Article
Genetics & Heredity
Sara Biagiotti, Ambra Barone, Mattia Paolo Aliano, Giulia Federici, Marco Malatesta, Caterina Caputi, Silvia Soddu, Vincenzo Leuzzi, Luciana Chessa, Mauro Magnani
Summary: Most ATM variants associated with Ataxia Telangiectasia are classified as variants with uncertain significance. This study focused on a specific ATM variant found in Lebanese brothers, revealing it to be pathogenic even though it causes an atypical phenotype. Dexamethasone showed therapeutic potential on this and possibly other missense ATM variants.
FRONTIERS IN GENETICS
(2021)
Review
Biochemistry & Molecular Biology
Goutham Narayanan Subramanian, Abrey Jie Yeo, Magtouf Hnaidi Gatei, David John Coman, Martin Francis Lavin
Summary: The ATM protein kinase has diverse functions in the cell, including protecting DNA, maintaining cellular homeostasis, and safeguarding against external and internal damage.
Article
Biology
Dandan Yao, Qingyuan He, Shangyin Bai, Hang Zhao, Jun Yang, Dehua Cui, Yan Yu, Xuechao Fei, Yufei Mei, Ye Cheng, Shi Yan, Nayan Huang, Yalan Di, Xianjie Cai, Rui Wang, Yajuan Gao, Fangrao Cheng, Shengjie Zhao, Xu Yang, Xiang Cai, Hongbin Han, Jihui Lyu, Zhiqian Tong
Summary: Accumulation of formaldehyde in both muscle and cerebellum contributes to motor deficits in a mouse model of hindlimb unloading. Scavenging formaldehyde may be a useful treatment to limit motor dysfunction following limb offloading conditions.
COMMUNICATIONS BIOLOGY
(2021)
Article
Genetics & Heredity
Boxun Zhao, Minh A. Nguyen, Sijae Woo, Jinkuk Kim, Timothy W. Yu, Eunjung Alice Lee
Summary: This study conducted retroelement profiling on whole-genome sequencing data from 237 individuals with ataxia telangiectasia (A-T), and found retroelement insertions in the ATM gene in 15 individuals. Most of the insertions were located in noncoding regions, and 12 intronic insertions led to ATM loss of function. The study also presented proof-of-concept antisense oligonucleotides that can suppress cryptic exonization caused by deep intronic retroelement insertion.
AMERICAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Clinical Neurology
Marius Theis, Helena Donath, Sandra Woelke, Shahrzad Bakhtiar, Emilia Salzmann-Manrique, Stefan Zielen, Matthias Kieslich
Summary: This study aimed to evaluate peripheral neurodegeneration and age-dependent neuropathy development in A-T patients through neurophysiological measurements. The findings revealed that neuropathic changes can be observed as early as the first year of life in A-T patients, although subjective symptoms are rarely reported. Motor neuropathy in the upper extremities was predominantly of a demyelinating type, while sensory neuropathy was predominantly of a mixed type. In the lower extremities, both motor and sensory neuropathy were predominantly of a mixed type. Age was found to have a significant correlation with the development of motor and sensory polyneuropathy in A-T patients compared to healthy controls.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Rebecca Presterud, Wei Hai Deng, Anna Berit Wennerstrom, Trudy Burgers, Bharat Gajera, Kirsten Mattsson, Agnes Solberg, Evandro F. Fang, Anni I. Nieminen, Asbjorg Stray-Pedersen, Hilde Nilsen
Summary: Long-term supplementation of nicotinamide riboside (NR) appears to be safe and well tolerated in patients with ataxia telangiectasia (A-T), and it improves motor coordination and eye movements.
MOVEMENT DISORDERS
(2023)
Review
Health Care Sciences & Services
Sharon A. McGrath-Morrow, Cynthia C. Rothblum-Oviatt, Jennifer Wright, Haley Schlechter, Maureen A. Lefton-Greif, Valerie A. Natale, Thomas O. Crawford, Howard M. Lederman
Summary: Ataxia telangiectasia (A-T) is a rare autosomal recessive disease characterized by progressive ataxia, oculocutaneous telangiectasias, and immune system impairment. Patients with A-T have an increased risk of malignancy, leading to premature death.
