Article
Clinical Neurology
Federico Verde, Ivan Ferrari, Alessio Maranzano, Emilio Ciusani, Silvia Torre, Ilaria Milone, Eleonora Colombo, Alberto Doretti, Silvia Peverelli, Antonia Ratti, Luca Maderna, Barbara Poletti, Stefano Messina, Claudia Morelli, Vincenzo Silani, Nicola Ticozzi
Summary: This study analyzed the relationship between cerebrospinal fluid/serum albumin quotient (Q-Alb) and phenotype in a large cohort of amyotrophic lateral sclerosis (ALS) patients. It found that Q-Alb was not associated with age, but was independently associated with sex, with higher levels in male patients. Q-Alb was not associated with onset site or other phenotypic features, but had a weak positive correlation with an electromyography-based index of active limb denervation.
NEUROLOGICAL SCIENCES
(2023)
Article
Pharmacology & Pharmacy
J. Daniel Bireley, John A. Morren
Summary: This article provides an overview of current amyotrophic lateral sclerosis (ALS) treatments, including riluzole, edaravone, AMX0035, and tofersen. It also discusses the potential of CNM-Au8, an energy metabolism catalyst, as a disease-modifying treatment for ALS. While the phase 2/3 clinical trials of CNM-Au8 did not meet primary endpoints, exploratory endpoints suggest its potential in slowing clinical worsening, improving quality of life, and prolonging survival in ALS. Phase 3 clinical trials of CNM-Au8 are currently underway.
EXPERT OPINION ON INVESTIGATIONAL DRUGS
(2023)
Review
Cell Biology
Maximilian Vidovic, Lars Hendrik Mueschen, Svenja Brakemeier, Gerrit Machetanz, Marcel Naumann, Sergio Castro-Gomez
Summary: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by loss of upper and lower motor neurons, resulting in progressive weakness of voluntary muscles and eventual respiratory failure. Diagnosis is primarily based on clinical findings supported by electrophysiological and laboratory measurements, but research on disease-specific fluid biomarkers and advances in imaging techniques have improved diagnostic accuracy. Genetic testing allows for early identification of ALS-related gene mutations and access to clinical trials for disease-modifying therapies. Personalized survival prediction models provide detailed prognosis information. This review summarizes established diagnostic procedures and future directions in ALS diagnostics to improve the diagnostic pathway for this burdensome disease.
Article
Clinical Neurology
Daniel Baumgartner, Radim Mazanec, Jitka Hanzalova
Summary: This study measured the levels of NfL and p-NfH in cerebrospinal fluid (CSF) and p-NfH in serum to assess their diagnostic performance as markers of MND. The results showed that NfL and p-NfH in CSF were reliable diagnostic markers for MND, while p-NfH in serum had limited diagnostic ability.
JOURNAL OF NEUROLOGY
(2023)
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
Multidisciplinary Sciences
Radhika Khosla, Manjari Rain, Suresh Sharma, Akshay Anand
Summary: ALS is a degenerative disorder of motor neurons, and early diagnosis is crucial for predicting the disease and its progression. The study presents a predictive statistical model for ALS using plasma and CSF biomarkers, showing good validity, sensitivity, and specificity.
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)
Review
Cell Biology
Laura Tzeplaeff, Sibylle Wilfling, Maria Viktoria Requardt, Meret Herdick
Summary: Finding effective therapy for ALS is challenging, as the exact cause and pathological pathway are unknown. Current approved drugs only have moderate effects and no curative options are available. Recent breakthroughs in genetic research bring hope for improved treatment, but more efforts are needed.
Review
Biochemistry & Molecular Biology
Soju Seki, Yoshihiro Kitaoka, Sou Kawata, Akira Nishiura, Toshihiro Uchihashi, Shin-ichiro Hiraoka, Yusuke Yokota, Emiko Tanaka Isomura, Mikihiko Kogo, Susumu Tanaka
Summary: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the degeneration of motor neurons, with emerging evidence suggesting involvement of sensory neurons. Clinical research has shown sensory symptoms and abnormal nerve conduction in ALS patients, while preclinical research has identified genetic abnormalities in both sensory and motor neurons. This review highlights the potential of targeting sensory neuron abnormalities in ALS for new therapies.
