Article
Clinical Neurology
Gina Sangha, Bohao Yao, Daniel Lunn, Iwona Skorupinska, Louise Germain, Damian Kozyra, Matt Parton, James Miller, Michael G. Hanna, David Hilton-Jones, Jane Freebody, Pedro M. Machado
Summary: This study observed the decline in muscle strength and physical function in patients with sporadic inclusion body myositis (IBM), finding that MMT, QMT, and IBMFRS scores decreased annually, with a steeper decline in the initial years. Older age of onset was associated with a more rapid IBMFRS decline and time to using a mobility aid was influenced by age.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2021)
Article
Medicine, General & Internal
Antonella Tramutola, Hannah S. Bakels, Federica Perrone, Michela Di Nottia, Tommaso Mazza, Maria Pia Abruzzese, Martina Zoccola, Sara Pagnotta, Rosalba Carrozzo, Susanne T. de Bot, Marzia Perluigi, Willeke M. C. van Roon-Mom, Ferdinando Squitieri
Summary: This study investigated the expression levels of two main glucose transporters, GLUT-1 and GLUT-3, in patients with paediatric Huntington disease with highly expanded mutations (HE-PHD). The results showed significantly lower expression of GLUT-1 and GLUT-3 in the frontal cortex of HE-PHD patients. The study also found deregulated mitochondrial complex expression and reduced hexokinase-II expression in HE-PHD patients, indicating a dysfunctional hypometabolic state in the brains of paediatric Huntington disease.
Review
Hematology
Jean-Louis Gueant, Rosa-Maria Gueant-Rodriguez, Abderrahim Oussalah, Stephane Zuily, Irwin Rosenberg
Summary: Thromboembolic manifestations are common in patients with severe hyperhomocysteinemia related to inherited disorders and deficiencies in vitamin B12 and folate. However, moderate hyperhomocysteinemia is only a modest predictor of cardiovascular risk. The recognition of homocysteine as a cardiovascular risk factor has been challenged by some studies, but not all randomized clinical trials have reached the same conclusion.
THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Multidisciplinary Sciences
Igor Koval, Thomas Dighiero-Brecht, Allan J. Tobin, Sarah J. Tabrizi, Rachael Scahill, Sophie Tezenas du Montcel, Stanley Durrleman, Alexandra Durr
Summary: This study utilizes disease course mapping to forecast biomarker progression for individual carriers of the pathological CAG repeat expansions responsible for Huntington disease, in order to select participants at risk for progression and compute the power of trials for such an enriched population, ultimately reducing sample sizes and ensuring a more homogeneous group of participants.
SCIENTIFIC REPORTS
(2022)
Article
Clinical Neurology
Pierre Wibawa, Mark Walterfang, Charles B. B. Malpas, Yifat Glikmann-Johnston, Govinda Poudel, Adeel Razi, Anthony J. J. Hannan, Dennis Velakoulis, Nellie Georgiou-Karistianis
Summary: This study examined the volumes of hippocampal subfields in individuals with early symptomatic Huntington disease (HD) using T1-weighted MRI. The results showed significantly lower subfield volumes in the symptomatic HD group compared to the pre-symptomatic HD and control groups. These findings suggest the involvement of specific hippocampal subregions in the memory impairment observed in early symptomatic HD.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Immunology
Kui Zhang, Yan Zheng, Qing Han, Ying Liu, Weitao Wang, Jin Ding, Yan Wang, Bei Zhang, Junfeng Jia, Minwen Zheng, Zhaohui Zheng, Ping Zhu
Summary: The study demonstrated that TNF-α inhibitors significantly improved both clinical and MRI manifestations of hip involvement in patients with SpA, showing greater efficacy compared to the control group at 52 weeks. Quantitative MRI assessment combined with clinical evaluation can be utilized to accurately assess the treatment effect of TNF-α inhibitors in SpA patients with hip involvement.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Health Care Sciences & Services
Sabrina Maffi, Eugenia Scaricamazza, Simone Migliore, Melissa Casella, Consuelo Ceccarelli, Ferdinando Squitieri
Summary: This study investigated the correlations between sleep features and motor, cognitive, behavioral, and functional changes in individuals with Huntington's disease (HD). The results showed a significant association between sleep abnormalities and the severity of disease progression, as well as impaired independence, cognitive performance, and motor functions. Sleep abnormalities are an important aspect of the clinical profile of HD and can greatly impact patients' quality of life.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Review
Clinical Neurology
Kirsi M. Kinnunen, Ariana P. Mullin, Dorian Pustina, Emily C. Turner, Jackson Burton, Mark F. Gordon, Rachael Scahill, Emily C. Gantman, Simon Noble, Klaus Romero, Nellie Georgiou-Karistianis, Adam J. Schwarz
Summary: Volumetric magnetic resonance imaging (vMRI) is widely used in Huntington's disease (HD) research to assess brain atrophy, but there is a lack of standardization and accessible datasets. Recommendations for standardized practices, advanced methodologies evaluation, defining anatomical boundaries, and broad data access aim to enhance understanding of disease progression and confidence in using vMRI for drug development.
