Review
Clinical Neurology
Philippe Corcia, Christian Lunetta, Patrick Vourc'h, Pierre-Francois Pradat, Helene Blasco
Summary: This article reviews the progress in the diagnosis, monitoring, and treatment of amyotrophic lateral sclerosis (ALS). Despite the difficulty in diagnosing and the lack of a cure for ALS, there is evidence to suggest that an optimistic view of ALS management in the coming years is now realistic.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Fei Mao, John L. Robinson, Travis Unger, Marijan Posavi, Defne A. Amado, Lauren Elman, Murray Grossman, David A. Wolk, Edward B. Lee, Vivianna M. Van Deerlin, Silvia Porta, Virginia M. Y. Lee, John Q. Trojanowski, Alice S. Chen-Plotkin
Summary: The study revealed that genotypes at the TMEM106B locus and hexanucleotide repeat expansions in C9orf72 were associated with the severity and regional distribution of TDP-43 pathology in neurodegenerative diseases. While C9orf72 expansions were linked to greater TDP-43 pathology in ALS, the relationship between TMEM106B genotype and TDP-43 pathology remained consistent. Manipulating TMEM106B levels showed a causal role in modifying the development of TDP-43 proteinopathy.
ACTA NEUROPATHOLOGICA
(2021)
Review
Medicine, General & Internal
Eva Parobkova, Radoslav Matej
Summary: ALS is a progressive and devastating disorder that overlaps clinically with FTLD. While many gene mutations are known to cause ALS, how they selectively impact motor neuron biology and whether they converge on common pathways remains poorly understood.
Article
Health Care Sciences & Services
Izaro Kortazar-Zubizarreta, Africa Manero-Azua, Juan Afonso-Aguera, Guiomar Perez de Nanclares
Summary: The expanded GGGGCC hexanucleotide repeat in the C9ORF72 gene is the most common genetic cause of familial forms of ALS, FTD, and ALS-FTD. This study describes the clinical-genetic findings in a Basque family and provides a narrative review of the main features associated with C9ORF72-HRE. The study highlights the challenge of medication development due to the clinical variability of C9ORF72-HRE.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Review
Clinical Neurology
Srestha Mazumder, Matthew C. Kiernan, Glenda M. Halliday, Hannah C. Timmins, Colin J. Mahoney
Summary: Considerable efforts have been made to understand fatal neurodegenerative diseases like ALS through postmortem brain tissues from brain banks. This review summarizes the influence of brain banks on ALS research, correlates the location of brain banks with ALS prevalence, identifies reported features from postmortem studies, and proposes common reporting standards. The genetics of ALS and protein pathology were the primary focus, and the majority of brain banks were located in Europe and North America. There is a strong need for standardized reporting in this field.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2022)
Article
Clinical Neurology
Lu Tang, Lu Chen, Xiaolu Liu, Ji He, Yan Ma, Nan Zhang, Dongsheng Fan
Summary: A study found that a repeat length of 2 in the C9orf72 gene may be associated with better survival in ALS patients without C9orf72 repeat expansions, while the repeat length of the ATXN2 gene does not have a significant impact. Age of onset, diagnostic delay, and carrying the C9orf72 repeat length of 2 were found to influence the survival of patients without C9orf72 repeat expansions, with bulbar onset being associated with poorer survival when patients carried a maximum C9orf72 repeat allele over 2.
FRONTIERS IN NEUROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yixin Wang, Liu Liu, Hui Chen, Yinxue Yang, Chenchen Mu, Haigang Ren, Yanli Liu, Liqiang Yu, Qi Fang, Guanghui Wang, Zongbing Hao
Summary: This study identified severe DNA damage caused by poly-PR and its interaction with the ALS-related FUS protein, suggesting a potential therapeutic role of FUS in alleviating poly-PR-induced cell toxicity.
