Article
Clinical Neurology
Vincenzo Di Stefano, Antonino Lupica, Paolo Alonge, Antonia Pignolo, Sofia Maria Augello, Francesca Gentile, Andrea Gagliardo, Francesca Giglia, Daniele Brinch, Maria Cappello, Daniela Di Lisi, Giuseppina Novo, Eugenia Borgione, Carmela Scuderi, Filippo Brighina
Summary: Systematic screening for ATTRv-PN can increase recognition of the disease, and unexplained weight loss associated with axonal polyneuropathy has the highest predictive value in guiding clinical suspicion.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Review
Medicine, General & Internal
Lazzaro di Biase, Alessandro Di Santo, Maria Letizia Caminiti, Pasquale Maria Pecoraro, Simona Paola Carbone, Vincenzo Di Lazzaro
Summary: Dystonia diagnosis is mainly based on clinical examination and supported by neurophysiology and genetic testing. The somatosensory temporal discrimination threshold (STDT) is the most reliable neurophysiologic measure for identifying patients with dystonia.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Clinical Neurology
Luca Angelini, Roberta Terranova, Giulia Lazzeri, Kevin R. E. van den Berg, Michiel F. Dirkx, Giulia Paparella
Summary: This review discusses the usefulness and applicability of various diagnostic methods in classifying and diagnosing tremors. Neurophysiology, laboratory and genetic tests, and neuroimaging play important roles in identifying specific tremor syndromes and etiologies. Innovative technologies show promise for clinical and research purposes.
NEUROLOGICAL SCIENCES
(2023)
Review
Neurosciences
Valeria Diaz-Pacheco, Javier Vargas-Medrano, Eric Tran, Meza Nicolas, Diamond Price, Richa Patel, Silvina Tonarelli, Bharathi S. Gadad
Summary: Mild traumatic brain injury (mTBI) is the most common type of TBI, characterized by a lack of noticeable changes in neuroimaging studies. Accurate diagnosis of mTBI is crucial due to its potential to cause post-concussion syndrome and cognitive impairments. This review focuses on the role of biomarkers in diagnosing mTBI, including protein-based markers, genetic markers, imaging markers, neurophysiological markers, and clinical trials.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Article
Clinical Neurology
Bahia Hakiki, Ida Donnini, Anna Maria Romoli, Francesca Draghi, Daniela Maccanti, Antonello Grippo, Maenia Scarpino, Antonio Maiorelli, Raisa Sterpu, Tiziana Atzori, Andrea Mannini, Silvia Campagnini, Silvia Bagnoli, Assunta Ingannato, Benedetta Nacmias, Francesco De Bellis, Anna Estraneo, Valentina Carli, Eugenia Pasqualone, Angela Comanducci, Jorghe Navarro, Maria Chiara Carrozza, Claudio Macchi, Francesca Cecchi
Summary: This study aims to investigate the rehabilitation outcomes and baseline predictive factors or biomarkers of sABI survivors to facilitate personalized rehabilitation strategies and provide accurate information to caregivers. The application and validation of machine learning algorithms can provide support tools for the clinical prognosis of sABI patients' rehabilitation pathways.
FRONTIERS IN NEUROLOGY
(2022)
Article
Psychology, Clinical
Sarah J. E. Brislin, Jessica E. M. Salvatore, Jacquelyn M. Meyers, Chella H. Kamarajan, Martin H. J. Plawecki, Howard J. Edenberg, Samuel Kuperman, Jay Tischfield, Victor P. Hesselbrock, Andrey P. B. Anokhin, David B. A. Chorlian, Marc A. I. Schuckit, John I. Nurnberger, Lance Bauer, Gayathri K. Pandey, Ashwini K. R. Pandey, John R. Kramer, Grace Chan, Bernice M. Porjesz, COGA Collaborators, Danielle M. Dick
Summary: Background: Genetic and neural risk factors for externalizing behaviors have been studied, but the relationship between genetic liability and neurophysiological risk markers is not clear. Methods: The study used data from a large family-based study and calculated polygenic scores for externalizing behaviors. Results: The study found significant associations between the polygenic scores and externalizing behaviors among both European and African ancestry participants. The study also found an inverse association between a neurophysiological marker (P3 amplitude) and externalizing behaviors among European young adults. Conclusion: The polygenic scores and P3 amplitude were independently associated with externalizing behaviors, suggesting that they may reflect different aspects of externalizing.
PSYCHOLOGICAL MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Aribert Rothenberger, Hartmut Heinrich
Summary: The co-existence of tic disorders and attention-deficit/hyperactivity disorder (TD + ADHD) is of great importance in clinical practice. This review provides an update on the neurobiological background of TD + ADHD, suggesting that it can be seen as an additive model with some overlapping aspects.
