Article
Clinical Neurology
Domenica Zaino, Valeria Serchi, Fabio Giannini, Barbara Pucci, Giacomo Veneri, Elena Pretegiani, Francesca Rosini, Lucia Monti, Alessandra Rufa
Summary: This study compared eye movements and visual search behaviors between spinal ALS and bulbar ALS patients, revealing distinct features. The findings suggest early involvement of the parieto-collicular-cerebellar network in spinal ALS and the fronto-brainstem circuit in bulbar ALS.
Article
Clinical Neurology
Maike F. Dohrn, Danique Beijer, Museer A. Lone, Elif Bayraktar, Piraye Oflazer, Rotem Orbach, Sandra Donkervoort, A. Reghan Foley, Aubrey Rose, Michael Lyons, Raymond J. Louie, Kenneth Gable, Teresa Dunn, Sitong Chen, Matt C. Danzi, Matthis Synofzik, Carsten G. Boennemann, A. Nazli Basak, Thorsten Hornemann, Stephan Zuchner
Summary: This study identified gain-of-function mutations in SPTLC2 in juvenile ALS patients, leading to dysregulated sphingolipid synthesis and a key role in the pathogenesis of Mendelian periodic paralysis. This finding may open new therapeutic avenues for motor neuron diseases.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Article
Clinical Neurology
Mariarita Galbiati, Marco Meroni, Marina Boido, Matilde Cescon, Paola Rusmini, Valeria Crippa, Riccardo Cristofani, Margherita Piccolella, Veronica Ferrari, Barbara Tedesco, Elena Casarotto, Marta Chierichetti, Marta Cozzi, Francesco Mina, Maria Elena Cicardi, Silvia Pedretti, Nico Mitro, Anna Caretto, Patrizia Rise, Angelo Sala, Andrew P. Lieberman, Paolo Bonaldo, Maria Pennuto, Alessandro Vercelli, Angelo Poletti
Summary: Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease characterized by motor neuron degeneration, muscle weakness, and an expansion of the CAG triplet repeat in the androgen receptor (AR) gene. In this study, the use of the antiandrogen bicalutamide and the natural disaccharide trehalose showed promising results in ameliorating SBMA pathology in a mouse model. These compounds reduced ARpolyQ toxicity, prevented autophagic flux blockage, and improved muscle morphology and function, suggesting their potential for future clinical trials in SBMA patients.
Article
Genetics & Heredity
Tanya Lehky, Christopher Grunseich
Summary: Juvenile amyotrophic lateral sclerosis (JALS) is a rare group of motor neuron disorders with gene association in 40% of cases, defined by onset before age 25. The most common gene mutations associated with JALS are FUS, SETX, and ALS2, with familial cases mostly inherited in an autosomal recessive pattern.
Article
Clinical Neurology
Marlene Tahedl, Ee Ling Tan, Rangariroyashe H. Chipika, Jennifer C. Hengeveld, Alice Vajda, Mark A. Doherty, Russell L. McLaughlin, We Fong Siah, Orla Hardiman, Peter Bede
Summary: This study longitudinally evaluated a large panel of imaging metrics in ALS patients, revealing progressive disconnection between the motor cortex and the brainstem. The study also confirmed the potential of bulbar imaging measures to discriminate between patients and controls. C9orf72 carriers exhibited lower brainstem volumes, lower cortico-medullary structural connectivity, and faster cortical thinning, while sporadic patients without bulbar symptoms already showed significant brainstem and cortico-medullary connectivity alterations.
JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Dae-Won Gwak, Seung-Hwan Jung, Yu-Sun Min, Jin-Sung Park, Hee-Jin Cho, Donghwi Park, Min Woo Hong, Min-Gu Kang
Summary: The study revealed correlations between tongue pressure and disease duration, swallowing dysfunction, and functional assessment in SBMA patients. Tongue pressure assessment is a useful tool for evaluating swallowing function and can serve as a potential biomarker for physical performance in SBMA.