HUMAN MOLECULAR GENETICS
(2023)
Article
Neurosciences
Cassandra N. Dennys, Florence Roussel, Rochelle Rodrigo, Xiaojin Zhang, Andrea Sierra Delgado, Annalisa Hartlaub, Asya Saelim-Ector, Will Ray, Sarah Heintzman, Ashley Fox, Stephen J. Kolb, Joseph Beckman, Maria Clara Franco, Kathrin Meyer
Summary: Patient diversity and unknown disease cause pose challenges for drug development and clinical trial design in ALS. Reprogramming patient fibroblasts to neuronal progenitor cells can generate disease relevant cell types for compound testing. CuATSM, currently in clinical trial for ALS, showed a differential effect on neuronal survival in co-culture assays. Elevated mitochondrial respiration was observed in all CuATSM-responders, suggesting a potential metabolic mechanism for CuATSM's therapeutic effects.
Article
Biochemistry & Molecular Biology
Shanez Haouari, Christian Robert Andres, Debora Lanznaster, Sylviane Marouillat, Celine Brulard, Audrey Dangoumau, Devina Ung, Charlotte Veyrat-Durebex, Frederic Laumonnier, Helene Blasco, Philippe Couratier, Philippe Corcia, Patrick Vourc'h
Summary: Using next-generation sequencing, pathogenic variants in genes of the ubiquitin pathway were identified in ALS patients, including known genes FUS, CCNF, and UBQLN2, as well as new genes such as HECW1. Overexpression of NEDL1, a protein encoded by HECW1, was found to be associated with increased cell death and mislocalization of TDP-43. These findings provide further evidence for the involvement of the ubiquitin pathway in ALS and suggest the need for further investigation of the HECW1 gene and NEDL1 in ALS pathophysiology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Geriatrics & Gerontology
Suzanna Edgar, Melina Ellis, Nur Adilah Abdul-Aziz, Khean-Jin Goh, Nortina Shahrizaila, Marina L. Kennerson, Azlina Ahmad-Annuar
Summary: This study identified mutations in SOD1 and C9orf72 genes in a multi-ethnic Malaysian ALS cohort, with a mutation frequency of 5.9%. No mutations were found in FUS and TARDBP genes. Further investigation is needed to uncover novel genes and disease pathways in ALS.
NEUROBIOLOGY OF AGING
(2021)
Article
Neurosciences
Kyle J. Trageser, Eun-Jeong Yang, Chad Smith, Ruth Iban-Arias, Tatsunori Oguchi, Maria Sebastian-Valverde, Umar Haris Iqbal, Henry Wu, Molly Estill, Md Al Rahim, Urdhva Raval, Francis J. Herman, Yong Jie Zhang, Leonard Petrucelli, Giulio Maria Pasinetti
Summary: Hexanucleotide repeat expansions in C9orf72 gene cause frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS) and lead to the production of toxic dipeptide repeat (DPR) proteins, with poly(glycine-arginine) (GR) being the most toxic and accumulating in relevant brain regions. Neuroinflammation is a driving factor in the disease, and increased inflammasome-mediated neuroinflammation is observed in C9orf72 FTD/ALS mice, suggesting a role for HRE in innate immunity and the NLRP3 inflammasome as a potential therapeutic target.
MOLECULAR NEUROBIOLOGY
(2023)
Review
Cell Biology
Mehdi Ghasemi, Kiandokht Keyhanian, Catherine Douthwright
Summary: The understanding of immune system dysregulation and glial cell dysfunction in C9orf72 ALS/FTD, along with the pathologic hallmarks and toxicities of C9orf72 glial cells, have shed light on potential therapeutic targets for these diseases.
Article
Cell Biology
Patricia Gomez-Suaga, Gabor M. Morotz, Andrea Markovinovic, Sandra M. Martin-Guerrero, Elisavet Preza, Natalia Arias, Keith Mayl, Afra Aabdien, Vesela Gesheva, Agnes Nishimura, Ambra Annibali, Younbok Lee, Jacqueline C. Mitchell, Selina Wray, Christopher Shaw, Wendy Noble, Christopher C. J. Miller
Summary: This study reveals that hexanucieotide repeat expansions in C9orf72 disrupt the ER-mitochondria signalling and VAPB-PTPIP51 tethers, leading to neurotoxicity. The interaction between VAPB-PTPIP51 is disrupted by neurotoxic DPRs, potentially involving the activation of GSK3β. Furthermore, these DPRs also disrupt the delivery of Ca2+ from ER stores to mitochondria, which is a primary function of the VAPB-PTPIP51 tethers. These findings identify a new molecular target for mutant C9orf72-mediated toxicity.