Article
Genetics & Heredity
Lama AlAbdi, Shatha Alrashseed, Ahood Alsulaiman, Rana Helaby, Faiqa Imtiaz, Mohamed Alhamed, Fowzan S. Alkuraya
Summary: The study revealed the presence of multiple AR diseases in consanguineous families, highlighting the importance of discussing the residual risk for additional AR variants when counseling for a familial AR variant. It suggests that a broader testing strategy should be considered in consanguineous couples.
GENETICS IN MEDICINE
(2021)
Editorial Material
Multidisciplinary Sciences
Scott Plevy
Summary: Mutations in the NOD2 gene are associated with an increased risk of Crohn's disease, although the exact mechanisms are not fully understood. The discovery of cell populations involved in this process opens up new possibilities for therapeutic interventions.
Article
Genetics & Heredity
Panagiotis Baliakas, Arielle R. Munters, Anders Kampe, Bianca Tesi, Marie-Louise Bondeson, Claes Ladenvall, Daniel Eriksson
Summary: Incorporating an established Polygenic Risk Score (PRS313) into clinical sequencing of women with familial breast cancer can potentially change the recommended follow-up in a significant percentage of patients. Women with breast cancer but no pathogenic variants in hereditary breast cancer genes have a higher PRS313 compared with population controls.
JOURNAL OF MEDICAL GENETICS
(2023)
Review
Biochemistry & Molecular Biology
Maxime Lemieux, Louise Thiry, Olivier D. Laflamme, Frederic Bretzner
Summary: This passage explains the regulation of the spinal locomotor circuit and the role of the cell adhesion molecule DSCAM in motor coordination. DSCAM is crucial for proper motor coordination, especially for breathing and locomotion, impacting the establishment and maintenance of motor circuits.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Clinical Neurology
Cornelis Blauwendraat, Nahid Tayebi, Elizabeth Geena Woo, Grisel Lopez, Luca Fierro, Marco Toffoli, Naomi Limbachiya, Derralynn Hughes, Vanessa Pitz, Dhairya Patel, Dan Vitale, Mathew J. Koretsky, Dena Hernandez, Raquel Real, Roy N. Alcalay, Mike A. Nalls, Huw R. Morris, Anthony H. V. Schapira, Manisha Balwani, Ellen Sidransky
Summary: This study found that PD patients with GD1 have a higher genetic risk score, suggesting that common risk variants may affect underlying biological pathways.
MOVEMENT DISORDERS
(2023)
Article
Clinical Neurology
Cornelis Blauwendraat, Nahid Tayebi, Elizabeth Geena Woo, Grisel Lopez, Luca Fierro, Marco Toffoli, Naomi Limbachiya, Derralynn Hughes, Vanessa Pitz, Dhairya Patel, Dan Vitale, Mathew J. Koretsky, Dena Hernandez, Raquel Real, Roy N. Alcalay, Mike A. Nalls, Huw R. Morris, Anthony H. V. Schapira, Manisha Balwani, Ellen Sidransky
Summary: This study investigated the contribution of PD risk variants to risk for PD in patients with GD1. The results showed that patients with GD1 who developed PD had a significantly higher PD genetic risk score than those without PD. This suggests that common risk variants may affect underlying biological pathways.
MOVEMENT DISORDERS
(2023)
Article
Clinical Neurology
Ernst Mayerhofer, Livia Parodi, Savvina Prapiadou, Rainer Malik, Jonathan Rosand, Marios K. Georgakis, Christopher D. Anderson
Summary: Integrating a genetic risk score into a clinical risk score can improve risk stratification for anticoagulation-related intracerebral hemorrhage. A prediction score incorporating genomic information is superior to a clinical risk score alone for risk stratification in anticoagulant users.
