Article
Clinical Neurology
Jessica Roos, Stefanie Muller, Anne Giese, Silke Appenzeller, Erich Bernd Ringelstein, Jens Fiehler, Klaus Berger, Arndt Rolfs, Christian Hagel, Gregor Kuhlenbaumer
Summary: This study describes the clinical and cranial MRI features of the Pontine Autosomal Dominant Microangiopathy with Leukoencephalopathy (PADMAL) family and correlates them with the segregation analysis of the causative collagen 4A1 gene (COL4A1) variant. The study concludes that early diagnosis of PADMAL can be made based on cranial MRI, clinical signs, and confirmatory sequencing of the COL4A1 miRNA-29-binding site. The study also finds that variants in the COL4A1 miRNA-29-binding site do not contribute significantly to sporadic stroke.
JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Qing Li, Chengfeng Wang, Wei Li, Zaiqiang Zhang, Shanshan Wang, Autongsha Wupuer, Xiao Hu, Kalibinuer Wumaier, Yi Zhu, Hongyan Li, Wengui Yu
Summary: PADMAL is a rare hereditary cerebral small vessel disease, and a novel COL4A1 gene mutation was identified in a Chinese family. This mutation may result in overexpression of COL4A1, leading to clinical and MRI evidence of PADMAL.
TRANSLATIONAL STROKE RESEARCH
(2022)
Article
Multidisciplinary Sciences
Minwoo Wendy Jang, Doo-Yi Oh, Eunyoung Yi, Xuezhong Liu, Jie Ling, Nayoung Kim, Kushal Sharma, Tai Young Kim, Seungmin Lee, Ah-Reum Kim, Min Young Kim, Min-A Kim, Mingyu Lee, Jin-Hee Han, Jae Joon Han, Hye-Rim Park, Bong Jik Kim, Sang-Yeon Lee, Dong Ho Woo, Jayoung Oh, Soo-Jin Oh, Tingting Du, Ja-Won Koo, Seung-Ha Oh, Hyun-Woo Shin, Moon-Woo Seong, Kyu-Yup Lee, Un-Kyung Kim, Jung Bum Shin, Shushan Sang, Xinzhang Cai, Lingyun Mei, Chufeng He, Susan H. Blanton, Zheng-Yi Chen, Hongsheng Chen, Xianlin Liu, Aida Nourbakhsh, Zaohua Huang, Kwon-Woo Kang, Woong-Yang Park, Yong Feng, C. Justin Lee, Byung Yoon Choi
Summary: The study identified a deafness gene TMEM43 associated with progressive deafness, mainly expressed in cochlear glia-like supporting cells. Cochlear implantation was performed on patients with ANSD caused by TMEM43 gene mutation, successfully restoring speech discrimination.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Clinical Neurology
Mao Mukai, Ai Hamano, Ikuko Mizuta, Isao Yokota, Akiko Watanabe-Hosomi, Hiraku Matsuura, Takashi Koizumi, Jun Matsuura, Tomoyuki Ohara, Shigenori Matsushima, Satoshi Teramukai, Kei Yamada, Toshiki Mizuno
Summary: This study aimed to clarify the association between cerebrovascular reactivity and stroke in CADASIL patients. Among the 14 CADASIL patients studied, those with stroke had significantly lower cerebral blood flow in the thalamus. Thus, there is an association between cerebrovascular reactivity and stroke in CADASIL patients.
FRONTIERS IN NEUROLOGY
(2023)
Article
Neurosciences
Robert X. Smith, Jeremy F. Strain, Aaron Tanenbaum, Anne M. Fagan, Jason Hassenstab, Eric McDade, Suzanne E. Schindler, Brian A. Gordon, Chengjie Xiong, Jasmeer Chhatwal, Clifford Jack, Celeste Karch, Sarah Berman, Jared R. Brosch, James J. Lah, Adam M. Brickman, David M. Cash, Nick C. Fox, Neill R. Graff-Radford, Johannes Levin, James Noble, David M. Holtzman, Colin L. Masters, Martin R. Farlow, Christoph Laske, Peter R. Schofield, Daniel S. Marcus, John C. Morris, Tammie L. S. Benzinger, Randall J. Bateman, Beau M. Ances
Summary: The study aimed to identify a global resting-state functional connectivity signature in mutation carriers from the Dominantly Inherited Alzheimer Network (DIAN), and found that the gFC was reduced in MC compared with NC participants. The gFC was associated with biomarkers used for assessing the AT(N) framework, showing a biphasic change suggesting early changes associated with CSF amyloid and later changes associated with hippocampal volume.