Review
Pharmacology & Pharmacy
Yutaka Nakagawa, Shizuo Yamada
Summary: ALS is a progressive neurodegenerative disorder characterized by motor dysfunctions resulting from the loss of upper and lower motor neurons. The imbalance of metals and mitochondrial dysfunction may play a key role in the initiation and progression of ALS symptoms, affecting both motor and extra-motor functions.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Review
Geriatrics & Gerontology
Anna Konopka, Julie D. Atkin
Summary: DNA damage and defective DNA repair play an important role in the pathogenesis of amyotrophic lateral sclerosis (ALS). The number of DNA damage or repair proteins linked to ALS is steadily growing, providing new directions for ALS research and treatment.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Review
Ophthalmology
Ghazi Bou Ghanem, Piergiorgio Neri, Rosa Dolz-Marco, Thomas Albini, Amani Fawzi
Summary: Inflammatory choroidal neovascularization (iCNV) is a rare complication of uveitis and can cause vision compromise. Fluorescein angiography (FA) is the gold standard for diagnosis, but it can be difficult to distinguish iCNV from inflammatory lesions. Optical coherence tomography (OCT) is a noninvasive imaging modality that can assist in diagnosing iCNV. OCT angiography (OCTA) uses motion contrast to visualize flow and is useful in distinguishing iCNV from inflammatory lesions. However, further studies are needed to determine its role in evaluating iCNV activity and treatment response.
OCULAR IMMUNOLOGY AND INFLAMMATION
(2023)
Article
Clinical Neurology
Yin A. Liu, Louise A. Mesentier-Louro, Mohammad A. Shariati, Heather E. Moss, Shannon J. Beres, Yaping Joyce Liao
Summary: This study retrospectively reviewed the cases of 5 patients with high-altitude-associated nonarteritic anterior ischemic optic neuropathy (HA-NAION). The study found that high-altitude exposure is a risk factor for HA-NAION, which typically occurs at a younger age and exhibits a progressive course of vision loss after the initial onset. Treatment for obstructive sleep apnea is recommended, especially for patients with repeated high-altitude exposure.
JOURNAL OF NEURO-OPHTHALMOLOGY
(2023)
Article
Clinical Neurology
Heather E. Moss, Kevin E. Lai, Melissa W. Ko
Summary: This study assessed the utilization of telehealth in neuro-ophthalmology during the first year of the COVID-19 pandemic. The results showed that the proportion of neuro-ophthalmologists using video visits remained elevated compared to pre-pandemic levels. Participants identified both benefits and barriers to telemedicine.
JOURNAL OF NEURO-OPHTHALMOLOGY
(2023)
Article
Clinical Neurology
Jason Fan, Rui Tang, Lily Zhang, Phuong T. Hoang, Folusakin Ayoade, Julio A. Diaz-Perez, Heather E. Moss, Hong Jiang
Summary: This article reports two cases of extraparenchymal neurocysticercosis, a rare manifestation of the disease involving the subarachnoid, meningeal, and intraventricular spaces. The diagnosis and treatment of this condition are challenging and require a multidisciplinary approach.
JOURNAL OF NEURO-OPHTHALMOLOGY
(2023)
Article
Clinical Neurology
Elena A. Muro-Fuentes, Sylvia E. Villarreal Navarro, Heather E. Moss
Summary: The accuracy of ICD codes for identifying aON is low, and it is only slightly better when combined with MRI results within 2 months. Positive MRI results can help improve the accuracy of identifying aON cases.
JOURNAL OF NEURO-OPHTHALMOLOGY
(2023)
Article
Ophthalmology
Janice X. Ong, Nicholas Konopek, Hisashi Fukuyama, Amani A. Fawzi
Summary: Capillary nonperfusion parameters on OCTA can predict the development of clinically significant outcomes in eyes with referable NPDR. Deep capillary nonperfusion at baseline is associated with short-term DR complications, indicating its important role in DR progression.