Article
Oncology
Angelica Macauda, Alyssa Clay-Gilmour, Thomas Hielscher, Michelle A. T. Hildebrandt, Marcin Kruszewski, Robert Z. Orlowski, Shaji K. Kumar, Elad Ziv, Enrico Orciuolo, Elizabeth E. Brown, Asta Forsti, Rosalie G. Waller, Mitchell J. Machiela, Stephen J. Chanock, Nicola J. Camp, Marcin Rymko, Malgorzata Rany, Wendy Cozen, Judit Varkonyi, Chiara Piredda, Matteo Pelosini, Alem A. Belachew, Edyta Subocz, Kari Hemminki, Malwina Rybicka-Ramos, Graham G. Giles, Roger L. Milne, Jonathan N. Hofmann, Jan Maciej Zaucha, Annette Juul Vangsted, Hartmut Goldschmidt, S. Vincent Rajkumar, Waldemar Tomczak, Juan Sainz, Aleksandra Butrym, Marzena Watek, Elzbieta Iskierka-Jazdzewska, Gabriele Buda, Dennis P. Robinson, Artur Jurczyszyn, Marek Dudzinski, Joaquin Martinez-Lopez, Jason P. Sinnwell, Susan L. Slager, Krzysztof Jamroziak, Rui Manuel Vieira Reis, Niels Weinhold, Parveen Bhatti, Luis G. Carvajal-Carmona, Daria Zawirska, Aaron D. Norman, Grzegorz Mazur, Sonja I. Berndt, Daniele Campa, Celine M. Vachon, Federico Canzian
Summary: This study explored the potential association between known risk variants and polygenic risk score with overall survival in multiple populations of European ancestry with multiple myeloma. The results showed that some risk SNPs were associated with overall survival, while the combined polygenic risk score did not show significant association.
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2022)
Review
Clinical Neurology
Richard Bedlack, Paul E. Barkhaus, Benjamin Barnes, Morgan Beauchamp, Tulio Bertorini, Mark B. Bromberg, Gregory T. Carter, Vinay Chaudry, Merit Cudkowicz, Ce Jackson, Gleb Levitsky, Isaac Lund, Christopher McDermott, Steven Novella, Natasha Olby, Lyle Ostrow, Gary L. Pattee, Terry Heiman-Patterson, Dylan Ratner, Kristiana Salmon, Susan Steves, Mark Terrelonge, Paul Wicks, Anne-Marie Wills
Summary: ALSUntangled reviews the effectiveness of ketogenic diets for ALS patients and finds that they may work by enhancing cellular energy balance and reducing excitotoxicity, neuroinflammation, and oxidative stress. However, there is currently insufficient data to recommend ketogenic diets for ALS patients, especially considering the potential side effects.
AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
(2023)
Article
Health Care Sciences & Services
Elizabeth Coates, Nicolo Zarotti, Isobel Williams, Sean White, Vanessa Halliday, Daniel Beever, Gemma Hackney, Theocharis Stavroulakis, David White, Paul Norman, Christopher McDermott
Summary: This study explores the barriers and enablers to increasing calorie intake in people with Amyotrophic Lateral Sclerosis (pwALS) from the perspectives of pwALS, informal carers, and healthcare professionals. The COM-B model and Theoretical Domains Framework (TDF) were used to analyze the data. The study found that all three COM-B components and eleven TDF domains are important in achieving high calorie diets in pwALS. To promote high calorie diets for pwALS, clarity around recommended diets and tailored interventions based on individual symptoms, preferences, motivations, and opportunities are needed.
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)
Review
Clinical Neurology
E. L. L. E. N. S. PIERCE, P. A. U. L. BARKHAUS, M. O. R. G. A. N. BEAUCHAMP, M. A. R. K. BROMBERG, G. R. E. G. O. R. Y. T. CARTER, J. I. L. L. GOSLINGA, D. A. V. I. D. GREELEY, S. K. Y. KIHUWA-MANI, G. L. E. B. LEVITSKY, I. S. A. A. C. LUND, C. H. R. I. S. T. O. P. H. E. R. MCDERMOTT, G. A. R. Y. PATTEE, K. A. I. T. L. Y. N. PIERCE, M. E. R. A. I. D. A. POLAK, D. Y. L. A. N. RATNER, P. A. U. L. WICKS, R. I. C. H. A. R. D. BEDLACK
Summary: Infections, such as viruses, bacteria, and parasites, have been associated with motor neuron diseases resembling ALS, with Mycobacterium avium subspecies paratuberculosis being suggested as another possible infectious cause. Treatment with antimycobacterial antibiotics has shown success in treating ALS-like symptoms, but more research is needed to establish a clear association between mycobacteria and ALS.
AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
(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
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)
Article
Multidisciplinary Sciences
Thomas H. Julian, Zain Girach, Eleanor Sanderson, Hui Guo, Jonathan Yu, Johnathan Cooper-Knock, Graeme C. Black, Panagiotis I. Sergouniotis
Summary: A 'phenome-wide' study identified 11 traits associated with primary open angle glaucoma, including certain substances in blood, intraocular pressure, diabetes, and waist circumference. Further research is expected to provide valuable insights into the effects of these traits on the development and progression of glaucoma, informing lifestyle modifications and novel therapies.