Article
Multidisciplinary Sciences
Arvin Behzadi, Fani Pujol-Calderon, Anton E. Tjust, Anna Wuolikainen, Kina Hoglund, Karin Forsberg, Erik Portelius, Kaj Blennow, Henrik Zetterberg, Peter Munch Andersen
Summary: Elevated levels of CSF NFL, CSF pNFH, and plasma NFL are significantly associated with ALS, providing diagnostic value in differentiating ALS from other neurological diseases. Plasma NFL levels can help differentiate between clinical and genetic subgroups of ALS. Survival rate is negatively correlated with all three biomarkers.
SCIENTIFIC REPORTS
(2021)
Article
Medicine, Research & Experimental
Alexander Frohlich, Abigail L. Pfaff, Vivien J. Bubb, John P. Quinn, Sulev Koks
Summary: This study analyzed differential gene expression in amyotrophic lateral sclerosis (ALS) using cerebrospinal fluid (CSF) RNA-sequencing data. The affected genes were found to be enriched in several pathways associated with the disease. Additionally, the expression of previously identified potential biomarkers was significantly higher in ALS individuals, providing insight into biomarker development.
EXPERIMENTAL BIOLOGY AND MEDICINE
(2023)
Article
Medicine, General & Internal
Eleonora Volpato, Michele Vitacca, Luciana Ptacinsky, Agata Lax, Salvatore D'Ascenzo, Enrica Bertella, Mara Paneroni, Silvia Grilli, Paolo Banfi
Summary: In ALS patients, home-based adaptation to NIV is as effective as outpatient adaptation in terms of PaCO2, acceptance, and adherence, highlighting the need for further studies on the role of the environment in NIV adherence.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Neurosciences
Rangariroyashe H. Chipika, Grainne Mulkerrin, Aizuri Murad, Jasmin Lope, Orla Hardiman, Peter Bede
Summary: This prospective neuroimaging study systematically evaluated the differences in processing sensory information between amyotrophic lateral sclerosis (ALS) patients and healthy controls. The results showed widespread alterations in cerebral grey and white matter structures involved in sensory processing, including somatosensory, visual, and auditory regions. These findings suggest that ALS not only affects motor system degeneration and cognitive dysfunction, but also impairs sensory pathways, which is of clinical significance for ALS assessments.
JOURNAL OF INTEGRATIVE NEUROSCIENCE
(2022)
Article
Clinical Neurology
Peter Bede, Aizuri Murad, Jasmin Lope, Orla Hardiman, Kai Ming Chang
Summary: This study conducted a prospective research using an imaging protocol to identify subtypes of amyotrophic lateral sclerosis (ALS) based on preferential cerebral involvement. Cluster analysis revealed two radiological clusters with different patterns of brain regions involvement. The hierarchy of anatomical regions in decreasing importance was also identified.
JOURNAL OF NEUROLOGY
(2022)
Article
Geriatrics & Gerontology
Federico Verde, Ilaria Milone, Eleonora Colombo, Alessio Maranzano, Federica Solca, Silvia Torre, Alberto Doretti, Francesco Gentile, Arianna Manini, Ruggero Bonetti, Silvia Peverelli, Stefano Messina, Luca Maderna, Claudia Morelli, Barbara Poletti, Antonia Ratti, Vincenzo Silani, Nicola Ticozzi
Summary: This study investigated the relationship between serum levels of the neuroaxonal degeneration biomarker NFL and phenotype in ALS. The results showed that sNFL levels were increased in ALS patients and could distinguish them from neurologically healthy controls. sNFL levels were higher in phenotypes with both UMN and LMN signs, especially in those with UMN predominance. sNFL was also associated with disease progression rate, King's stages, and survival.