OPHTHALMOLOGY RETINA
(2023)
Article
Ophthalmology
Andrew A. Shen, Karen G. Gutierrez, Natacha C. Villegas, Heather E. Moss
Summary: This study compared disparities in outpatient ophthalmic care during the early and later stages of the COVID-19 pandemic. The results showed that there were differences during the early stage, but one year later, the care returned to the pre-pandemic baseline.
OPHTHALMIC EPIDEMIOLOGY
(2023)
Editorial Material
Ophthalmology
Bonnie B. Huang, Amani A. Fawzi
Article
Ophthalmology
Nicole L. Decker, Brandon V. Duffy, Ghazi O. Boughanem, Hisashi Fukuyama, Daniela Castellanos Canales, Peter L. Nesper, Manjot K. Gill, Amani A. Fawzi
Summary: This study evaluated the correlation between nonperfusion parameters on OCTA and UWF-FA in diabetic subjects. The results showed that OCTA and UWF-FA had comparable performance in detecting clinically referable diabetic retinopathy.
OPHTHALMOLOGY RETINA
(2023)
Article
Ophthalmology
John J. Chen, Eoin P. Flanagan, Sean J. Pittock, Nicole Caroline Stern, Nanthaya Tisavipat, M. Tariq Bhatti, Kevin D. Chodnicki, Deena A. Tajfirouz, Sepideh Jamali, Amy Kunchok, Eric R. Eggenberger, Marie A. Di Nome, Elias S. Sotirchos, Eleni S. Vasileiou, Amanda D. Henderson, Anthony C. Arnold, Laura Bonelli, Heather E. Moss, Sylvia Elizabeth Villarreal Navarro, Tanyatuth Padungkiatsagul, Hadas Stiebel-Kalish, Itay Lotan, Adi Wilf-yarkoni, Helen Danesh-Meyer, Stefan Ivanov, Saif Huda, Mirasol Forcadela, David Hodge, Pascale Poullin, Julie Rode, Caroline Papeix, Samir Saheb, Marine Boudot De La Motte, Catherine Vignal, Yael Hacohen, Julie Pique, Elisabeth Maillart, Romain Deschamps, Bertrand Audoin, Romain Marignier
Summary: This study evaluated the effectiveness of plasma exchange (PLEX) for optic neuritis (ON). The results showed that most ON attacks improved with PLEX, and PLEX had better outcomes compared to similar severity cases.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2023)
Article
Ophthalmology
Lauren Hennein, Yingna Liu, Elizabeth A. Shuman, Jessica S. Kim, Heather E. Moss, Jeremy D. Keenan, Gerami D. Seitzman
Summary: A study found that male attendees are more likely to ask questions during virtual ophthalmology grand rounds compared to female attendees. Assessing the role of sex in participation is important for promoting equal participation in academic discourse.
JAMA OPHTHALMOLOGY
(2023)
Article
Cell Biology
Katia Corano Scheri, Yi-Wen Hsieh, Eunji Jeong, Amani A. Fawzi
Summary: The progression to fibrosis in retinopathy of prematurity and other ischemic retinopathies is a clinical and surgical challenge. In this study, a limited hyperoxia induced retinopathy model was used to evaluate the progression of fibrosis, angiogenesis, and inflammation in mice at different time points.
Article
Ophthalmology
Lauren Hennein, Yingna Liu, Elizabeth A. Shuman, Jessica S. Kim, Heather E. Moss, Jeremy D. Keenan, Gerami D. Seitzman
Summary: Sex disparities exist in academia, where female attendees ask fewer questions than male attendees. This study aimed to assess the role of sex in participation during virtual grand rounds at a major academic center. The findings suggest that male attendees are more likely to ask questions during virtual ophthalmology GR sessions.
JAMA OPHTHALMOLOGY
(2023)
Meeting Abstract
Clinical Neurology
Heather Moss, Lauren Wiener, Caitlin Rizy, Shrujal Baxi, Manan Kocher, Aracelis Torres, Michael Mbagwu
Meeting Abstract
Clinical Neurology
Delaney Oliver, Esther Kane, Shana Dodge, Roisheen Doherty, Gabe Goldfeder, Oana Popescu, Sonya Li, Aracelis Torres, Heather Moss