzfeldt-Jakob disease (sCJD) cases a decade later. While there has been improvement in local MRI reporting, characteristic abnormalities are still significantly under-detected on initial scans. Sensitivity is higher when the cerebral cortex and multiple regions are involved.
JOURNAL OF NEUROLOGY
(2022)
Article
Medicine, Research & Experimental
Jennifer Myskiw, Lise Lamoureux, Anne Peterson, David Knox, Gerard H. Jansen, Michael B. Coulthart, Stephanie A. Booth
Summary: Creutzfeldt-Jakob disease (CJD) is a group of transmissible neurodegenerative diseases with diverse phenotypes. We optimized and developed a capillary-based western assay to detect and characterize prion proteins from patients with CJD, which displayed outstanding sensitivity and specificity. This novel assay has the potential to enhance current detection methods and preserve valuable samples.
LABORATORY INVESTIGATION
(2023)
Article
Virology
Nicholas Brennecke, Ignazio Cali, Tze How Mok, Helen Speedy, Laszlo L. P. Hosszu, Christiane Stehmann, Laura Cracco, Gianfranco Puoti, Thomas W. Prior, Mark L. Cohen, Steven J. Collins, Simon Mead, Brian S. Appleby
Summary: Genetic prion disease accounts for 10-15% of prion diseases, with smaller repeat insertions having unclear pathogenicity. This study focused on the 2-octapeptide repeat genetic variant, finding it to be a low-risk variant with very low penetrance. Therefore, predictive genetic testing for asymptomatic blood relatives may not be justified.
Review
Clinical Neurology
Johnny Tam, John Centola, Hatice Kurudzhu, Neil Watson, Janet MacKenzie, Margaret Leitch, Terri Hughes, Alison Green, David Summers, Marcelo Barria, Colin Smith, Suvankar Pal
Summary: This study characterized the clinical features of young individuals with sporadic Creutzfeldt-Jakob disease (sCJD) using data from UK national CJD surveillance. The findings showed that young-onset sCJD is more likely to present with neuropsychiatric symptoms and headache, longer disease duration, and lower sensitivity of RT-QuIC. These results provide guidance for evaluating younger individuals with rapidly progressive cognitive and neuropsychiatric decline and emphasize the importance of additional vigilance for atypical features.
JOURNAL OF NEUROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Hideyuki Hara, Junji Chida, Agriani Dini Pasiana, Keiji Uchiyama, Yutaka Kikuchi, Tomoko Naito, Yuichi Takahashi, Junji Yamamura, Hisashi Kuromatsu, Suehiro Sakaguchi
Summary: Prions, infectious agents causing prion diseases like Creutzfeldt-Jakob disease, can be transmitted through medical instruments used for preclinical CJD patients. Investigating sterilization methods, ozone gas and vaporized hydrogen peroxide were found to reduce prion infectivity on stainless steel wires. Combining ozone gas with vaporized hydrogen peroxide showed more potent sterilization effects against prions on the wires compared to using either agent alone.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Clinical Neurology
Andrea Mastrangelo, Angela Mammana, Simone Baiardi, Dorina Tiple, Elisa Colaizzo, Marcello Rossi, Luana Vaianella, Barbara Polischi, Michele Equestre, Anna Poleggi, Sabina Capellari, Anna Ladogana, Piero Parchi
Summary: The introduction of the Real-Time Quaking-Induced Conversion assay has led to a revision of the diagnostic criteria for sporadic Creutzfeldt-Jakob disease. This study compares the diagnostic value of the old and amended criteria and explores different combinations of clinical variables and biomarker results. The results show that CSF RT-QuIC is highly sensitive and specific for diagnosing CJD, and the Q-CM criteria provide a high diagnostic value.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Article
Biochemistry & Molecular Biology
Dong Hwan Kim, Jaehyeon Kim, Hakmin Lee, Dongyun Lee, So Myoung Im, Ye Eun Kim, Miryeong Yoo, Yong-Pil Cheon, Jason C. Bartz, Young-Jin Son, Eun-Kyoung Choi, Yong-Sun Kim, Jae-Ho Jeon, Hyo Shin Kim, Sungeun Lee, Chongsuk Ryou, Tae-gyu Nam
Summary: Acylthiosemicarbazides are able to inhibit protein aggregation and could be potential therapeutics for prion diseases.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Clinical Neurology
Zhongyun Chen, Min Chu, Li Liu, Jing Zhang, Yu Kong, Kexin Xie, Yue Cui, Hong Ye, Junjie Li, Lin Wang, Liyong Wu
Summary: Genetic prion diseases (gPrDs) presenting with frontotemporal dementia (FTD) are characterized by early onset, high incidence of positive family history, overlapping clinical features with prion diseases and FTD, and ancillary features closer to FTD. PRNP mutations may be a rare cause in the FTD spectrum, and PRNP genotyping should be considered in patients with these features.