FRONTIERS IN NEUROLOGY
(2021)
Article
Dentistry, Oral Surgery & Medicine
Deike Adamske, Adrienne Heyduck, Matthias Weidenmueller, Bettina Goericke, Tobias Frank, Arno Olthoff
Summary: The study aimed to evaluate bulbar motor dysfunction in ALS patients and found significantly lower maximal suction pressures in the patient group, with a significant correlation between reduced pressures and the degree of dysphagia. Manometric measurements in the oral cavity could serve as a simple tool for early detection and monitoring of dysphagia in ALS patients. Further large-scale studies are needed to confirm these findings.
JOURNAL OF ORAL REHABILITATION
(2021)
Article
Neurosciences
Elana Molotsky, Yuhong Liu, Andrew P. Lieberman, Diane E. Merry
Summary: This study examines the relationship between neuromuscular junction (NMJ) pathology and vulnerability of fast-twitch motor units in spinal and bulbar muscular atrophy (SBMA) mouse models. The research reveals significantly increased NMJ and myofiber pathology in fast-twitch motor units, along with metabolic dysregulation and myofiber atrophy.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Stefano Zoccolella, Alessia Giugno, Giammarco Milella, Marco Filardi, Alessandro Introna, Angela Fraddosio, Eustachio D'Errico, Valentina Gnoni, Ludovica Tamburrino, Daniele Urso, Francesca Caputo, Salvatore Misceo, Giancarlo Logroscino
Summary: This study proposed a new scoring scale to assess the bulbar lower motor neurons (LMN) involvement in amyotrophic lateral sclerosis (ALS) and evaluated its prognostic value. The results showed that this scale had good reliability in assessing ALS and could provide unique information in phenotyping and predicting survival.
Article
Biochemistry & Molecular Biology
Cecilia Simonini, Elisabetta Zucchi, Roberta Bedin, Ilaria Martinelli, Giulia Gianferrari, Nicola Fini, Gianni Soraru, Rocco Liguori, Veria Vacchiano, Jessica Mandrioli
Summary: The study found that CSF pNfH is significantly higher in classic and UMNp-ALS patients, and can differentiate them from UMN diseases with a better prognosis such as PLS and hSP. CSF pNfH independently predicted survival in UMN patients and classic/bulbar ALS, while in UMNp-ALS patients, the progression rate and presence of multifocal fasciculations were independent prognostic factors.
Article
Clinical Neurology
Xia Feng, Xiu-Tang Cheng, Pengli Zheng, Yan Li, Jill Hakim, Shirley Q. Zhang, Stacie M. Anderson, Kaari Linask, Ryan Prestil, Jizhong Zou, Zu-Hang Sheng, Craig Blackstone
Summary: This study reveals the mechanisms of mitochondrial dysfunction in spinal bulbar muscular atrophy (SBMA) and its association with aberrant interaction between ligand-free mutant AR and F-ATP synthase.
Article
Clinical Neurology
Laura J. Ball, Jenenne A. Geske, Elizabeth Burton, Gary L. Pattee
Summary: This study developed and preliminarily validated the Clinical Bulbar Assessment Scale (CBAS) as a comprehensive and reliable scale for assessing bulbar function in amyotrophic lateral sclerosis (ALS) patients.
Article
Genetics & Heredity
Tomoki Hirunagi, Kentaro Sahashi, Katherine G. Meilleur, Masahisa Katsuno
Summary: Recent advances in nucleic acid therapeutics have shown the potential to treat hereditary neurological disorders by targeting causative genes. This review focuses on the use of nucleic acid-based approaches in the treatment of spinal and bulbar muscular atrophy (SBMA) and related disorders, highlighting the potential therapeutic targets and discussing current limitations and future perspectives.
Review
Biochemistry & Molecular Biology
Jing Zhao, Claire H. Stevens, Andrew W. Boyd, Lezanne Ooi, Perry F. Bartlett
Summary: Activation of EphA4 is involved in the pathogenesis of MND, and inhibiting EphA4 can improve functional outcomes. This review presents evidence that EphA4 signaling directly causes cell death in motor neurons, and discusses three likely mechanisms underlying this effect.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Clinical Neurology
Wei Zhang, Jing Ma, Jiaying Shi, Shan Huang, Rongjuan Zhao, Xiaomin Pang, Juan Wang, Junhong Guo, Xueli Chang
Summary: The GGC repeat expansion in the 5' untranslated region of NOTCH2NLC gene is associated with a new phenotype of hereditary lower motor neuron syndrome. NOTCH2NLC genotyping should be performed to aid in the diagnosis of hereditary lower motor neuron syndromes.
