Article
Clinical Neurology
C. Toh, A. Keslake, T. Payne, A. Onwuegbuzie, J. Harding, K. Baster, N. Hoggard, P. J. Shaw, I. D. Wilkinson, T. M. Jenkins
Summary: This study analyzed MRI data of the brain and cervical spinal cord to investigate pathophysiological hypotheses in vivo. A cranio-caudal step-change in MND patients was observed, which requires further investigation in larger cohorts.
JOURNAL OF NEUROLOGY
(2023)
Review
Neurosciences
Koy Chong Ng Kee Kwong, Pratap K. Harbham, Bhuvaneish T. Selvaraj, Jenna M. Gregory, Suvankar Pal, Giles E. Hardingham, Siddharthan Chandran, Arpan R. Mehta
Summary: This review summarizes the 40-year history of CSF toxicity studies in ALS and discusses various proposed mechanisms such as glutamate excitotoxicity, proteotoxicity, and oxidative stress. The potential implications of a toxic CSF circulatory system in the pathophysiology of ALS and its significance in current ALS research are also considered.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Article
Clinical Neurology
Danielle Leighton, Morad Ansari, Judith Newton, David Parry, Elaine Cleary, Shuna Colville, Laura Stephenson, Juan Larraz, Micheala Johnson, Emily Beswick, Michael Wong, Jenna Gregory, Javier Carod Artal, Richard Davenport, Callum Duncan, Ian Morrison, Colin Smith, Robert Swingler, Ian Deary, Mary Porteous, Timothy Aitman, Siddharthan Chandran, George Gorrie, Suvankar Pal, Carolyn Lothian Birth Cohorts Grp, CARE-MND Consortium
Summary: This study investigated the phenotypes and genotypes of a cohort of long-surviving individuals with motor neuron disease (MND). The findings suggest that long survivors are characterized by younger age at onset, increased prevalence of primary lateral sclerosis (PLS), and longer diagnostic delay. Genetic analysis revealed potentially pathogenic variants in several MND-associated genes.
JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Sri Raghav Sista, Brian Crum, Albert Aboseif, Michelle F. Devine, Anastasia Zekeridou, M. Bakri Hammami, Mohammed M. Rezk, Andre Truffert, Patrice H. Lalive, Amy Kunchok, Andrew McKeon, Divyanshu Dubey
Summary: The association between IgLON5 autoimmunity and neurological manifestations, including motor neuron disease-like phenotype, is expanding. This study describes four cases of IgLON5 autoimmunity with motor neuron involvement and evaluates the IgLON5-IgG seropositivity in 109 amyotrophic lateral sclerosis cases. The presence of specific symptoms in patients with motor neuron disease-like phenotype should prompt evaluation for IgLON5-IgG autoantibodies. Immunomodulatory treatment for this autoimmune disease may lead to significant neurological improvement in a minority of cases.
JOURNAL OF NEUROLOGY
(2022)
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
Clinical Neurology
Justin Kwan, Mithila Vullaganti
Summary: Amyotrophic lateral sclerosis (ALS) is a common motor neuron disorder in adults, and it is important to differentiate it from similar diseases for accurate diagnosis.
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)
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
Radiology, Nuclear Medicine & Medical Imaging
Conte Giorgio, Sbaraini Sara, Morelli Claudia, Casale Silvia, Caschera Luca, Contarino Valeria Elisa, Scola Elisa, Cinnante Claudia, Trogu Francesca, Triulzi Fabio, Silani Vincenzo
Summary: The study aims to differentiate ALS and its subtypes from ALS mimics and healthy controls based on the assessment of iron-related hypointensity of the primary motor cortex in SWI. The Motor Cortex Susceptibility (MCS) score was significantly higher in the ALS group compared to healthy controls and ALS-mimicking disorder groups, with potential diagnostic utility.
EUROPEAN RADIOLOGY
(2021)
Article
Medicine, General & Internal
Helena Chaytow, Emily Carroll, David Gordon, Yu-Ting Huang, Dinja van der Hoorn, Hannah Louise Smith, Thomas Becker, Catherina Gwynne Becker, Kiterie Maud Edwige Faller, Kevin Talbot, Thomas Henry Gillingwater
Summary: The study demonstrates that modulating the activity of the glycolysis enzyme PGK1 can improve motor neuron function in models of amyotrophic lateral sclerosis (ALS). Treatment with terazosin, which increases PGK1 activity, extends survival, improves motor phenotypes, and protects against oxidative stress-induced cell death. This research provides a new potential approach for ALS therapy.