JOURNAL OF MULTIDISCIPLINARY HEALTHCARE
(2021)
Article
Biochemistry & Molecular Biology
Jakub Czarny, Marta Andrzejewska, Olga Zajac-Spychala, Elzbieta Latos-Grazynska, Agata Pastorczak, Kamila Wypyszczak, Aleksandra Szczawinska-Poplonyk, Izabela Niewiadomska-Wojnalowicz, Agnieszka Wziatek, Patrycja Marciniak-Stepak, Michal Dopierala, Jadwiga Maldyk, Katarzyna Jonczyk-Potoczna, Katarzyna Derwich
Summary: Ataxia-telangiectasia (AT) is a rare genetic disorder characterized by DNA repair defect, chromosomal instability, and hypersensitivity to radiation. Successful clinical management of patients with AT is challenging due to poor treatment response, high toxicity, and the need to avoid radiation exposure. This case report describes a 7-year-old female patient with AT and LBCL with IRF4 rearrangement who achieved a favorable outcome through treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Rudel A. Saunders, Thomas F. Michniacki, Courtney Hames, Hilary A. Moale, Carol Wilke, Molly E. Kuo, Johnathan Nguyen, Andrea J. Hartlerode, Bethany B. Moore, JoAnn M. Sekiguchi
Summary: Ataxia-telangiectasia (A-T) is a multisystem disorder with lung complications as a major cause of mortality. This study demonstrates the significant role of ATM-deficient immune cells in causing lung pathologies in A-T, and suggests that targeted inhibition of aberrant inflammatory responses could be a viable therapeutic strategy for A-T lung disease.
SCIENTIFIC REPORTS
(2021)
Article
Genetics & Heredity
B. Dalmasso, L. Pastorino, V Nathan, N. N. Shah, J. M. Palmer, M. Howlie, P. A. Johansson, N. D. Freedman, B. D. Carter, L. Beane-Freeman, B. Hicks, A. Molven, H. Helgadottir, A. Sankar, H. Tsao, A. J. Stratigos, P. Helsing, R. Van Doorn, N. A. Gruis, M. Visser, K. A. W. Wadt, G. Mann, E. A. Holland, E. Nagore, M. Potrony, S. Puig, C. Menin, K. Peris, M. C. Fargnoli, D. Calista, N. Soufir, M. Harland, T. Bishop, P. A. Kanetsky, D. E. Elder, V Andreotti, I Vanni, W. Bruno, V Hoiom, M. A. Tucker, X. R. Yang, P. A. Andresen, D. J. Adams, M. T. Landi, N. K. Hayward, A. M. Goldstein, P. Ghiorzo
Summary: This study supports the role of ATM as a melanoma predisposition gene, with LOF variants suggesting a moderate-risk.
GENETICS IN MEDICINE
(2021)
Article
Biology
Harvey Perez, May F. Abdallah, Jose Chavira, Angelina S. Norris, Martin T. Egeland, Karen L. Vo, Callan L. Buechsenschuetz, Valentina Sanghez, Jeannie L. Kim, Molly Pind, Kotoka Nakamura, Geoffrey G. Hicks, Richard A. Gatti, Joaquin Madrenas, Michelina Iacovino, Peter J. McKinnon, Paul J. Mathews
Summary: By introducing null mutations in both the Atm and Aptx genes in mice, researchers have created a novel mouse model that exhibits progressively severe ataxic phenotype and cerebellar molecular layer atrophy. The perturbations significantly alter the biophysical properties of cerebellar Purkinje neurons and their neural activity, correlating with cerebellar atrophy and ataxia over the animal's first year of life. Additionally, the double mutant mice also show a predisposition to cancer and immune abnormalities, resembling symptoms of A-T.