FRONTIERS IN AGING NEUROSCIENCE
(2023)
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
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
Clinical Neurology
Ozlem Yildiz, Johannes Schroth, Timothy Tree, Martin R. Turner, Pamela J. Shaw, Sian M. Henson, Andrea Malaspina
Summary: In this study, researchers found that aging exacerbates neuroinflammation and older age is associated with a worse prognosis in ALS. They also discovered activation of cell senescence pathways and increase of proinflammatory cytokines in ALS patients. The findings suggest that lymphocyte senescence and memory state may play a central role in the progression of ALS.
NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION
(2023)
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)
Article
Biochemical Research Methods
Zerin Alimajstorovic, Susan P. Mollan, Olivia Grech, James L. Mitchell, Andreas Yiangou, Mark Thaller, Hannah Lyons, Matilde Sassani, Senali Seneviratne, Thomas Hancox, Andris Jankevics, Lukas Najdekr, Warwick Dunn, Alexandra J. Sinclair
Summary: This study utilized metabolomic analysis to compare the cerebrospinal fluid and serum of patients with idiopathic intracranial hypertension (IIH) with control subjects. The results revealed differential metabolic pathways in IIH patients, which normalized after treatment. These pathways were associated with clinical measures and provide initial insights into the pathogenesis of IIH.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Spectroscopy
James J. P. Alix, Maria Plesia, Chloe N. Schooling, Alexander P. Dudgeon, Catherine A. Kendall, Visakan Kadirkamanathan, Christopher J. McDermott, Grainne S. Gorman, Robert W. Taylor, Richard J. Mead, Pamela J. Shaw, John C. Day
Summary: Raman spectroscopy shows promise as a biomarker for neuromuscular diseases. Challenges include sensitivity to instrument configurations, translation across tissues, and development of analytics for disease identification. Nonnegative matrix factorisation (NMF) was used to analyse Raman spectra from different clinical and preclinical settings, accurately identifying disease states. NMF decomposition enhances the potential of Raman spectroscopy for studying fatal neuromuscular diseases.
JOURNAL OF RAMAN SPECTROSCOPY
(2023)
Article
Medicine, Legal
Rossana Cecchi, Vittoria Masotti, Matilde Sassani, Alessandra Sannella, Giulia Agugiaro, Tomoya Ikeda, Davide Maria Pressanto, Emanuele Caroppo, Maria Laura Schirripa, Marianna Mazza, Toshikazu Kondo, Pietro De Lellis
Summary: This paper applies a proposed definition of femicide to a cohort of cases to characterize femicides and female homicides and evaluate if femicides can be considered as a distinct entity. Comparisons between female and male homicides reveal common and distinctive features, such as a higher prevalence of indoor homicides and asphyxiation in female homicides. The study suggests that femicide and female homicide can be regarded as separate victimological phenomena.
Review
Biotechnology & Applied Microbiology
Richard J. Mead, Ning Shan, H. Joseph Reiser, Fiona Marshall, Pamela J. Shaw
Summary: Amyotrophic lateral sclerosis (ALS) is a devastating disease with degeneration of motor neurons. Despite the challenges, ALS has seen progress in the development of disease-modifying therapies. Significant advancements have been made in ALS research and novel therapeutic approaches are being applied to address unmet medical needs. This review discusses how advanced knowledge and new approaches can lead to effective translation of therapies for ALS and potentially impact drug discovery for neurodegenerative disorders.
NATURE REVIEWS DRUG DISCOVERY
(2023)
Review
Clinical Neurology
Ilaria Giovannelli, Adrian Higginbottom, Janine Kirby, Mimoun Azzouz, Pamela J. Shaw
Summary: Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease characterized by the progressive loss of motor neurons. Recent advances in genetic therapy offer new opportunities for treating ALS, although there are still challenges to overcome.
NATURE REVIEWS NEUROLOGY
(2023)
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
Ophthalmology
Mark Thaller, Victoria Homer, Matilde Sassani, Susan P. Mollan, Alexandra J. Sinclair
Summary: This prospective longitudinal cohort study found that the prevalence of comorbid polycystic ovary syndrome (PCOS) in women with idiopathic intracranial hypertension (IIH) was 20%. Patients with comorbid PCOS in IIH had an increased risk of fertility problems and the need for medical help in becoming pregnant. However, comorbid PCOS did not significantly impact long-term vision or headache outcomes.
