Review
Pharmacology & Pharmacy
Javier Riancho, Lucia Paz-Fajardo, Adolfo Lopez de Munain
Summary: ALS, commonly known as Lou Gehrig's disease, is not only limited to motor neuron degeneration but also involves sensory systems. Studies have shown sensory fiber loss and hyperexcitability in the somatosensory cortex in ALS patients. Animal studies support the involvement of sensory-motor networks in the disease, indicating a need for more comprehensive research approaches.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Clinical Neurology
F. C. Garton, B. B. Trabjerg, N. R. Wray, E. Agerbo
Summary: The study revealed a linear relationship between ALS incidence and age, with individuals with prior cardiovascular disease diagnosis having a higher risk of developing ALS. Gender differences were also found to play a role in ALS risk, with men showing a slightly lower risk compared to women.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Review
Biochemistry & Molecular Biology
Delia Gagliardi, Nereo Bresolin, Giacomo Pietro Comi, Stefania Corti
Summary: Extracellular vesicles (EVs) serve as small reservoirs of molecules and play important roles in cell-to-cell communication, with potential implications in disease pathogenesis and therapy. They are not only being studied as diagnostic and prognostic biomarkers but also as valuable tools for understanding disease mechanisms and exploring therapeutic applications.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Review
Geriatrics & Gerontology
Valentina Gnoni, Stefano Zoccolella, Alessia Giugno, Daniele Urso, Ludovica Tamburrino, Marco Filardi, Giancarlo Logroscino
Summary: This review summarizes studies on sleep disorders in amyotrophic lateral sclerosis (ALS) published between 2000 and 2023, and examines the potential mechanisms by which hypothalamic dysfunctions contribute to ALS-related sleep disturbances. Gaining a deeper understanding of the relationship between hypothalamic dysfunction and sleep disturbances in ALS can enhance the management of ALS and alleviate the burden on patients and their families.
FRONTIERS IN AGING NEUROSCIENCE
(2023)
Review
Biotechnology & Applied Microbiology
Ravichandran Manjupriya, Kamalanathan Pouthika, Gunabalan Madhumitha, Selvaraj Mohana Roopan
Summary: This review summarizes the recent research progress in using nitrogen ring systems to treat ALS. It provides insights on effective synthetic techniques for nitrogen-based heterocyclic medications that can function as potent anti-inflammatory treatments and prevent the occurrence of ALS.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2022)
Review
Immunology
Zongzhi Jiang, Ziyi Wang, Xiaojing Wei, Xue-Fan Yu
Summary: This review article summarizes the role and application of inflammatory markers in amyotrophic lateral sclerosis (ALS). Inflammatory molecules and proteins play a key role in the pathogenesis of ALS and may serve as indicators for predicting patient survival and evaluating treatment response. Furthermore, inflammatory markers have the potential to be used as new therapeutic targets and strategies to expand the therapeutic interventions for ALS.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Clinical Neurology
Philippe Corcia, Pascal Lejeune, Patrick Vourc'h, Stephane Beltran, Anne-Sophie Piegay, Helene Blasco, Vincent Meininger
Summary: This study characterized the prototypical phenotype of patients with amyotrophic lateral sclerosis (ALS) associated with PFN1 mutations and identified clinical indications for testing mutations in this gene. The main clinical findings for familial ALS linked to PFN1 were identified as pedigrees with over five cases, an onset age around 50 years, onset in the lower limbs, and the absence of cognitive impairment. The similarities with other ALS mutations prompt a review of ALS classifications based on both phenotype and genotype.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Review
Pharmacology & Pharmacy
JingSi Jiang, Yan Wang, Min Deng
Summary: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder. Currently, there are only a few drugs that can extend the survival time of patients. However, there are many new experimental drugs being tested in clinical trials, and several of them have shown promising therapeutic effects.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Clinical Neurology
Rossella Spataro, Vincenzo La Bella
Summary: The study found that most ALS patients can retain full ability to choose between treatment options, but some patients may have reduced capacity. Age, education level, cognitive abilities, and depression may affect the outcomes of treatment consent capacity.
JOURNAL OF NEUROLOGY
(2021)
Review
Clinical Neurology
Thomas H. Julian, Sarah Boddy, Mahjabin Islam, Julian Kurz, Katherine J. Whittaker, Tobias Moll, Calum Harvey, Sai Zhang, Michael P. Snyder, Christopher McDermott, Johnathan Cooper-Knock, Pamela J. Shaw
Summary: Mendelian randomization studies on amyotrophic lateral sclerosis show a causal link between blood lipids and the disease risk, while factors like smoking and immune function require further investigation for confirmation. The use of high methodological standards and replication across different datasets are essential for reliable results in Mendelian randomization studies.
Article
Rehabilitation
Amina Ben Salah, Pierre-Francois Pradat, Marie Villain, Alexander Balcerac, Pascale Pradat-Diehl, Francois Salachas, Lucette Lacomblez, Eleonore Bayen
Summary: ALS patients may experience anosognosia, particularly in terms of cognitive-behavioral disorders and apathy symptoms. Caregivers often report more severe symptoms of patients compared to what the patients themselves recognize.
ANNALS OF PHYSICAL AND REHABILITATION MEDICINE
(2021)
Article
Clinical Neurology
Seok-Jin Choi, C. Hyung Keun Park, Yoon-Ho Hong, Jung-Joon Sung
Summary: This study aimed to investigate the association between ALS and psychiatric disorders. The results showed that psychiatric disorders were common in both fALS and sALS patients, with depressive disorders and anxiety and stress disorders being the most frequent. However, the study found no evidence that depression or anxiety increase the risk of developing ALS.
AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
(2022)
Article
Clinical Neurology
Paride Schito, Tommaso Russo, Teuta Domi, Alessandra Mandelli, Laura Pozzi, Ubaldo Del Carro, Paola Carrera, Federica Agosta, Angelo Quattrini, Roberto Furlan, Massimo Filippi, Nilo Riva
Summary: The study aims to determine the features at onset that can differentiate between primary lateral sclerosis (PLS) and amyotrophic lateral sclerosis (ALS), evaluate the diagnostic performance of a serum biomarker panel, and identify prognostic factors for patients with upper motor neuron syndrome.
Review
Medicine, General & Internal
Can Cui, Jiangwei Sun, Kyla A. McKay, Caroline Ingre, Fang Fang
Summary: This systematic review investigated the association between medication use and ALS risk, and found no strong evidence linking any medication use with the risk of ALS.
Article
Neurosciences
Shuangwu Liu, Yuying Zhao, Qingguo Ren, Dong Zhang, Kai Shao, Pengfei Lin, Ying Yuan, Tingjun Dai, Yongqing Zhang, Ling Li, Wei Li, Peiyan Shan, Xiangshui Meng, Qian Wang, Chuanzhu Yan
Summary: This study investigated amygdala abnormalities in ALS patients, revealing distinct patterns at different clinical disease stages and highlighting their impact on anxiety and cognitive dysfunction.
HUMAN BRAIN MAPPING
(2022)
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)