BRAIN CONNECTIVITY
(2021)
Article
Genetics & Heredity
Chaofan Zhang, Juliana F. Mazzeu, Jesper Eisfeldt, Christopher M. Grochowski, Janson White, Zeynep C. Akdemir, Shalini N. Jhangiani, Donna M. Muzny, Richard A. Gibbs, Anna Lindstrand, James R. Lupski, V. Reid Sutton, Claudia M. B. Carvalho
Summary: Robinow syndrome is a genetically heterogeneous disorder characterized by skeletal dysplasia and distinctive facial features. Studies have identified rare variants in multiple genes related to the WNT/planar cell polarity signaling pathway as underlying the etiology of RS. This research identified pathogenic variants in DVL1, ROR2, and NXN genes in a cohort of individuals with RS, further supporting the role of WNT signaling in skeletal development and maintenance.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2021)
Article
Clinical Neurology
Mai Kikumoto, Takashi Kurashige, Tomohiko Ohshita, Kodai Kume, Osamu Kikumoto, Tomohisa Nezu, Shiro Aoki, Kazuhide Ochi, Hiroyuki Morino, Eiichi Nomura, Hiroshi Yamashita, Mayumi Kaneko, Hirofumi Maruyama, Hideshi Kawakami
Summary: Pontine autosomal dominant microangiopathy and leukoencephalopathy is a hereditary cerebral small vessel disease caused by pathogenic variants in COL4A1 3' UTR. The appearance of multiple oval small infarctions in the pons resembling raisin bread, known as the 'raisin bread sign', is a characteristic radiological feature of this disease. The discovery of this sign has important implications for accurate diagnosis and evaluation of patients with undetermined juvenile cerebral vascular disorder.
BRAIN COMMUNICATIONS
(2023)
Article
Clinical Neurology
Chen Zhang, Shaowu Li, Wei Li, Songtao Niu, Xingao Wang, Zaiqiang Zhang
Summary: This study analyzed the clinical and genetic characteristics of CADASIL patients in China based on exon classification, revealing differences in features between patients with mutations in exons 3-4, exon 11, and other exons. Patients with exon 11 mutations showed unique characteristics such as being diagnosed at an older age, having the lowest mRS scores, and being more likely to have specific neuroimaging findings. No significant differences were found between patients with mutations in exons 3-4 and those with mutations in other exons.
EUROPEAN NEUROLOGY
(2021)
Article
Genetics & Heredity
Saskia Koenig, Manfred Fliegauf, Manuel Rhiel, Bodo Grimbacher, Tatjana Cornu, Toni Cathomen, Claudio Mussolino
Summary: This study developed allele-specific CRISPR-Cas9 nucleases to selectively disrupt mutant alleles of the STAT3 gene, but the results showed that repairing gene mutations in AD-HIES by allele-specific disruption was not able to restore STAT3-dependent signaling effectively.
Article
Medicine, General & Internal
Jing W. Goh, Satyaki Kundu, Ragunath Durairajan
Summary: This research describes a case of CADASIL in a man in his 40s who experienced temporary left-sided weakness and facial numbness. His family history and brain MRI findings were indicative of CADASIL, and genetic testing later confirmed the presence of a NOTCH3 gene mutation.
CUREUS JOURNAL OF MEDICAL SCIENCE
(2023)
Article
Medicine, General & Internal
Shoaib Ashraf, Nishant Allena, Elina Shrestha, Manjeet Dhallu, Misbahuddin Khaja
Summary: CADASIL is an inherited and common cerebral vascular disease with various symptoms. Diagnosis can be made through personal and family history, skin biopsy, and MRI. Current treatment focuses on reducing risk factors and managing symptoms.
