Article
Clinical Neurology
Maria Ida Pateri, Silvy Pilotto, Giuseppe Borghero, Francesca Pili, Vincenzo Pierri, Tommaso Ercoli, Angelo Fabio Gigante, Antonella Muroni, Giovanni Defazio
Summary: While ALS incidence has increased in recent years, this study in Southern Sardinia found a non-significant increase in ALS prevalence from 2015 to 2019. However, a significant rise in prevalence was observed in tracheostomized ALS patients during this period, while non-tracheostomized patients showed no significant difference.
NEUROLOGICAL SCIENCES
(2023)
Article
Food Science & Technology
Salvatore D'Antona, Martina Caramenti, Danilo Porro, Isabella Castiglioni, Claudia Cava
Summary: Amyotrophic lateral sclerosis (ALS) is a fatal disease linked to motor neurons degeneration, with diet components like oxidative stress potentially influencing its onset. Some diets with antioxidant and anti-inflammatory properties may reduce the risk of ALS, but current data remains controversial.
Review
Clinical Neurology
Laura Chapman, Johnathan Cooper-Knock, Pamela J. Shaw
Summary: Chapman et al. reviewed published evidence on the link between strenuous physical activity and the development of ALS. The consensus supports physical activity as a risk factor for ALS, with genetic susceptibility also playing a role.
Article
Clinical Neurology
Giammarco Milella, Stefano Zoccolella, Alessia Giugno, Marco Filardi, Daniele Urso, Salvatore Nigro, Benedetta Tafuri, Ludovica Tamburrino, Valentina Gnoni, Giancarlo Logroscino
Summary: This study found that spinal-onset ALS can be categorized into three groups based on the extent of upper motor neuron (UMN) and lower motor neuron (LMN) involvement. UMN burden is associated with higher diagnostic certainty and broader disease spread, while LMN involvement is associated with more severe disease and shorter survival.
JOURNAL OF NEUROLOGY
(2023)
Review
Cell Biology
Giulia Guidotti, Chiara Scarlata, Liliana Brambilla, Daniela Rossi
Summary: The involvement of TNF alpha in ALS is controversial, with studies suggesting both protective and detrimental functions depending on the type of TNF alpha receptor activated. Understanding the impact of this cytokine on disease progression may lead to the development of effective therapies targeting the protective roles of TNF alpha and minimizing the detrimental effects.
Article
Clinical Neurology
Alejandra Camacho-Soto, Susan Searles Nielsen, Irene M. Faust, Robert C. Bucelli, Timothy M. Miller, Brad A. Racette
Summary: This study aimed to investigate the incidence and survival rates of amyotrophic lateral sclerosis (ALS) in Medicare beneficiaries aged 66 to 90. The findings suggest that older and marginalized ALS patients are less likely to be accurately diagnosed and included in epidemiological studies.
Review
Clinical Neurology
Georgiana Soares Leandro, Mario Emilio Teixeira Dourado Junior, Glauciane Costa Santana, Luan Samy Xavier Dantas
Summary: The main coping strategy used by ALS patients is seeking social support, while Confrontive coping and Distancing are less commonly mentioned. The coping strategies of ALS patients do not seem to focus on emotions or stress-triggering problems, and age and gender do not modify the chosen strategy.
JOURNAL OF NEUROLOGY
(2022)
Article
Clinical Neurology
Eleonora Colombo, Alberto Doretti, Francesco Scheveger, Alessio Maranzano, Giulia Pata, Delia Gagliardi, Megi Meneri, Stefano Messina, Federico Verde, Claudia Morelli, Stefania Corti, Luca Maderna, Vincenzo Silani, Nicola Ticozzi
Summary: This study aimed to analyze the correlation between electrophysiological parameters and clinical characteristics of ALS. The results showed a significant association between AD and CD scores and disease progression, survival, and functional disability in ALS patients.
JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Patrizia M. Maier, Deetje Iggena, Thomas Meyer, Carsten Finke, Christoph J. Ploner
Summary: This study found no evidence of hippocampal dysfunction in non-demented ALS patients, suggesting that the cognitive phenotype of ALS may relate to distinct disease subtypes rather than being a variable expression of the same underlying condition.
JOURNAL OF NEUROLOGY
(2023)
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
Radiology, Nuclear Medicine & Medical Imaging
Giorgio Conte, Valeria Elisa Contarino, Silvia Casale, Claudia Morelli, Sara Sbaraini, Elisa Scola, Francesca Trogu, Silvia Siggillino, Claudia Maria Cinnante, Luca Caschera, Francesco Maria Lo Russo, Fabio Maria Triulzi, Vincenzo Silani
Summary: The study aimed to investigate whether magnetic susceptibility varies according to ALS phenotypes based on UMN/LMN sign predominance. Results showed significant differences in susceptibility properties of the precentral cortex among different clinical ALS phenotypes. Combined MRI-histopathology investigations are needed to confirm the evidence of iron overload in UMN-ALS unlike in LMN-ALS.
EUROPEAN RADIOLOGY
(2021)
Article
Cell Biology
Chaohua Cong, Weiwei Liang, Chunting Zhang, Ying Wang, Yueqing Yang, Xudong Wang, Shuyu Wang, Di Huo, Hongyong Wang, Di Wang, Honglin Feng
Summary: In ALS models, the expression and activation of PAK4 significantly decreased as the disease progressed due to the negative regulation of miR-9-5p. Silencing PAK4 increased apoptosis of motor neurons by inhibiting CREB-mediated neuroprotection, while overexpression of PAK4 protected motor neurons from degeneration by activating CREB signaling.
CELL PROLIFERATION
(2021)
Review
Clinical Neurology
Christian Wilson R. Turalde, Kevin Michael C. Moalong, Adrian I. Espiritu, Mario B. Prado
Summary: This study aimed to evaluate the efficacy and safety of perampanel in ALS patients in terms of functional status improvement. After reviewing relevant studies, the results showed that perampanel did not have sufficient evidence to support its role in improving functional status in ALS patients. However, it was found to improve cortical motor hyperexcitability. Adverse events such as aggression, somnolence, anger, and dysarthria were associated with perampanel use among ALS patients. Further studies are needed to investigate the potential benefits of perampanel in ALS, considering factors such as disease stage, specific patient characteristics, and titration schedule.
NEUROLOGICAL SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Bradley Roberts, Frances Theunissen, Francis L. Mastaglia, P. Anthony Akkari, Loren L. Flynn
Summary: This review provides a comprehensive overview of the literature on the etiology and development of ALS, as well as its commonalities with synucleinopathy disorders. It discusses the involvement of alpha Syn in ALS and motor neuron disease pathology, along with current theories and strategies for therapeutics in ALS treatment, with a focus on small molecule RNA technologies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biology
Gavin McCluskey, Karen E. Morrison, Colette Donaghy, Frederique Rene, William Duddy, Stephanie Duguez
Summary: Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease with complex pathogenesis involving disruption of multiple pathways. Extracellular vesicles (EVs), nanoscopic membrane-bound particles, play a crucial role in intercellular communication, and their involvement in ALS pathogenesis is increasingly recognized.
Editorial Material
Clinical Neurology
Benjamin R. Wakerley, Mei Hong Tan, Martin R. Turner
Article
Clinical Neurology
Johnathan Cooper-Knock, Thomas H. Julian, Emily Feneberg, J. Robin Highley, Maurice Sidra, Martin R. Turner, Kevin Talbot, Olaf Ansorge, Scott P. Allen, Tobias Moll, Tatyana Shelkovnikova, Lydia Castelli, Guillaume M. Hautbergue, Christopher Hewitt, Janine Kirby, Stephen B. Wharton, Richard J. Mead, Pamela J. Shaw
Summary: We describe a multi-generational pedigree of amyotrophic lateral sclerosis (ALS) with an autosomal dominant, fully penetrant mutation in the TDP-43 gene. The hallmark pathology of ALS is the mislocalization of TDP-43 and the formation of insoluble TDP-43-positive neuronal cytoplasmic inclusions. While the lower motor neurons showed typical TDP-43 pathology, the motor cortex did not show classical TDP-43-positive inclusions. Despite reduced overall TDP-43 protein expression, the mutated allele was transcribed and translated in patient fibroblasts and motor cortex tissue. Furthermore, the motor cortex tissue carrying the mutation showed atypical TDP-43 protein species but not typical C-terminal fragments. Our findings suggest that the p.Y374X mutation is responsible for a monogenic, fully penetrant form of ALS and expands the molecular phenotypes associated with TDP-43 mutations and ALS.
