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)
Article
Clinical Neurology
Philippe Corcia, Christian Lunetta, Philippe Couratier, Patrick Vourc'h, Marta Gromicho, Claude Desnuelle, Marie-Helene Soriani, Susana Pinto, Mamede de Carvalho
Summary: The study found that PLS and ALS cases occurred in nine families, generally among first-degree relatives. Patients with both diseases exhibited typical disease characteristics, and genetic studies revealed mutations in specific genes in some patients. These results strongly support a phenotypic continuum between PLS and ALS.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Article
Geriatrics & Gerontology
Sandrine Chan Moi Fat, Emily P. McCann, Kelly L. Williams, Lyndal Henden, Natalie A. Twine, Denis C. Bauer, Roger Pamphlett, Matthew C. Kiernan, Dominic B. Rowe, Garth A. Nicholson, Jennifer A. Fifita, Ian P. Blair
Summary: Mutations in GLT8D1 and ARPP21 are not a common cause of ALS in Australian familial and sporadic cohorts, as no novel mutations were identified in either gene.
NEUROBIOLOGY OF AGING
(2021)
Article
Medicine, General & Internal
A. Panio, C. Cava, S. D'Antona, G. Bertoli, D. Porro
Summary: Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by the neurodegeneration of motoneurons. This study aims to identify specific blood miRNAs with diagnostic abilities for sporadic ALS (sALS) through a meta-analysis of the literature and bioinformatics approaches. A panel of 10 miRNAs was identified, and the expression levels of miR-193b/miR-4745-5p could potentially be used for the clinical diagnosis of sALS.
FRONTIERS IN MEDICINE
(2022)
Article
Clinical Neurology
Melina Pazian Martins, Carelis Gonzalez-Salazar, Fabricio Diniz de Lima, Tauana Bernardes Leoni, Alberto R. M. Martinez, Joao Pedro Nunes Goncalves, Anamarli Nucci, Marcondes Cavalcante Franca Jr
Summary: This study characterized and compared the autonomic function of patients with sporadic ALS and familial ALS type 8. The results showed that both types of ALS patients had dysautonomia involving both sympathetic and parasympathetic divisions, but the symptoms were different between the two groups.
CLINICAL NEUROPHYSIOLOGY
(2023)
Article
Genetics & Heredity
Robert Logan, Juleah Dubel-Haag, Nicolas Schcolnicov, Sean J. Miller
Summary: Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disorder with multiple genetic factors. Genetic testing can be critical in assessing a patient's risk for ALS, but most cases are sporadic and have no known associated genetic signatures. Our analysis of whole genome sequencing data has identified novel mutations in protein-coding genes associated with sporadic ALS, and these mutations can be used as genetic biomarkers for early ALS diagnosis.
FRONTIERS IN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Jose R. Monteiro Neto, Gabriela D. Ribeiro, Rayne S. S. Magalhaes, Cristian Follmer, Tiago F. Outeiro, Elis C. A. Eleutherio
Summary: This study found a relationship between the formation of methylglyoxal (MGO) and the degeneration of motor neurons in Amyotrophic Lateral Sclerosis (ALS). The accumulation of MGO led to the aggregation of human SOD1WT (hSOD1WT), decreased activity, and reduced cell viability. Additionally, MGO treatment increased the presence of hSOD1WT in stress granules. These findings suggest that glycation may play a significant role in the pathologies of hSOD1WT and TDP-43 in sporadic ALS.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Article
Clinical Neurology
Hitoshi Aizawa, Haruhisa Kato, Koji Oba, Takuya Kawahara, Yoshihiko Okubo, Tomoko Saito, Makiko Naito, Makoto Urushitani, Akira Tamaoka, Kiyotaka Nakamagoe, Kazuhiro Ishii, Takashi Kanda, Masahisa Katsuno, Naoki Atsuta, Yasushi Maeda, Makiko Nagai, Kazutoshi Nishiyama, Hiroyuki Ishiura, Tatsushi Toda, Akihiro Kawata, Koji Abe, Ichiro Yabe, Ikuko Takahashi-Iwata, Hidenao Sasaki, Hitoshi Warita, Masashi Aoki, Gen Sobue, Hidehiro Mizusawa, Yutaka Matsuyama, Tomohiro Haga, Shin Kwak
Summary: The study evaluated the efficacy and safety of Perampanel in patients with sporadic amyotrophic lateral sclerosis (SALS). It found that Perampanel was associated with a significant decline in ALSFRS-R score, especially in the 8 mg group. Serious adverse events were more frequent in the Perampanel 8 mg group compared to the placebo group.