Article
Immunology
Geraldine Blanchard-Rohner, Anna Peirolo, Ludivine Coulon, Christian Korff, Judit Horvath, Pierre R. Burkhard, Fabienne Gumy-Pause, Emmanuelle Ranza, Peter Jandus, Harpreet Dibra, Alexander Malcolm R. Taylor, Joel Fluss
Summary: Ataxia-telangiectasia (A-T) is a neurodegenerative and primary immunodeficiency disorder characterized by various symptoms. This study presents a case series highlighting the phenotypic variability of A-T and emphasizes the importance of early diagnosis of variant A-T and classical A-T.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Ruth Pia Duecker, Lucia Gronau, Patrick C. Baer, Stefan Zielen, Ralf Schubert
Summary: Our study focused on investigating the feasibility of different approaches of hematopoietic stem cell transplantation (HSCT) for Ataxia-telangiectasia (A-T) by using Atm-deficient mice as models. The results showed that haploidentical HSCT could extend the lifespan of Atm-deficient mice and improve T-cell numbers and functionality. Interestingly, HSCT using heterozygous donor cells also led to improved survival and enhanced CD4 cell functionality in Atm-deficient mice, suggesting it as a potential strategy for A-T treatment.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Sapir Schlam-Babayov, Ariel Bensimon, Michal Harel, Tamar Geiger, Ruedi Aebersold, Yael Ziv, Yosef Shiloh
Summary: This study conducted a comprehensive phosphoproteomic analysis in human wild-type and A-T cells to reveal the fine-tuned dynamics and relationships between PIKKs in the response to genotoxic stress. The results highlight the complex interactions among ATM, ATR, and DNA-PK in the DDR.
Review
Cell Biology
Venturina Stagni, Alessandra Ferri, Claudia Cirotti, Daniela Barila
Summary: There is a strong interplay between autophagy and genomic stability, with recent evidence linking DNA Damage Response (DDR) and autophagy in influencing cell fate. ATM kinase plays a crucial role in balancing senescence and apoptosis in response to stimuli, and its aberrant deregulation is linked to the development of pathologies like cancer and neurodegeneration.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Neurosciences
Jing Tian, Jorge Otero-Millan, David S. Zee, Amir Kheradmand
Summary: This study presents a case of spontaneous upbeat nystagmus (UBN) caused by an ischemic lesion in the paramedian tract (PMT) of the medulla. Eye movement recordings showed that the slow phase of the nystagmus initially decreased in velocity but gradually increased. Simulation using a mathematical model suggests that the PMT plays a role in transmitting premotor signals for vertical gaze holding to the cerebellum.
Article
Neurosciences
Hassen Kerkeni, David S. Zee, Athanasia Korda, Miranda Morrison, Georgios Mantokoudis, Stefano Ramat
Summary: When the demands for visual stabilization exceed the ability of the vestibuloocular reflex (VOR) to compensate, the brain produces corrective saccades known as covert saccades. The triggers and role of prediction in generating covert saccades are still unknown. In a study of patients with acute vestibular neuritis, predictable stimuli led to higher VOR gain, smaller gaze error, and earlier occurrence of covert corrective saccades.
JOURNAL OF NEUROPHYSIOLOGY
(2023)
Article
Clinical Neurology
Seung-Han Lee, Jae-Myung Kim, Joon-Tae Kim, Alexander Andrea Tarnutzer
Summary: This study retrospectively analyzed 6 patients with isolated (hemi)nodular strokes and conducted comprehensive neuro-otological assessments. The study found that the patients had normal horizontal and vertical vestibulo-ocular reflex (aVOR) function but exhibited various ocular motor abnormalities and postural control issues.
FRONTIERS IN NEUROLOGY
(2023)
Article
Ophthalmology
Chen Wang, Yunong Bai, Ashley Tsang, Yuhan Bian, Yifan Gou, Yan X. Lin, Matthew Zhao, Tony Y. Wei, Jacob M. Desman, Casey Overby Taylor, Joseph L. Greenstein, Jorge Otero-Millan, Tin Yan Alvin Liu, Amir Kheradmand, David S. Zee, Kemar E. Green
Summary: The purpose of this study was to develop deep learning models using synthetic fundus images to assess static ocular torsion. The models achieved high accuracy and area under the receiver operating characteristic curve (AUROC) on both synthetic and nonsynthetic datasets, demonstrating their potential for clinical use. This research has important implications for diagnosing and classifying vertical ocular misalignment.
TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
(2023)
Article
Clinical Neurology
Alexander A. Tarnutzer, Daniel Gold, Zheyu Wang, Karen A. Robinson, Jorge C. Kattah, Georgios Mantokoudis, Ali S. Saber Tehrani, David S. Zee, Jonathan A. Edlow, David E. Newman-Toker
Summary: This study assessed the accuracy of bedside findings in differentiating peripheral vestibular from central neurologic causes. The HINTS eye movement battery had high sensitivity and specificity for stroke diagnosis. These findings suggest that HINTS examination should be disseminated to all clinicians evaluating dizziness/vertigo.
ANNALS OF NEUROLOGY
(2023)
Article
Medicine, General & Internal
Urs Fischer, Masatoshi Koga, Daniel Strbian, Mattia Branca, Stefanie Abend, Sven Trelle, Maurizio Paciaroni, Goetz Thomalla, Patrik Michel, Krassen Nedeltchev, Leo H. Bonati, George Ntaios, Thomas Gattringer, Else-Charlotte Sandset, Peter Kelly, Robin Lemmens, P. N. Sylaja, Diana Aguiar de Sousa, Natan M. Bornstein, Zuzana Gdovinova, Takeshi Yoshimoto, Marjaana Tiainen, Helen Thomas, Manju Krishnan, Gek C. Shim, Christoph Gumbinger, Jochen Vehoff, Liqun Zhang, Kosuke Matsuzono, Espen Kristoffersen, Philippe Desfontaines, Peter Vanacker, Angelika Alonso, Yusuke Yakushiji, Caterina Kulyk, Dimitri Hemelsoet, Sven Poli, Ana Paiva Nunes, Nicoletta Caracciolo, Peter Slade, Jelle Demeestere, Alexander Salerno, Markus Kneihsl, Timo Kahles, Daria Giudici, Kanta Tanaka, Silja Raty, Rea Hidalgo, David J. Werring, Martina Goldlin, Marcel Arnold, Cecilia Ferrari, Seraina Beyeler, Christian Fung, Bruno J. Weder, Turgut Tatlisumak, Sabine Fenzl, Beata Rezny-Kasprzak, Arsany Hakim, Georgia Salanti, Claudio Bassetti, Jan Gralla, David J. Seiffge, Thomas Horvath, Jesse Dawson
Summary: This study aimed to compare the effect of early initiation versus later initiation of direct oral anticoagulants (DOACs) on acute ischemic stroke in patients with atrial fibrillation. The results showed that there was no significant difference in the incidence of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death within 30 days between early and later use of DOACs.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Review
Clinical Neurology
Martina Wuthrich, Zheyu Wang, Carlos Mario Martinez, Sergio Carmona, Georgios Mantokoudis, Alexander Andrea Tarnutzer
Summary: This study assessed the patterns of spontaneous nystagmus (SN) in patients with acute prolonged vertigo and its diagnostic accuracy at the bedside. The findings showed that horizontal or horizontal-torsional SN was more often observed in peripheral AVS (pAVS) patients, while torsional and/or vertical SN patterns were more prevalent in central AVS (cAVS) patients. For central causes, the presence of isolated vertical/vertical-torsional SN or isolated torsional SN had high specificity but low sensitivity. The absence of any horizontal SN was more frequently seen in cAVS than in pAVS.
FRONTIERS IN NEUROLOGY
(2023)
Article
Clinical Neurology
Simone Hemm, Denise Baumann, Vasco Duarte da Costa, Alexander Andrea Tarnutzer
Summary: The Fukuda-stepping-test (FST) is proposed as a method to assess the integrity of the vestibular pathways. This study found individual differences in the test performance, which may be due to variations in the macular organs and central processing of vestibular input. Using an IMU-based approach, additional dynamic parameters could be retrieved, providing useful information for distinguishing patients from healthy controls.