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
Hugo M. De Oliveira, Arunachalam Soma, Mark R. Baker, Martin R. Turner, Kevin Talbot, Timothy L. Williams
Summary: There is considerable variation in the practice of genetic testing for patients with sporadic motor neurone disease/amyotrophic lateral sclerosis (MND/ALS) and asymptomatic at-risk relatives in specialized care centers in the UK. Many healthcare professionals feel uncomfortable discussing genetic testing with MND/ALS patients and believe that routine genetic testing is not necessary for all patients with apparently sporadic disease. There are concerns regarding testing asymptomatic at-risk individuals and the majority view is that clinical genetics services should play a role in supporting genetic testing in MND/ALS, especially in asymptomatic individuals at risk of carrying pathogenic variants.
AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
(2023)
Article
Medicine, General & Internal
Eleanor Wilson, Nicola Turner, Christina Faull, Jonathan Palmer, Martin R. Turner, Scott Davidson
Summary: The aim of this research is to provide new understandings of the experiences of people living with motor neuron disease (plwMND) using tracheostomy ventilation (TV), and those of family members and healthcare professionals (HCPs) involved in their care.
Article
Medicine, Research & Experimental
Anna J. Kordala, Jessica Stoodley, Nina Ahlskog, Muhammad Hanifi, Antonio Garcia Guerra, Amarjit Bhomra, Wooi Fang Lim, Lyndsay M. Murray, Kevin Talbot, Suzan M. Hammond, Matthew J. A. Wood, Carlo Rinaldi
Summary: Spinal muscular atrophy (SMA) is an important genetic cause of infant mortality. The discovery of PRMT inhibitor MS023 shows promising potential for treating SMA and improving the disease phenotype, especially when combined with nusinersen. Further clinical investigation of PRMT inhibition as a standalone or add-on therapy for SMA is warranted.
EMBO MOLECULAR MEDICINE
(2023)
Article
Clinical Neurology
Eleni Christoforidou, Fabio A. Simoes, David Gordon, Kevin Talbot, Majid Hafezparast
Summary: This study examined the intracellular motor neuron pathology of mice with a combination of defective dynein and a TDP-43 mutation. The results showed upregulation of p62 and aggregation of TDP-43, partially recapitulating the human disease. These findings provide new insights into the relationship between dynein and TDP-43 and could be useful for further research on the TDP-43 pathology in ALS.
AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
(2023)
Editorial Material
Clinical Neurology
Rita Sattler, Bryan J. Traynor, Janice Robertson, Ludo Van den Bosch, Sami J. Barmada, Clive N. Svendsen, Matthew D. Disney, Tania F. Gendron, Philip C. Wong, Martin R. Turner, Adam Boxer, Suma Babu, Michael Benatar, Michael Kurnellas, Jonathan D. Rohrer, Christopher J. Donnelly, Lynette M. Bustos, Kendall Van Keuren-Jensen, Penny A. Dacks, Marwan N. Sabbagh
Summary: The summit highlighted the role of the C9ORF72 gene in FTD and ALS, covering disease mechanisms, therapeutic strategies, and biomarkers. Collaborative efforts aimed to break down existing disease silos and proposed composite endpoints for evaluating treatments covering clinical symptoms.
NEUROLOGY AND THERAPY
(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)