SCIENTIFIC REPORTS
(2023)
Article
Geriatrics & Gerontology
Scott P. P. Allen, Afnan Al Sultan, Elaine Kabucho Kibirige, Erin Tonkiss, Keaton J. J. Hamer, Lydia M. M. Castelli, Ya-Hui Lin, Sarah Roscoe, Nikolaos Stefanidis, Richard J. J. Mead, J. Robin Highley, Johnathan Cooper-Knock, Guillaume M. M. Hautbergue, Paul R. R. Heath, Janine Kirby, Pamela J. J. Shaw
Summary: A recent study found that truncation p.Y374X in TARDBP reduces expression of TDP43 in fibroblasts from ALS cases. In this follow-up study, we have shown that this truncation has a striking effect on the metabolic profile of fibroblasts. Phenotypic metabolic screening revealed distinct metabolic alterations in TDP43-Y374X fibroblasts, including changes in key metabolic intermediates. These findings suggest that TDP43 truncation directly impairs glycolytic and mitochondrial function, indicating potential therapeutic targets for mitigating its effects.
FRONTIERS IN AGING NEUROSCIENCE
(2023)
Article
Clinical Neurology
Allison A. Dilliott, Ahmad Al Nasser, Marwa Elnagheeb, Jennifer Fifita, Lyndal Henden, Ingrid M. Keseler, Steven Lenz, Heather Marriott, Emily Mccann, Maysen Mesaros, Sarah Opie-Martin, Emma Owens, Brooke Palus, Justyne Ross, Zhanjun Wang, Hannah White, Ammar Al-Chalabi, Peter M. Andersen, Michael Benatar, Ian Blair, Johnathan Cooper-Knock, Elizabeth A. Harrington, Jeannine Heckmann, John Landers, Cristiane Moreno, Melissa Nel, Evadnie Rampersaud, Jennifer Roggenbuck, Guy Rouleau, Bryan Traynor, Marka Van Blitterswijk, Wouter Van Rheenen, Jan Veldink, Jochen Weishaupt, Luke Drury, Matthew B. Harms, Sali M. K. Farhan
Summary: The establishment of the Clinical Genome Resource (ClinGen) amyotrophic lateral sclerosis (ALS) spectrum disorders Gene Curation Expert Panel (GCEP) aimed to evaluate the strength of evidence for genes associated with ALS. This study assessed the heterogeneity in clinical genetic testing panels for ALS and found variability in the genes included, suggesting the need for consensus on gene inclusions to improve diagnostic yields and reduce missed diagnoses. The findings highlight the importance of standardized guidance for laboratories and better application of genetic testing for ALS patients and their families.
AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
(2023)
Article
Clinical Neurology
S. Wheelwright, R. Maunsell, S. Taylor, N. Drinkwater, C. Erridge, C. Foster, M. Hardcastle, A. Hogden, I. Lawson, D. Lisiecka, C. Mcdermott, K. E. Morrison, C. Muir, A. Recio-Saucedo, S. White
Summary: A web-based patient decision aid (PDA) was developed and tested to support people with motor neurone disease (plwMND) considering gastrostomy tube placement. The PDA went through iterative improvement based on user feedback and evaluation by plwMND and healthcare professionals (HCPs). The results showed that the PDA was well-received by users and considered valuable for the decision-making process.
AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
(2023)
Article
Clinical Neurology
Robert McFarlane, Miriam Galvin, Mark Heverin, Eanna Mac Domhnaill, Deirdre Murray, Dara Meldrum, Peter Bede, Anthony Bolger, Lucy Hederman, Sinead Impey, Gaye Stephens, Ciara O'Meara, Vincent Wade, Ammar Al Chalabi, Adriano Chio, Phillippe Corcia, Philip van Damme, Caroline Ingre, Christopher McDermott, Monica Povedanos, Leonard Van den Berg, Orla Hardiman
AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
(2023)
Article
Clinical Neurology
Eilis Conroy, Beatriz Velez-Gomez, David O'Brien, Mark Heverin, Orla Hardiman, Christopher Mcdermott, Miriam Galvin
Summary: The IMPACT-ALS survey collected the experiences of people living with ALS across nine European countries. The survey provided insights into the burden of the disease and the opinions of the patients on person-centered therapies. The data analysis revealed symptoms, fears, lifestyle changes, and expectations for future therapies among the respondents.
AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
(2023)
Review
Clinical Neurology
Namita A. Goyal, Kerina Bonar, Natasa Savic, Raphaelle Beau Lejdstrom, Jack Wright, Jennifer Mellor, Christopher Mcdermott
Summary: Misdiagnosis of ALS is common, leading to a lengthy diagnostic pathway. Targeted education for patients and physicians is needed to increase awareness of symptoms and the benefits of prompt referral to multidisciplinary care.
AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
(2023)