JOURNAL OF NEUROLOGY
(2022)
Article
Neurosciences
Rehab F. Abdelhamid, Kotaro Ogawa, Goichi Beck, Kensuke Ikenaka, Eriko Takeuchi, Yoshiaki Yasumizu, Jyunki Jinno, Yasuyoshi Kimura, Kousuke Baba, Yoshitaka Nagai, Yukinori Okada, Yuko Saito, Shigeo Murayama, Hideki Mochizuki, Seiichi Nagano
Summary: The mislocalization and aggregation of TDP-43 in ALS cases may be related to the dysregulation of piRNA biogenesis. The dysregulation of PIWIL1 and PIWIL4, two PIWI homologs, could be key factors in the pathogenesis of ALS. These findings suggest that piRNAs and PIWI proteins may serve as potential diagnostic biomarkers and therapeutic targets for ALS.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Clinical Neurology
Victoria Baskerville, Sampath Rapuri, Emma Mehlhop, Alyssa N. Coyne
Summary: Researchers have found that defects in nuclear-cytoplasmic cellular compartmentalization and specific nuclear membrane proteins trigger the nuclear accumulation of CHMP7 in patients with sporadic amyotrophic lateral sclerosis (sALS), leading to a cascade of nuclear pore complex injury implicated in ALS pathogenesis.
Article
Clinical Neurology
Haruhisa Kato, Makiko Naito, Tomoko Saito, Takuto Hideyama, Hiroo Terashi, Shin Kwak, Hitoshi Aizawa
Summary: To clarify the effect of PER on sALS progression, the relationship between ALSFRS-R scores changes and serum PER concentrations was investigated. The study revealed that high concentrations of PER may worsen bulbar symptoms in patients with sALS, implying the potential benefit of measuring serum PER concentrations in these patients.
JOURNAL OF CLINICAL NEUROLOGY
(2023)
Article
Neuroimaging
Shuangwu Liu, Qingguo Ren, Gaolang Gong, Yuan Sun, Bing Zhao, Xiaotian Ma, Na Zhang, Suyu Zhong, Yan Lin, Wenqing Wang, Rui Zheng, Xiaolin Yu, Yan Yun, Dong Zhang, Kai Shao, Pengfei Lin, Ying Yuan, Tingjun Dai, Yongqing Zhang, Ling Li, Wei Li, Yuying Zhao, Peiyan Shan, Xiangshui Meng, Chuanzhu Yan
Summary: Neuroimaging studies in patients with ALS showed varying patterns of hippocampal atrophy across different disease stages. Thalamic atrophy emerged in later stages of ALS, while white matter tracts remained normal in some patients. Further studies focusing on the hippocampus in ALS patients may help clarify possible co-pathologies.