FRONTIERS IN NEUROLOGY
(2021)
Letter
Clinical Neurology
Deepa Dash, Tiago A. Mestre
Summary: We present a case of a 68-year-old lady who had symptoms resembling Huntington's disease but was genetically diagnosed with Spinocerebellar ataxia (SCA)17. MRI Brain showed the presence of motor band sign, which is typically seen in motor neuron disease. This case highlights the expanding spectrum of radiological signs associated with SCA 17.
PARKINSONISM & RELATED DISORDERS
(2023)
Article
Pharmacology & Pharmacy
Libor Fila, Alzbeta Grandcourtova, Alena Bilkova, Pavel Drevinek
Summary: A single center trial showed that CF patients who were ineligible for clinical trials experienced improvement in lung function and nutritional status after ETI treatment. However, those with severe airway obstruction or well-preserved lung function had a smaller increase in ppFEV(1).
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Orthopedics
Alvaro Reyes, Danielle M. Bartlett, Timothy J. Rankin, Pauline Zaenker, Kate Turner, Wei-Peng Teo, Shih Ching Fu, Josefa Domingos, Nellie Georgiou-Karistianis, Mel Ziman, Travis M. Cruickshank
Summary: Dual-tasking deficiencies are common in people with premanifest Huntington disease and may be influenced by poor sleep quality. Measures of dual-tasking show acceptable test-retest reliability in this population and should be considered when managing dual-tasking problems.
Review
Pharmacology & Pharmacy
Xue Wang, Courtney Bishop, James O'Callaghan, Ali Gayhoor, Justin Albani, Wendy Theriault, Michael Chappell, Xavier Golay, Danny Wang, Lino Becerra
Summary: Neurodegenerative mechanisms affect the brain through changes in structure and physiology. Cerebral blood flow (CBF) is a challenging biomarker to harmonize for clinical trials. Arterial spin labeling (ASL) perfusion MRI is a promising method for quantifying CBF without contrast agents and has been increasingly applied in clinical trials. This review presents ASL MRI techniques, implementation strategies, confidence levels in assessing disease progression and treatment effects, and image analysis details.
DRUG DISCOVERY TODAY
(2023)
Review
Gastroenterology & Hepatology
Paul Y. Kwo, Tushar Patel
Summary: Clinical trials are crucial for advancing new therapies for liver diseases and adapting to emerging capabilities and external forces. The COVID-19 pandemic has prompted changes in clinical trial operations and opportunities for innovation in hepatology trials. Technological advances will drive future trials, incorporating digital capabilities and expanded data collection, computing, and analytics. Innovative trial designs and broader participant engagement will shape trial conduct, along with evolving regulatory needs and new stakeholders. The evolution of clinical trials presents unique opportunities to improve the lives of patients with liver diseases.
Review
Medicine, Research & Experimental
Shreya Asher, Ronny Priefer
Summary: This article reviews the history of clinical trials for Alzheimer's disease and analyzes the reasons for their failures.