ALZHEIMERS RESEARCH & THERAPY
(2022)
Review
Pharmacology & Pharmacy
Simone Baiardi, Angela Mammana, Sabina Capellari, Piero Parchi
Summary: Human prion diseases are rare, heterogeneous, and rapidly progressive neurodegenerative disorders characterized by misfolded prion protein aggregation and self-propagation. They occur in idiopathic, genetically determined, and acquired forms with different etiologies and phenotypic variants. This review provides an up-to-date overview of potential therapeutic targets in prion diseases, discussing the results obtained in cell and animal models and human trials, as well as the challenges associated with developing effective therapies and informative clinical trials. The most promising therapeutic strategies currently focus on targeting cellular PrP to prevent misfolded PrP formation or promote its elimination, such as passive immunization and gene therapy with antisense oligonucleotides.
EXPERT OPINION ON THERAPEUTIC TARGETS
(2023)
Article
Clinical Neurology
Vincenzo Mastrangelo, Elena Merli, Janet C. Rucker, Eric R. Eggenberger, David S. Zee, Pietro Cortelli
Summary: Fatal familial insomnia (FFI) is a rare inherited prion disease characterized by sleep, autonomic, and motor disturbances. Excessive saccadic intrusions were found to be a prominent early diagnostic clue for FFI in patients with severe insomnia. The involvement of the thalamus in FFI also suggests its role in the control of steady fixation.
ANNALS OF NEUROLOGY
(2021)
Article
Clinical Neurology
Renzo Manara, Federica Fragiacomo, Anna Ladogana, Luana Vaianella, Giulia Camporese, Giovanni Zorzi, Sabrina Vicinanza, Gianluigi Zanusso, Maurizio Pocchiari, Annachiara Cagnin
Summary: This study aimed to investigate brain MRI abnormalities in patients with rapidly progressive dementia (RPD) with and without a diagnosis of Creutzfeldt-Jakob disease (CJD). The study found that DWI-MRI results had an impact on the reliability of CJD diagnosis, while specific DWI patterns helped differentiate CJD from alternative diagnoses.
JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Peter Hermann, Matthias Schmitz, Maria Cramm, Stefan Goebel, Timothy Bunck, Julia Schuette-Schmidt, Walter Schulz-Schaeffer, Christine Stadelmann, Jakob Matschke, Markus Glatzel, Inga Zerr
Summary: This study evaluated the application of CSF real-time quaking-induced conversion in Creutzfeldt-Jakob disease surveillance, investigating its test accuracy, influencing factors, and associations with disease incidence. The results showed that the overall sensitivity of the test for sporadic Creutzfeldt-Jakob disease was 90% and the specificity was 99%. Lower sensitivity was associated with early disease stage and longer survival, while false positives were more common in patients with inflammatory CNS diseases. The surveillance improved after the amendment of diagnostic criteria, with no significant changes in incidence during the COVID-19 pandemic.
JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Christina Kerner, Keisi Kotobelli, Brian S. Appleby, Mark L. Cohen, Hesham Abboud
Summary: Analysis of autopsy specimens from patients suspected of Creutzfeldt-Jakob disease revealed that autoimmune encephalitis exhibits diffuse inflammation and potential for neurological recovery. These findings are preliminary and require further confirmation.
JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Samuel M. Jones, Evelyn B. Lazar, Amanda L. Porter, Christian C. Prusinski, Matthew R. Brier, Robert C. Bucelli, Gregory S. Day
Summary: This study investigates the clinical, laboratory, and pathological features associated with false negative results in RT-QuIC testing for prion disease. It found that patients with negative RT-QuIC results were younger, had lower markers of neuronal damage, and had a longer symptomatic duration of disease. Therefore, other test results should be considered when evaluating patients with suspected prion disease.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Review
Clinical Neurology
Brian S. Appleby, Shashirekha Shetty, Mohamed Elkasaby
Summary: This article reviews the genetic aspects of human prion disease, including the impact of genetic variations on the disease and the related epidemiology, clinicopathologic phenotype, diagnostics, clinical management, and potential treatment approaches.