NEUROIMAGE-CLINICAL
(2021)
Article
Biochemistry & Molecular Biology
Ines Maestro, Laura R. de la Ballina, Gracia Porras, Silvia Corrochano, Eva De Lago, Anne Simonsen, Patricia Boya, Ana Martinez
Summary: Mitophagy is the process of selectively degrading mitochondria through autophagy, which prevents the accumulation of dysfunctional mitochondria and cellular degeneration. It is known to be altered in neurodegenerative diseases such as ALS. A new mitophagy inhibitor, IGS2.7, was identified and found to restore autophagy to normal levels in ALS models with mutations in SOD1 and TARDBP. This finding suggests a potential therapeutic approach for familial ALS patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Jennifer A. Fifita, Sandrine Chan Moi Fat, Emily P. McCann, Kelly L. Williams, Natalie A. Twine, Denis C. Bauer, Dominic B. Rowe, Roger Pamphlett, Matthew C. Kiernan, Vanessa X. Tan, Ian P. Blair, Gilles J. Guillemin
Summary: Tryptophan metabolism plays a significant role in the pathogenesis of ALS, with Kynurenine pathway activation and neuroinflammation being common features of various neurodegenerative diseases. Both familial and sporadic ALS have a genetic basis, with the genetic foundation of sporadic ALS being complex and involving multiple gene variants and environmental factors. The study identified novel variants in genes involved in TRP metabolism, protein synthesis, serotonin synthesis, and the KP in Australian sporadic ALS cases, providing further evidence of the involvement of TRP metabolism, the KP, and neuroinflammation in ALS disease pathobiology.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Geriatrics & Gerontology
Mubalake Yilihamu, Ji He, Xiangyi Liu, Jinzhou Tian, Dongsheng Fan
Summary: Using whole-exome sequencing, we investigated the mutation frequency of exon 4 of amyotrophic lateral sclerosis (ALS) in the new disease-causing gene GLT8D1 in Chinese patients, but found no association between GLT8D1 and ALS. Further studies are needed to confirm these findings.
NEUROBIOLOGY OF AGING
(2021)
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
Cell & Tissue Engineering
Elisa Giacomelli, Bjorn F. Vahsen, Elizabeth L. Calder, Yinyan Xu, Jakub Scaber, Elizabeth Gray, Ruxandra Dafinca, Kevin Talbot, Lorenz Studer
Summary: This article evaluates the status of using induced pluripotent stem cells (iPSCs) to model neurodegenerative diseases, focusing on amyotrophic lateral sclerosis (ALS) as an example. It discusses the methods and challenges associated with deriving and using disease-relevant neuronal and glial lineages.
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)
Editorial Material
Clinical Neurology
Lucy Farrimond, Kevin Talbot
Summary: This scientific commentary discusses the paper by Ezer et al. that investigates the infantile SOD1 deficiency syndrome caused by a homozygous SOD1 variant with a lack of enzyme activity.
Review
Clinical Neurology
Jiali Gao, Thanuja Dharmadasa, Andrea Malaspina, Pamela J. Shaw, Kevin Talbot, Martin R. Turner, Alexander G. Thompson
Summary: While elevated CK levels in ALS largely reflect lower motor neuron denervation, they are not independently associated with survival when measured during the symptomatic phase of the disease.
JOURNAL OF NEUROLOGY
(2022)
Article
Neurosciences
Sneha Pandya, Pedro D. Maia, Benjamin Freeze, Ricarda A. L. Menke, Kevin Talbot, Martin R. Turner, Ashish Raj
Summary: The study used a computational model to demonstrate a structural network-based regional pathological spread in ALS, with no simple relationship to the spatial distribution of ALS-related genes in the healthy brain. The OPTN gene was identified as a significant but weaker non-NDM contributor in the network-gene interaction model, with critical seed regions for spread within the model located in the basal ganglia, thalamus, and insula.
Article
Multidisciplinary Sciences
Sarah Burley, Dayne A. Beccano-Kelly, Kevin Talbot, Oscar Cordero Llana, Richard Wade-Martins
Summary: A study found that C9ORF72 gene expansion is associated with ALS, with immature C9-MNs exhibiting a hyperexcitable phenotype. However, this was found to be a transient phenomenon, with maturing C9-MNs showing normal electrophysiological activity.
SCIENTIFIC REPORTS
(2022)
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
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, 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)
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)