FRONTIERS IN NEUROLOGY
(2023)
Article
Clinical Neurology
Norbert Silimon, Boudewijn Drop, Leander Clenin, Krassen Nedeltchev, Timo Kahles, Alexander A. Tarnutzer, Mira Katan, Leo Bonati, Stephan Salmen, Sylvan Albert, Alexander Salerno, Emmanuel Carrera, Christian Berger, Nils Peters, Friedrich Medlin, Carlo Cereda, Manuel Bolognese, Georg Kaegi, Susanne Renaud, Julien Niederhauser, Christophe Bonvin, Michael Schaerer, Marie-Luise Mono, Andreas Luft, Biljana Rodic-Tatic, Urs Fischer, Simon Jung, Marcel Arnold, Thomas Meinel, David Seiffge
Summary: This study investigated the frequency, potential causes, and outcomes of ischaemic stroke in patients despite antiplatelet therapy (APT). It was found that one-third of patients experienced stroke while on APT, and 20% of patients with a history of stroke did not receive antithrombotic therapy during stroke recurrence. These patients with breakthrough strokes despite APT are at an increased risk of recurrent stroke.
EUROPEAN STROKE JOURNAL
(2023)
Article
Clinical Neurology
Maritta Spiegelberg, Ekin Ermis, Andreas Raabe, Alexander Andrea Tarnutzer
Summary: A rare case of triggered episodic vestibular syndrome accompanied by transient loss of consciousness caused by retrostyloidal vagal schwannoma is described. The patient experienced nausea, dysphagia, and odynophagia triggered by swallowing food, resulting in weight loss and an inability to work. Treatment with radiosurgery showed reduction of symptoms.
FRONTIERS IN NEUROLOGY
(2023)
Editorial Material
Clinical Neurology
Alexander Andrea Tarnutzer, Toru Seo, Chisato Fujimoto, Dominik Straumann, Toshihisa Murofushi
FRONTIERS IN NEUROLOGY
(2023)
Review
Neurosciences
Pilar Garces, Chrystalina A. Antoniades, Anna Sobanska, Norbert Kovacs, Sarah H. Ying, Anoopum S. Gupta, Susan Perlman, David J. Szmulewicz, Chiara Pane, Andrea H. Nemeth, Laura B. Jardim, Giulia Coarelli, Michaela Dankova, Andreas Traschuetz, Alexander A. Tarnutzer
Summary: Oculomotor deficits in hereditary ataxia are often neglected in clinical ataxia scales and outcome measures for trials. However, quantitative assessment of oculomotor function is now more available and applicable in multicenter trials. Based on a literature review, this consensus paper proposes a standardized methodology for assessing oculomotor function in hereditary ataxia and provides guidelines for data extraction. Standardization of oculomotor assessments will advance our understanding of oculomotor dysfunction in hereditary ataxias.
Article
Neurosciences
Pilar Garces, Chrystalina A. Antoniades, Anna Sobanska, Norbert Kovacs, Sarah H. Ying, Anoopum S. Gupta, Susan Perlman, David J. Szmulewicz, Chiara Pane, Andrea H. Nemeth, Laura B. Jardim, Giulia Coarelli, Michaela Dankova, Andreas Traschuetz, Alexander A. Tarnutzer
Summary: Characterizing bedside oculomotor deficits is important in understanding hereditary ataxias. Quantitative assessments provide advantages in monitoring disease progression and treatment response. This study identifies the potential of quantitative oculomotor assessments as outcome measures for clinical trials in specific ataxia genotypes.
Review
Audiology & Speech-Language Pathology
Alexander A. Tarnutzer, Jonathan A. Edlow
Summary: Acute vertigo and dizziness are common presenting symptoms in the emergency department and can be caused by various conditions. Algorithms incorporating structured history taking and subtle oculomotor signs have high diagnostic accuracy, while other approaches relying on vascular risk factors and clinical symptoms have lower accuracy.
AUDIOLOGY RESEARCH
(2023)