CUREUS JOURNAL OF MEDICAL SCIENCE
(2022)
Article
Medicine, General & Internal
Daniela Neto, Marta Cunha, Filipe Goncalves, Jorge Cotter
Summary: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a common and well-known monogenic small vessel disease caused by a genetic mutation in the NOTCH3 gene. It can manifest in various symptoms and was confirmed in this case report of a 69-year-old man with paresthesias.
CUREUS JOURNAL OF MEDICAL SCIENCE
(2022)
Article
Medicine, General & Internal
Asuman Orhan Varoglu, Begumhan Baysal, Umit Goren
Summary: This case study presents a 63-year-old female patient with clinical features of MS but MRI findings consistent with CADASIL. The patient did not exhibit classic clinical features of CADASIL, and had a positive OCB in the CSF examination. Treatment with IV corticosteroids and azathioprine led to recovery.
CUREUS JOURNAL OF MEDICAL SCIENCE
(2021)
Article
Medicine, General & Internal
Yuya Kano, Ikuko Mizuta, Akihiko Ueda, Hiroaki Nozaki, Keita Sakurai, Osamu Onodera, Yukio Ando, Kentaro Yamada, Hiroyuki Yuasa, Toshiki Mizuno
Summary: A 64-year-old Japanese man with recurrent cerebral ischemic events and cognitive impairment was suspected to have CADASIL due to family history and MRI findings. The identification of a cysteine-sparing variation p.Va1237Met in NOTCH3 raised uncertainty about the definitive diagnosis and pathogenicity of the patient. Additional review of previous reports of two Japanese families with p.Va1237Met was conducted.
Article
Endocrinology & Metabolism
Yingying Gong, Li Xiong, Xiujun Li, Lei Su, Haipeng Xiao
Summary: In this study, a novel heterozygous mutation of WFS1 was identified in a Wolfram syndrome patient, leading to dysregulated ER stress signaling and cell apoptosis. The mutant WFS1 was unable to restore the unfolded protein response and apoptosis induced by WFS1 knockdown. These findings expand the spectrum of WFS1 gene mutations and enhance our understanding of the role of mutant WFS1 in the pathogenesis of WS.
BMC ENDOCRINE DISORDERS
(2021)
Article
Clinical Neurology
Paul Reidler, Alex Brehm, Peter B. Sporns, Vanessa Granja Burbano, Lena Stueckelschweiger, Gabriel Broocks, Thomas Liebig, Marios-Nikos Psychogios, Jens Ricke, Konstantinos Dimitriadis, Martin Dichgans, Wolfgang G. Kunz, Steffen Tiedt
Summary: The study found that human stroke progression varies across the 24-hour cycle, with patients who have nocturnal stroke onset showing larger infarct core volumes and faster core growth. These findings have implications for the design and interpretation of neuroprotection trials.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Meeting Abstract
Clinical Neurology
Marios K. Georgakis, Livia Parodi, Simon Frerich, Ernst Mayerhofer, Rainer Malik, Martin Dichgans, Jonathan Rosand, Chris D. Anderson
Article
Clinical Neurology
Frank Jessen, Steffen Wolfsgruber, Luca Kleineindam, Annika Spottke, Slawek Altenstein, Claudia Bartels, Moritz Berger, Frederic Brosseron, Marcel Daamen, Martin Dichgans, Laura Dobisch, Michael Ewers, Friederike Fenski, Klaus Fliessbach, Silka D. Freiesleben, Wenzel Glanz, Doreen Goerss, Selim Guersel, Daniel Janowitz, Ingo Kilimann, Xenia Kobeleva, Andrea Lohse, Franziska Maier, Coraline Metzger, Matthias Munk, Lukas Preis, Carolin Sanzenbacher, Eike Spruth, Boris Rauchmann, Ruth Vukovich, Renat Yakupov, Anne-Sophie Weyrauch, Gabriel Ziegler, Matthias Schmid, Christoph Laske, Robert Perneczky, Anja Schneider, Jens Wiltfang, Stefan Teipel, Katharina Buerger, Josef Priller, Oliver Peters, Alfredo Ramirez, Henning Boecker, Michael T. Heneka, Michael Wagner, Emrah Duezel
Summary: Research finds that subjective cognitive decline (SCD) in individuals who seek medical help may serve as an initial symptomatic stage 2 of the Alzheimer's disease (AD) continuum. The SCD group shows slightly worse cognition, as well as more subtle functional and behavioral symptoms compared to the control group (CO). It is also discovered that SCD-A+ cases (39.3% of all SCD) exhibit greater hippocampal atrophy, lower cognitive and functional performance, and more behavioral symptoms.