JOURNAL OF NEUROLOGY
(2022)
Editorial Material
Clinical Neurology
Benjamin R. Wakerley, Mei Hong Tan, Martin R. Turner
Article
Clinical Neurology
Lucy S. Musson, Alexis Collins, Sarah Opie-Martin, Andrea Bredin, Esther V. Hobson, Emily Barkhouse, Mark C. Coulson, Theocharis Stavroulakis, Rebecca L. Gould, Ammar Al-Chalabi, Christopher J. McDermott
Summary: This study explores the impact of the Covid-19 pandemic on the care of amyotrophic lateral sclerosis (ALS) in the UK. The research reveals that the pandemic has led to sub-optimal care for patients, with longer waiting times, cancellation of face-to-face appointments, and the use of virtual consultations. While virtual consultations have benefits, concerns have been raised about incomplete assessments and disrupted testing and interventions. The study highlights the changes in ALS care and the concerns of patients and healthcare professionals, but the long-term implications remain unclear.
AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
(2023)
Article
Clinical Neurology
Carolyn A. Young, John Ealing, Christopher J. McDermott, Tim L. Williams, Ammar Al-Chalabi, Tahir Majeed, Kevin Talbot, Timothy Harrower, Christina Faull, Andrea Malaspina, Joe Annadale, Roger J. Mills, Alan Tennant
Summary: The aim of this study was to investigate whether the WHODAS 2.0 can provide interval level measurement of disability in ALS, allowing parametric analyses. The results showed that the WHODAS 2.0 can be used as a brief patient reported outcome measure to assess disability in ALS and can be used for surveillance of at risk populations.
AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
(2023)
Article
Clinical Neurology
Rubika Balendra, Ashley R. Jones, Ahmad Al Khleifat, Theresa Chiwera, Paul Wicks, Carolyn A. Young, Pamela J. Shaw, Martin R. Turner, P. Nigel Leigh, Ammar Al-Chalabi
Summary: ALS is a clinically heterogeneous disease and the King's clinical staging system has been proposed to aid in patient care, research, trial design and health economic analyses. This study validates the King's clinical staging system in four patient groups located in different regions and countries, demonstrating consistent results.
AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
(2023)
Review
Clinical Neurology
Michael Benatar, Joanne Wuu, Martin R. Turner
Summary: Interest in ALS biomarkers has increased significantly in the past 25 years, with the hope of using them to develop effective therapies. Neurofilament light chain (NfL) has emerged as a potential biomarker for ALS therapy development. The study discusses the evidence supporting the use of NfL in different clinical contexts, concluding that it can serve as a risk biomarker, a prognostic biomarker, and a pharmacodynamic biomarker.
Article
Clinical Neurology
C. A. Young, J. Ealing, C. J. McDermott, T. L. Williams, A. Al-Chalabi, T. Majeed, K. Talbot, T. Harrower, C. Faull, A. Malaspina, J. Annadale, R. J. Mills, A. Tennant
Summary: This study reveals that the prevalence of depression in ALS patients is close to a quarter, with most patients belonging to a single trajectory group. Estimates based on screening for current depressive symptoms underestimate the actual prevalence of depression.
AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
(2023)
Article
Clinical Neurology
Michael Benatar, Stephen A. Goutman, Kim A. Staats, Eva L. Feldman, Marc Weisskopf, Evelyn Talbott, Kuldip D. Dave, Neil M. Thakur, Ammar Al-Chalabi
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Letter
Clinical Neurology
Michael Benatar, Ammar Al-Chalabi, Anita Crawley, Joanne Wuu
Article
Clinical Neurology
Jeremy M. Shefner, Ammar Al-Chalabi, Jinsy A. Andrews, Adriano Chio, Mamede De Carvalho, Bettina M. Cockroft, Philippe Corcia, Philippe Couratier, Merit E. Cudkowicz, Angela Genge, Orla Hardiman, Terry Heiman-Patterson, Robert D. Henderson, Caroline Ingre, Carlayne E. Jackson, Wendy Johnston, Noah Lechtzin, Albert Ludolph, Nicholas J. Maragakis, Timothy M. Miller, Jesus S. Mora Pardina, Susanne Petri, Zachary Simmons, Leonard H. Van Den Berg, Lorne Zinman, Stuart Kupfer, Fady I. Malik, Lisa Meng, Tyrell J. Simkins, Jenny Wei, Andrew A. Wolff, Stacy A. Rudnicki
Summary: The objective of this study is to determine the target population and optimize the study design for the phase 3 clinical trial of reldesemtiv in ALS participants. The phase 2 study, FORTITUDE-ALS, showed that reldesemtiv had a significant effect on participants with intermediate and fast disease progression, leading to the implementation of specific eligibility criteria and design features in the phase 3 trial, COURAGE-ALS, to increase sensitivity in detecting treatment effects and reduce burden on participants and study sites.
AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
(2023)
Review
Clinical Neurology
Ali Shojaie, Silvia Rota, Ahmad Al Khleifat, K. Ray Chaudhuri, Ammar Al-Chalabi
Summary: Amyotrophic lateral sclerosis and Parkinson's disease, both neurodegenerative diseases affecting the motor system, are now known to also impact non-motor pathways. Non-motor symptoms play a significant role in determining the quality of life in Parkinson's disease, and there is growing interest in understanding the extent and role of these symptoms in amyotrophic lateral sclerosis. Hence, we conducted a review to summarize the current knowledge of non-motor symptoms in amyotrophic lateral sclerosis based on insights from Parkinson's disease.
AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
(2023)
Article
Clinical Neurology
Jeremy M. Shefner, Bill Jacobsen, Stuart Kupfer, Fady I. Malik, Lisa Meng, Jenny Wei, Andrew A. Wolff, Stacy A. Rudnicki
Summary: In an ALS clinical trial, the relationship between measurements of strength, function, and quality of life was assessed. The results showed a strong correlation between muscle strength quantified by dynamometry and functional capacity, indicating a direct relationship between muscle strength and specific functions important to ALS patients.
AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
(2023)
Article
Clinical Neurology
Ali Shojaie, Ahmad Al Khleifat, Sarah Opie-Martin, Payam Sarraf, Ammar Al-Chalabi
Summary: This study aimed to examine the nature and extent of non-motor symptoms in ALS. Through an online questionnaire and sharing on social media platforms, a total of 1018 responses were received, including 506 people with ALS and 421 unaffected individuals. The study found that people with ALS were more likely to report autonomic symptoms, pain, and psychiatric symptoms, which significantly impacted their quality of life. Therefore, the identification and management of non-motor symptoms are crucial in the clinical care of ALS patients.
AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
(2023)
Article
Clinical Neurology
Alexander G. Thompson, Rachael Marsden, Kevin Talbot, Martin R. Turner
Summary: Using routine health screening blood test data, this study found distinct pre-symptomatic biphasic blood cholesterol trajectories in individuals who later developed amyotrophic lateral sclerosis. The findings suggest that metabolic alterations may occur prior to the onset of motor symptoms in this disease. These findings provide further evidence for the importance of monitoring blood cholesterol levels for early detection and potential preventative therapy in amyotrophic lateral sclerosis.
BRAIN COMMUNICATIONS
(2023)
Article
Clinical Neurology
Jennifer C. Davies, Thanuja Dharmadasa, Alexander G. Thompson, Evan C. Edmond, Katie Yoganathan, Jiali Gao, Kevin Talbot, Martin R. Turner
Summary: A reliable biomarker for diagnosing amyotrophic lateral sclerosis (ALS) across different clinical conditions is necessary. Neurofilament light chain levels are correlated with the progression of disability in ALS patients. Previous studies have only compared neurofilament light chain levels in ALS patients with healthy individuals or controls with diagnoses distinct from ALS. In this study, neurofilament light chain levels were measured in ALS patients referred to a specialized clinic, and it was found that neurofilament light chain levels can confirm ALS diagnosis but have limited ability to exclude alternative diagnoses. The current importance of neurofilament light chain is its potential use in stratifying ALS patients by disease activity and as a biomarker in therapeutic trials.
BRAIN COMMUNICATIONS
(2023)