Editorial Material
Law
Rossana Cecchi, Matilde Sassani, Francesco Saverio Romolo, Alfredo Rovito, Massimo Montisci, Vittoria Masotti, Alessandra Sannella
Summary: On 16th June 2022, the first case of lawful 'medically assisted suicide' occurred in Italy, following years of debates on informed consent and end-of-life care prompted by medical jurisprudence. The authors examine the significant moments that led to this milestone and highlight the remaining challenges. The cases of DJ Fabo, Davide Trentin, Mario and Fabio Ridolfi are discussed to illustrate their impact on Italian jurisprudence.
MEDICINE SCIENCE AND THE LAW
(2023)
Article
Clinical Neurology
Thomas Payne, Matthew Appleby, Ellen Buckley, Linda M. A. van Gelder, Benjamin H. H. Mullish, Matilde Sassani, Mark J. J. Dunning, Dena Hernandez, Sonja W. W. Scholz, Alisdair McNeill, Vincenzo Libri, Sarah Moll, Julian R. R. Marchesi, Rosie Taylor, Li Su, Claudia Mazza, Thomas M. M. Jenkins, Thomas Foltynie, Oliver Bandmann
Summary: The study demonstrated that high-dose UDCA is safe and well tolerated in early PD patients. P-31-MRS results showed improved ATP hydrolysis in the midbrain of the UDCA treatment group, and sensor-based gait analysis indicated possible improvement in gait parameters. Larger trials are necessary to further evaluate the disease-modifying effect of UDCA in PD.
MOVEMENT DISORDERS
(2023)
Article
Cell Biology
Lydia M. Castelli, Ya-Hui Lin, Alvaro Sanchez-Martinez, Aytac Gul, Kamallia Mohd Imran, Adrian Higginbottom, Santosh Kumar Upadhyay, Nora M. Markus, Raquel Rua Martins, Johnathan Cooper-Knock, Claire Montmasson, Rebecca Cohen, Amy Walton, Claudia S. Bauer, Kurt J. De Vos, Richard J. Mead, Mimoun Azzouz, Cyril Dominguez, Laura Ferraiuolo, Pamela J. Shaw, Alexander J. Whitworth, Guillaume M. Hautbergue
Summary: Hexanucleotide repeat expansions in C9ORF72 are a common genetic cause of familial ALS and FTD. These expansions result in the translation of neurotoxic DPRs that contribute to neurodegeneration. A cell-penetrant peptide was found to block the export and translation of C9ORF72-repeat transcripts and toxic DPRs, leading to improved survival of ALS motor neurons and decreased DPR expression in animal models. Disrupting DPR production may be a potential strategy to ameliorate neurodegeneration in ALS/FTD.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Neurosciences
Brett N. Adey, Johnathan Cooper-Knock, Ahmad Al Khleifat, Isabella Fogh, Philip van Damme, Philippe Corcia, Philippe Couratier, Orla Hardiman, Russell McLaughlin, Marc Gotkine, Vivian Drory, Vincenzo Silani, Nicola Ticozzi, Jan H. Veldink, Leonard H. van den Berg, Mamede de Carvalho, Susana Pinto, Jesus S. Mora S. Pardina, Monica Povedano Panades, Peter M. Andersen, Markus Weber, Nazli A. Basak, Christopher E. Shaw, Pamela J. Shaw, Karen E. Morrison, John E. Landers, Jonathan D. Glass, Patrick Vourc'h, Richard J. B. Dobson, Gerome Breen, Ammar Al-Chalabi, Ashley R. Jones, Alfredo Iacoangeli
Summary: This study explores the relationship between CAV1/2 genes and ALS. The expression of CAV1 and CAV2 genes is found to be higher in ALS patients compared to controls, and carriers of CAV1/2 enhancer mutations show improved survival and slower progression of the disease.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)