FRONTIERS IN NEUROLOGY
(2022)
Article
Clinical Neurology
Hiroyuki Honda, Kosuke Matsuzono, Kota Satoh, Masayoshi Fujisawa, Satoshi O. Suzuki, Chiaki Furuyama, Tetsuyuki Kitamoto, Shigeru Fujimoto, Koji Abe, Toru Iwaki
Summary: Immunohistochemical detection of PrP in cutaneous samples revealed abnormal PrP deposits in patients with GPI-anchorless PrP disease, particularly localized at the basement membrane and colocalized with laminin. This method could be used for definitive diagnosis of the disease.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Article
Clinical Neurology
Motoi Yoshimura, Hiroyuki Honda, Naokazu Sasagasako, Shinichiro Mori, Hideomi Hamasaki, Satoshi O. Suzuki, Takashi Ishii, Toshiharu Ninomiya, Jun-Ichi Kira, Toru Iwaki
Summary: The study revealed decreased expression of PCBP2 in neurons of some ALS and FTLD patients, while its occurrence in TDP-43-positive inclusions was a rare phenomenon.
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2021)
Article
Clinical Neurology
Shinichiro Mori, Satoshi O. Suzuki, Hiroyuki Honda, Hideomi Hamasaki, Nobutaka Sakae, Naokazu Sasagasako, Hirokazu Furuya, Toru Iwaki
Summary: Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disease characterized by progressive ossification of skeletal muscles. The causative gene for FOP has been identified as the ACVR1 gene, with mutations like R206H being common. Additionally, rare mutations like G356D have been found in some FOP patients.
Article
Clinical Neurology
Hiroyuki Honda, Shinichiro Mori, Akihiro Watanabe, Naokazu Sasagasako, Shoko Sadashima, Trang Dong, Katsuya Satoh, Noriyuki Nishida, Toru Iwaki
Summary: The autopsy of a 72-year-old female sCJD patient revealed widespread PrP deposits in the brain and systemic organs, indicating an association between long-term disease duration and PrP deposition in organs. This case highlights the importance of general autopsies in sCJD cases for establishing infection control procedures and examining specific organs.
Article
Clinical Neurology
Hideomi Hamasaki, Masahiro Shijo, Ayaka Nakamura, Hiroyuki Honda, Yuichi Yamada, Masanao Oda, Tomoyuki Ohara, Toshiharu Ninomiya, Toru Iwaki
Summary: This study investigated the relationship between degenerative changes of the brain and heart, with reference to AD pathologies, ATTR deposition, and cardiac fibrosis in a Japanese population. It found that cardiac ATTR deposition correlated with AD brain pathology among older adults aged 90 or below.
Letter
Clinical Neurology
Kosuke Matsuzono, Younhee Kim, Hiroyuki Honda, Yuhei Anan, Yuto Hashimoto, Ichiya Sano, Toru Iwaki, Tetsuyuki Kitamoto, Shigeru Fujimoto
JOURNAL OF THE NEUROLOGICAL SCIENCES
(2021)
Article
Clinical Neurology
Shinichiro Mori, Hiroyuki Honda, Hideomi Hamasaki, Naokazu Sasagasako, Satoshi O. Suzuki, Hirokazu Furuya, Takayuki Taniwaki, Toru Iwaki
Summary: SPG11 is a common hereditary spastic paraplegia characterized by spastic paraplegia, cognitive impairment, dementia, and parkinsonism. Neuropathological analysis reveals neurodegeneration and unique SQSTM1-positive neuronal inclusions, suggesting a causal connection between TDP-43 proteinopathy and autophagy dysfunction in SPG11.