ALZHEIMERS & DEMENTIA
(2023)
Article
Clinical Neurology
Marios K. Georgakis, Rong Fang, Marco Duering, Frank A. Wollenweber, Felix J. Bode, Sebastian Stoesser, Christine Kindlein, Peter Hermann, Thomas G. Liman, Christian H. Nolte, Lucia Kerti, Benno Ikenberg, Kathleen Bernkopf, Holger Poppert, Wenzel Glanz, Valentina Perosa, Daniel Janowitz, Michael Wagner, Katja Neumann, Oliver Speck, Laura Dobisch, Emrah Duezel, Benno Gesierich, Anna Dewenter, Annika Spottke, Karin Waegemann, Michael Goertler, Silke Wunderlich, Matthias Endres, Inga Zerr, Gabor Petzold, Martin Dichgans
Summary: The global burden of small vessel disease (SVD) predicts cognitive and functional outcomes in stroke patients, but the current score used for assessment does not improve prediction capability. Assessing the severity of SVD lesions adds value in predicting outcomes beyond known predictors.
ALZHEIMERS & DEMENTIA
(2023)
Article
Clinical Neurology
Anna Dewenter, Mina A. Jacob, Mengfei Cai, Benno Gesierich, Paul Hager, Anna Kopczak, Davina Biel, Michael Ewers, Anil M. Tuladhar, Frank-Erik De Leeuw, Martin Dichgans, Nicolai Franzmeier, Marco Duering
Summary: Fixel-based analysis of diffusion MRI can identify changes in white matter integrity. Neurodegeneration in Alzheimer's disease affects white matter macrostructure, while cerebral small vessel disease affects white matter microstructure. Fiber density reflects the impact of cerebral small vessel disease, while fiber-bundle cross-section is primarily determined by neurodegeneration.
Article
Endocrinology & Metabolism
Charlotte Dupe, Stephanie Guey, Lucie Biard, Sokhna Dieng, Jessica Lebenberg, Lina Grosset, Nassira Alili, Dominique Herve, Elisabeth Tournier-Lasserve, Eric Jouvent, Sylvie Chevret, Hugues Chabriat
Summary: The prevalence of cysteine mutations in the NOTCH3 gene responsible for CADASIL was found to be more than 100 times higher in the general population than in patients. The mutation location in the EGFr-like domains of the NOTCH3 receptor has a major impact on the clinical severity and imaging features of the disease. The exact mechanisms underlying the effects of mutation location on the disease still need to be determined.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2023)
Article
Clinical Neurology
Silvia Lanfranconi, Elisa Scola, Jennifer M. T. A. Meessen, Roberto Pallini, Giulio A. Bertani, Rustam Al-Shahi Salman, Elisabetta Dejana, Roberto Latini, Treat CCM Investigators
Summary: Background observations and preclinical models suggest that prolonged treatment with propranolol may reduce the risk of intracerebral hemorrhage in patients with familial cerebral cavernous malformations. A phase 2 pilot trial was conducted to evaluate the safety and efficacy of propranolol in reducing the incidence of symptomatic intracerebral hemorrhage or focal neurological deficit in this patient population.