Article
Clinical Neurology
Alberto Raggi, Lorenzo Monasta, Ettore Beghi, Valeria Caso, Giulio Castelpietra, Stefania Mondello, Giorgia Giussani, Giancarlo Logroscino, Francesca Giulia Magnani, Marco Piccininni, Elisabetta Pupillo, Stefano Ricci, Luca Ronfani, Paola Santalucia, Davide Sattin, Silvia Schiavolin, Claudia Toppo, Eugenio Traini, Jaimie Steinmetz, Emma Nichols, Rui Ma, Theo Vos, Valery Feigin, Matilde Leonardi
Summary: The study shows that the incidence and prevalence of neurological conditions in Italy are increasing, mainly due to population aging and growth. Years lived with disability associated with neurological conditions have significantly increased, calling for actions to improve the situation.
JOURNAL OF NEUROLOGY
(2022)
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
Emily Beswick, Micheala Johnson, Judith Newton, Rachel Dakin, Amy Stenson, Sharon Abrahams, Alan Carson, Siddharthan Chandran, Suvankar Pal
Summary: This study investigates the factors affecting recruitment and retention in Motor Neuron Disease (MND) research. It found that older individuals with MND are less likely to participate in trials, while MND patients overall are highly motivated to engage in research.
JOURNAL OF NEUROLOGY
(2023)
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)
Review
Biochemistry & Molecular Biology
Angelika Krol-Grzymala, Edyta Sienkiewicz-Szlapka, Ewa Fiedorowicz, Dominika Rozmus, Anna Cieslinska, Andrzej Grzybowski
Summary: This review investigates and analyzes the biomarkers for AD, PD, and MS in tears. Through analyzing the recent original studies, the biomarkers present in tears that can be used for the diagnosis and management of these diseases are shown.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Clinical Neurology
Benjamin R. Wakerley, Mei Hong Tan, Martin R. Turner
Article
Clinical Neurology
Alexander G. Thompson, Kevin Talbot, Martin R. Turner
Summary: The study examined the relationship between metabolic parameters and the risk of ALS, revealing that HDL and apoA1 levels are associated with a reduced risk, while total cholesterol:HDL ratio is linked to an increased risk. Models incorporating multiple metabolic markers showed that high levels of LDL or apoB are associated with an increased risk, while higher levels of HDL or apoA are associated with a lower risk. Additionally, coronary artery disease, cerebrovascular disease, and increasing age were also found to be associated with an increased risk of ALS.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Review
Biochemical Research Methods
Alexander G. Thompson, Patrick Oeckl, Emily Feneberg, Robert Bowser, Markus Otto, Roman Fischer, Benedikt Kessler, Martin R. Turner
Summary: Proteomic analysis has played a significant role in studying ALS, helping to define common pathological changes and shifting focus towards RNA biology. It has also contributed to disease mechanism delineation and biomarker development, advancing the goal of objective disease activity measurements for therapeutic trials. Further developments in sensitivity and quantification are expected, with potential application in prevention strategies during the presymptomatic phase of human disease.
EXPERT REVIEW OF PROTEOMICS
(2021)
Review
Clinical Neurology
Marie Dreger, Robert Steinbach, Markus Otto, Martin R. Turner, Julian Grosskreutz
Summary: ALS is a progressive neurodegenerative disease with limited treatment options. Reliable biomarkers in the cerebrospinal fluid are crucial for disease classification and clinical trial design. While some molecules in the CSF have shown potential as biomarkers, further large-scale studies and validation are needed to advance precision medicine in ALS management.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Editorial Material
Clinical Neurology
Martin R. Turner
PRACTICAL NEUROLOGY
(2022)
Editorial Material
Clinical Neurology
Costa Savva, Martin R. Turner
PRACTICAL NEUROLOGY
(2022)
Review
Clinical Neurology
Thanuja Dharmadasa, Jakub Scaber, Evan Edmond, Rachael Marsden, Alexander Thompson, Kevin Talbot, Martin R. Turner
Summary: A minority of cases of amyotrophic lateral sclerosis (ALS) are caused by genetic variants, making genetic testing important for diagnosis and treatment. However, indiscriminate use of genetic screening can lead to potential harm. Common hereditary cause of ALS, C9ORF72, may also be associated with dementia. All neurologists should have a basic understanding of genetic testing's role in ALS.
PRACTICAL NEUROLOGY
(2022)
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)
Article
Medicine, General & Internal
Greig Joilin, Elizabeth Gray, Alexander G. Thompson, Kevin Talbot, P. Nigel Leigh, Sarah F. Newbury, Martin R. Turner, Majid Hafezparast
Summary: In this study, we investigated the expression of non-coding RNA transcripts in the cerebrospinal fluid of ALS patients compared to healthy controls. RNA-seq identified dysregulated non-coding RNA transcripts, but these were not validated with RT-qPCR. We conclude that cerebrospinal fluid is not a suitable source of diagnostic biomarkers.
ANNALS OF MEDICINE
(2022)
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
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.
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)