Article
Clinical Neurology
Beate Schumann-Werner, Imis Dogan, Shahram Mirzazade, Bettina Mall, Rena Overbeck, Philipp Honrath, Jorg B. Schulz, Kathrin Reetz, Cornelius J. Werner
Summary: This study provides a comprehensive investigation of dysphagia in Huntington disease, revealing a communication disorder between sensory and motor networks involved in swallowing. The study also emphasizes the importance of early instrumental swallowing evaluation.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Article
Clinical Neurology
Jordan L. Schultz, Douglas R. Langbehn, Hend M. Al-Kaylani, Ellen van der Plas, Timothy R. Koscik, Eric A. Epping, Patricia B. Espe-Pfeifer, Erin P. Martin, David J. Moser, Vincent A. Magnotta, Peggy C. Nopoulos
Summary: This study aimed to quantify disease progression in juvenile-onset Huntington's disease (JOHD) and explore its application in clinical trials. The results demonstrate that structural brain imaging and clinical measures in JOHD may serve as potential biomarkers of disease progression.
MOVEMENT DISORDERS
(2023)
Article
Neurosciences
Zachary A. A. Stoebner, Kilian Hett, Ilwoo Lyu, Hans Johnson, Jane S. S. Paulsen, Jeffrey D. D. Long, Ipek Oguz
Summary: In addition to the striatum, cortical alterations caused by Huntington's disease have been found, but there is inconsistency in using cortical thickness as a metric. This study proposes a comprehensive approach using cortical thickness, sulcal depth, and local gyrification index, and the results are consistent with prior findings while highlighting the complementary nature of these measures.
HUMAN BRAIN MAPPING
(2023)
Review
Clinical Neurology
Patrick W. Cullinane, Eduardo de Pablo Fernandez, Annekatrin Konig, Tiago Fleming Outeiro, Zane Jaunmuktane, Thomas T. Warner
Summary: Highly reproducible epidemiological evidence suggests that type 2 diabetes (T2D) increases the risk and progression of Parkinson's disease (PD) and repurposing certain antidiabetic medications for PD treatment shows promise. The high prevalence of T2D highlights the need for personalized antidiabetic treatment in PD patients. However, understanding the mechanistic relation and molecular pathways affected by T2D in the brain is essential. The review focuses on the evidence of T2D-associated dysregulation in peripheral and brain pathways, its impact on neurodegeneration in PD, and the challenges in unraveling the complex relationship between T2D, insulin resistance, and PD.
MOVEMENT DISORDERS
(2023)
Article
Clinical Neurology
Sasivimol Virameteekul, Tamas Revesz, Zane Jaunmuktane, Thomas T. Warner, Eduardo De Pablo-Fernandez
Summary: The recent MDS-MSA diagnostic criteria have been validated against neuropathological diagnosis and shown excellent diagnostic performance. They outperformed previous criteria and clinical diagnosis, demonstrating their usefulness in clinical practice and research.
MOVEMENT DISORDERS
(2023)
Article
Clinical Neurology
Sasivimol Virameteekul, Tamas Revesz, Zane Jaunmuktane, Thomas T. Warner, Eduardo De Pablo-Fernandez
Summary: This study retrospectively analyzed the clinical diagnostic accuracy data of patients with Parkinson's disease confirmed by neuropathology between 2009 and 2019. The results showed a significant improvement in clinical diagnostic accuracy of Parkinson's disease over the past decade, especially in early stages. The diagnosis by movement disorder experts remains the "gold standard" for Parkinson's disease during life.
MOVEMENT DISORDERS
(2023)
Letter
Clinical Neurology
Yasuo Miki, Conceicao Bettencourt, Zane Jaunmuktane, Janice L. Holton, Thomas T. Warner, Koichi Wakabayashi
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2023)
Article
Neurosciences
Daniel Ramandi, Nicholas J. Michelson, Lynn A. Raymond, Timothy H. Murphy
Summary: This study developed a method for simultaneous mesoscale cortical imaging and subcortical fiber photometry recording, which allows the study of neuronal activity. The results showed a high correlation between cortical and striatal activity in response to sensory stimulation or movement. This method can provide insights into the cell-specific connectivity in the corticobasal ganglia circuit organization.
Article
Neurosciences
Yundi Wang, Marja D. Sepers, Dongsheng Xiao, Lynn A. Raymond, Timothy H. Murphy
Summary: This study developed a high-throughput water-reaching task and training protocol to monitor forelimb impairment and cortical changes in HD mice. The results showed that HD mice took longer to learn the event sequence and displayed reduced cortical activity associated with successful reaches. Over time, cortical activity increased and reaching trajectories became longer and more variable in HD mice. This study provides insights into the onset and manifestation of movement disorders, therapeutic intervention windows, and testing of drug efficacy.