Article
Clinical Neurology
Joan Marti-Fabregas, Pol G. Camps-Renom, Jonathan G. Best, Anna Ramos-Pachon, Marina Guasch-Jimenez, Alejandro Martinez-Domeno, Daniel M. Guisado-Alonso, Beatriz M. Gomez-Anson, Gareth Ambler, Duncan Wilson, Keon-Joo Lee, Jae-Sung Lim, Hee-Joon Bae, Masayuki Shiozawa, Masatoshi Koga, Kazunori G. Toyoda, Michael G. Hennerici, Hugues Chabriat, Eric Jouvent, Debbie Yuen Kwun Wong, Henry Mak, Kui Kai Lau, Young Dae Kim, Tae-Jin Song, Ji-Hoe Heo, Sebastian Eppinger, Thomas Gattringer, Ender Uysal, Derya Selcuk Demirelli, Natan Bornstein, Einor Ben Assayag, Hen A. Hallevi, Jeremy A. Molad, Masashi Nishihara, Jun Tanaka, Hideo Hara, Yusuke B. Yakushiji, Shelagh B. Coutts, Eric A. Smith, Alexandros A. Polymeris, Benjamin Wagner, David A. Seiffge, Philippe A. Lyrer, Nils T. Peters, Stefan T. Engelter, Rustam Al-Shahi Salman, Hans Rudolf Jager, Gregory Y. H. Lip, Martina Goeldlin, Leonidas Panos, Christopher Charles G. Karayiannis, Thanh G. K. Phan, Velandai K. Srikanth, Nicolas Christ, Sarah Gunkel, Felix W. Fluri, Thomas W. Leung, Yannie O. Y. Soo, Winnie Chu, Jill Abrigo, Carmen Barbato, Simone Browning, Robert Simister, Anne-Marie Mendyk, Regis Bordet, Saima Hilal, Bibek Gyanwali, Christopher Chen, Simon Jung, Dilek Necioglu Orken, David Werring, Luis Prats-Sanchez
Summary: This study aimed to investigate the risk of future cerebrovascular events in patients with ischemic stroke (IS) or transient ischemic attack (TIA) and cortical superficial siderosis (cSS), as well as the benefits and safety of antithrombotic drugs for secondary prevention. The study found that cSS was associated with an increased risk of stroke, and the risk of IS was higher than that of intracranial hemorrhage (ICrH) in patients receiving antiplatelet or anticoagulant treatment alone, while the risk of ICrH was higher than that of IS in patients receiving both treatments. Therefore, the study suggests that using antiplatelet or anticoagulant drugs alone is safe in patients with cSS, but combined antithrombotic therapy might be hazardous.
Article
Clinical Neurology
S. Reyes, A. Jabouley, N. Alili, M. H. De Sanctis, C. Machado, A. Taleb, D. Herve, N. Dias-Gastellier, H. Chabriat
Summary: The study aimed to investigate the psychological impact of COVID-19 containment measures on CADASIL patients. The results showed that only 9% of patients experienced depressive symptoms, and the occurrence of stressor-related disorder was associated with socio-environmental factors such as living alone, unemployment, and having multiple children at home.
JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Elisa Ouin, Ana Dimitrovic, Lina Grosset, Jessica Lebenberg, Antoine Guillonnet, Jean-Pierre Guichard, Dominique Herve, Hugues Chabriat, Eric Jouvent
Summary: In CADASIL, WMHCC are likely due to secondary degeneration, cross nearby lacunes, and are independently associated with clinical severity, in contrast to the total burden of WMH.
Article
Clinical Neurology
Valerie Krivosic, Michel Paques, Dominique Herve, Cedric Duliere, Abbas Taleb, Nathalie Gastellier, Eric Jouvent, Jessica Lebenberg, Ramin Tadayoni, Hugues Chabriat
Summary: In patients with CADASIL, retinal vascular density (VD) decreases with age but does not appear to be related to the severity of clinical or imaging manifestations.
BMJ NEUROLOGY OPEN
(2023)
Editorial Material
Cardiac & Cardiovascular Systems
Martin Dichgans, Frank M. Faraci, Christer Betsholtz, Elizabeth Hillman, Anne Joutel, Mark Nelson, Dominik Paquet, BRENDA Network
EUROPEAN HEART JOURNAL
(2023)
Article
Neuroimaging
Marco Egle, Saima Hilal, Anil M. Tuladhar, Lukas Pirpamer, Steven Bell, Edith Hofer, Marco Duering, James Wason, Robin G. Morris, Martin Dichgans, Reinhold Schmidt, Daniel J. Tozer, Thomas R. Barrick, Christopher Chen, Frank -Erik de Leeuw, Hugh S. Markus
Summary: This study evaluated different DTI analysis strategies in SVD and found that all the analyzed methods predicted dementia. PSMD, as a fully automated analysis method, offered advantages for large datasets.
NEUROIMAGE-CLINICAL
(2022)