Article
Clinical Neurology
Kaoru Yagita, Hiroyuki Honda, Tomoyuki Ohara, Hideomi Hamasaki, Sachiko Koyama, Hideko Noguchi, Akane Mihara, Taro Nakazawa, Jun Hata, Toshiharu Ninomiya, Toru Iwaki
Summary: This study evaluated the aging-related tau astrogliopathy (ARTAG) in 110 autopsies and found differences in the distribution and affected variables of ARTAG across Alzheimer disease (AD) and cognitive healthy cases (HC). The findings suggest that age at death, neurofibrillary tangle Braak stage, gender, and Thal phase significantly affect the presence of ARTAG in both AD and HC individuals.
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2022)
Article
Clinical Neurology
Kaoru Yagita, Hideko Noguchi, Sachiko Koyama, Hideomi Hamasaki, Takashi Komori, Shinichi Aishima, Takayuki Kosaka, Mitsuharu Ueda, Yoshihiro Komohara, Akihiro Watanabe, Naokazu Sasagasako, Toshiharu Ninomiya, Yoshinao Oda, Hiroyuki Honda
Summary: The study aimed to understand the differential effects of sporadic Creutzfeldt-Jakob disease (sCJD) on the hippocampus and other neocortical areas. By examining the histological patterns of cellular prion protein (PrP (c)) and abnormal prion protein (PrPSc) in the hippocampi of sCJD patients and normal controls (NCs), the chronology of histopathological alterations in the CA4 region in sCJD patients was highlighted.
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2022)
Article
Clinical Neurology
Kaoru Yagita, Naokazu Sasagasako, Sachiko Koyama, Hideko Noguchi, Hiroyuki Honda
Summary: This unique autopsy case reveals that ALS with TDP-43 pathology could coexist with globular glial tau inclusions, suggesting the existence of common pathological mechanisms between ALS and globular glial inclusions.
Article
Multidisciplinary Sciences
Sachiko Koyama, Hideko Noguchi, Kaoru Yagita, Hideomi Hamasaki, Masahiro Shijo, Motoi Yoshimura, Kohei Inoshita, Naokazu Sasagasako, Hiroyuki Honda
Summary: This study investigates the presence of prion proteins in endocrine and exocrine tissues and their molecular properties in comparison to normal brain tissue. The findings are important for understanding and controlling prion disease.
SCIENTIFIC REPORTS
(2022)
Article
Clinical Neurology
Hiroyuki Honda, Motoi Yoshimura, Hajime Arahata, Kaoru Yagita, Shoko Sadashima, Hideomi Hamasaki, Masahiro Shijo, Sachiko Koyama, Hideko Noguchi, Naokazu Sasagasako
Summary: FUS mutations play a significant role in ALS-FUS and colocalize with other hnRNPs such as TDP43, PCBP2, and PCBP1, suggesting impaired RNA metabolism.
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2023)
Article
Clinical Neurology
Kaoru Yagita, Shoko Sadashima, Sachiko Koyama, Hideko Noguchi, Hideomi Hamasaki, Naokazu Sasagasako, Hiroyuki Honda
Summary: Neuronal intranuclear inclusions (NIIs) and Marinesco bodies (MBs) both contain ribosomal protein SA (RPSA) and are related to polyglutamine diseases and aging. RPSA is co-localized with polyQ aggregations in NIIs, and its distribution is mosaic-like. The unique organization of RPSA and p62 suggests a common mechanism in the formation of NIIs and MBs. The nuclear fraction of RPSA is increased in HD patients compared to normal elderly individuals.
Article
Clinical Neurology
Hiroyuki Honda, Kaoru Yagita, Hajime Arahata, Hideomi Hamasaki, Hideko Noguchi, Sachiko Koyama, Naokazu Sasagasako
Summary: FUS mutations are important in familial amyotrophic lateral sclerosis (ALS). FUS-positive neuronal cytoplasmic inclusions (FUS-NCI) are the pathological hallmark, known as FUS proteinopathy. This study examined the expression of MxA in neurons with FUS-NCI and found that increased cytoplasmic MxA expression is associated with the formation of FUS-NCI in ALS-FUS patients.
Letter
Gastroenterology & Hepatology
Kosuke Matsuzono, Younhee Kim, Hiroyuki Honda, Yuhei Anan, Masato Tsunoda, Yusuke Amano, Noriyoshi Fukusima, Toru Iwaki, Tetsuyuki Kitamoto, Shigeru Fujimoto
AMERICAN JOURNAL OF GASTROENTEROLOGY
(2021)