Article
Clinical Neurology
Patrick W. Cullinane, Katie Sidle, Kailash P. Bhatia, Tamas Revesz, Thomas T. Warner
Summary: Globular glial tauopathies (GGTs) are a rare group of neurodegenerative diseases. Recent research supports the idea that GGT should be considered as a separate entity within neuropathology. We present a case of sporadic GGT type II and discuss the clinical features and molecular pathophysiology. Increased awareness of this condition is important as GGT patients may be eligible for ongoing clinical trials of anti-tau therapies.
PRACTICAL NEUROLOGY
(2023)
Article
Clinical Neurology
Duncan Street, Edwin Jabbari, Alyssa Costantini, P. Simon Jones, Negin Holland, Timothy Rittman, Marte T. Jensen, Viorica Chelban, Yen Y. Goh, Tong Guo, Amanda J. Heslegrave, Federico Roncaroli, Johannes C. Klein, Olaf Ansorge, Kieren S. J. Allinson, Zane Jaunmuktane, Tamas Revesz, Thomas T. Warner, Andrew J. Lees, Henrik Zetterberg, Lucy L. Russell, Martina Bocchetta, Jonathan D. Rohrer, David J. Burn, Nicola Pavese, Alexander Gerhard, Christopher Kobylecki, P. Nigel Leigh, Alistair Church, Michele T. M. Hu, Henry Houlden, Huw Morris, James B. Rowe
Summary: The study compares candidate clinical trial end points in progressive supranuclear palsy, multiple system atrophy, corticobasal syndrome and related disorders. Neuroimaging metrics generally require smaller sample sizes than cognitive and functional measures, but the optimal outcome measures differ by disease type.
Article
Clinical Neurology
Timothy R. Koscik, Ellen van der Plas, Jeffrey D. Long, Stephen Cross, Laurie Gutmann, Sarah A. Cumming, Darren G. Monckton, Richard K. Shields, Vincent Magnotta, Peggy C. Nopoulos
Summary: This study compared the changes in white matter microstructure, functional measures, and clinical symptoms in patients with myotonic dystrophy type 1. The results showed that indices of white matter health were associated with functional performance and could accurately reflect disease progression. These findings are crucial for the design of clinical trials.
NEUROMUSCULAR DISORDERS
(2023)
Review
Neurosciences
Katherine Fodder, Rohan de Silva, Thomas T. Warner, Conceicao Bettencourt
Summary: Neurodegenerative diseases are a group of heterogeneous conditions involving the progressive degeneration of the central or peripheral nervous systems. The underlying mechanisms are not completely understood, but protein aggregation in the brain, such as β-amyloid plaques in Alzheimer's disease and α-synuclein in Parkinson's disease, plays a central role. Dysfunctional oligodendrocytes and myelin loss are increasingly implicated in disease pathogenesis, with aberrant DNA methylation in oligodendrocyte-related genes being recently highlighted. Elucidating the involvement of DNA methylation in neurodegenerative diseases and specific cell types like oligodendrocytes may offer therapeutic opportunities, as DNA methylation is reversible.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Article
Psychology, Biological
Sobanawartiny Wijeakumar, Samuel H. Forbes, Vincent A. Magnotta, Sean Deoni, Kiara Jackson, Vinay P. Singh, Madhuri Tiwari, Aarti Kumar, John P. Spencer
Summary: Stunting in infancy has a negative impact on visual working memory and attention in infants, affecting their long-term cognitive outcomes. Intervention efforts should focus on improving working memory and reducing distractibility in infancy.
NATURE HUMAN BEHAVIOUR
(2023)
Article
Neurosciences
Victoria A. Mueller Ewald, Jessica R. Purnell, Joel E. Bruss, Ercole J. Barsotti, Amro S. Aldine, Kurayi G. Mahachi, John A. Wemmie, Vincent A. Magnotta, Aaron D. Boes, Krystal L. Parker, Jess G. Fiedorowicz
Summary: This study found a higher incidence of posterior fossa arachnoid cysts (PFACs) in bipolar disorder patients and suggested that those with PFACs may have milder symptoms. The findings align with prior research and suggest an association between PFACs and psychiatric symptoms.