Article
Genetics & Heredity
Hye Jin Kim, Sang Beom Kim, Hyun Su Kim, Hye Mi Kwon, Jae Hong Park, Ah Jin Lee, Si On Lim, Soo Hyun Nam, Young Bin Hong, Ki Wha Chung, Byung-Ok Choi
Summary: Charcot-Marie-Tooth disease (CMT) is a common hereditary peripheral neuropathy. This study analyzed the genetic sequences of 1,143 Korean CMT families and identified 10 NEFL mutations. NEFL-related CMT patients showed diverse clinical phenotypes, including ataxia and dysphagia. The findings of this study could aid in the evaluation of novel NEFL variants and differential diagnosis of CMT subtypes.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2022)
Article
Neurosciences
Daniel S. Peterson, Allison Moore, Edward Ofori
Summary: In individuals with Charcot-Marie-Tooth disease, gait outcomes change significantly with fatigue, correlating with general life satisfaction but not perceived fatigue. This suggests performance fatigability during gait could be a target for rehabilitation for individuals with Charcot-Marie-Tooth disease.
Review
Biochemistry & Molecular Biology
Marina Stavrou, Irene Sargiannidou, Elena Georgiou, Alexia Kagiava, Kleopas A. Kleopa
Summary: CMT disease is a genetically heterogeneous disorder affecting the peripheral nerves, with diverse molecular genetic mechanisms discovered over the past three decades. There are currently various treatment approaches in preclinical testing and clinical trials, including disease-specific targeted therapies and treatments targeting common pathways shared by different CMT types. As promising treatments advance to clinical translation, optimizing outcome measures, novel biomarkers, and appropriate trial designs are crucial to facilitate successful testing and validation of novel treatments for CMT patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Clinical Neurology
Rafael Sivera, Vincenzo Lupo, Marina Frasquet, Herminia Argente-Escrig, Jorge Alonso-Perez, Jordi Diaz-Manera, Luis Querol, Maria del Mar Garcia-Romero, Samuel Ignacio Pascual, Tania Garcia-Sobrino, Carmen Paradas, Juan Francisco Vazquez-Costa, Nuria Muelas, Elvira Millet, Juan Jesus Vilchez, Carmen Espinos, Teresa Sevilla
Summary: This study identified 15 patients with CMT2Z caused by MORC2 mutations in Spain, with most exhibiting a scapuloperoneal phenotype and a few showing a neurodevelopmental phenotype. The findings suggest a diverse spectrum of disease characteristics and clinical presentations.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Article
Cell Biology
Cara R. Schiavon, Gerald S. Shadel, Uri Manor
Summary: CMT disease is a progressive, inherited neurological disorder associated with mutations in at least 80 different genes. Clinical manifestations typically involve peripheral neurons, with some mutations potentially leading to mitochondrial mobility defects, suggesting a common underlying disease mechanism.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Genetics & Heredity
Yuji Okamoto, Hiroshi Takashima
Summary: Charcot-Marie-Tooth disease (CMT) is the most common genetically transmitted neuromuscular condition without effective pharmacological treatments. The genetic heterogeneity of CMT poses a significant barrier to comprehensive therapies. This review discusses prospective therapeutic strategies for common CMT variants and evaluates the progress in gene therapy techniques, which have the potential to advance future research.
Review
Pharmacology & Pharmacy
Karen Libberecht, Tim Vangansewinkel, Ludo Van Den Bosch, Ivo Lambrichts, Esther Wolfs
Summary: This article reviews the role of protein quality control systems in CMT1 and introduces potential treatment strategies to restore proteostasis.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Clinical Neurology
Adriana P. Rebelo, Andrea Cortese, Amit Abraham, Yael Eshed-Eisenbach, Gal Shner, Anna Vainshtein, Elena Buglo, Vladimir Camarena, Gabriel Gaidosh, Ramin Shiekhattar, Lisa Abreu, Steve Courel, Dennis K. Burns, Yunhong Bai, Chelsea Bacon, Shawna M. E. Feely, Diana Castro, Elior Peles, Mary M. Reilly, Michael E. Shy, Stephan Zuchner
Summary: The CADM family of proteins mediate direct contact and interaction between axons and glia, with mutations in CADM3 potentially causing abnormal axon-glia interaction and disease manifestation in CMT patients.
Article
Clinical Neurology
Ru-Ying Yuan, Zi-Ling Ye, Xiao-Rong Zhang, Liu-Qing Xu, Jin He
Summary: The study confirmed SORD mutations as a causative factor for CMT and expanded the mutational and phenotypic spectrum of SORD-related CMT.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2021)
Article
Clinical Neurology
Marta Bellofatto, Alessandro Bertini, Irene Tramacere, Fiore Manganelli, Gian Maria Fabrizi, Angelo Schenone, Lucio Santoro, Tiziana Cavallaro, Marina Grandis, Stefano C. Previtali, Yuri Falzone, Isabella Allegri, Luca Padua, Costanza Pazzaglia, Daniela Calabrese, Paola Saveri, Aldo Quattrone, Paola Valentino, Stefano Tozza, Luca Gentile, Massimo Russo, Anna Mazzeo, Giuseppe Vita, Sylvie Piacentini, Chiara Pisciotta, Davide Pareyson
Summary: This study investigated fatigue in CMT patients and found that 36% of the patients experienced abnormal fatigue. Abnormal fatigue was correlated with disease severity, anxiety, depression, sleepiness, and obesity. Therefore, the management of CMT patients should involve treating fatigue and addressing other factors such as anxiety, depression, sleepiness, and obesity.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Elena Abati, Stefania Magri, Megi Meneri, Giulia Manenti, Daniele Velardo, Francesca Balistreri, Chiara Pisciotta, Paola Saveri, Nereo Bresolin, Giacomo Pietro Comi, Dario Ronchi, Davide Pareyson, Franco Taroni, Stefania Corti
Summary: This study identified two cases of biallelic HSPB1 p.S135F and p.R136L mutations in two families, confirming their association with severe CMT2F/dHMN and a strictly dominant inheritance pattern.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2021)
Article
Clinical Neurology
Marta Bellofatto, Alessandro Bertini, Irene Tramacere, Fiore Manganelli, Gian Maria Fabrizi, Angelo Schenone, Lucio Santoro, Tiziana Cavallaro, Marina Grandis, Stefano C. Previtali, Yuri Falzone, Isabella Allegri, Luca Padua, Costanza Pazzaglia, Daniela Calabrese, Paola Saveri, Aldo Quattrone, Paola Valentino, Stefano Tozza, Luca Gentile, Massimo Russo, Anna Mazzeo, Giuseppe Vita, Sylvie Piacentini, Chiara Pisciotta, Davide Pareyson
Summary: This study investigated the presence of fatigue and its correlations in Charcot-Marie-Tooth disease (CMT). The results showed that 36% of the patients had abnormal fatigue, which was correlated with disease severity, anxiety, depression, sleepiness, and obesity. Therefore, the management of CMT patients should include treatment for fatigue and its different generators.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Clinical Neurology
Matthew J. Jennings, Alexia Kagiava, Leen Vendredy, Emily L. Spaulding, Marina Stavrou, Denisa Hathazi, Anika Gruneboom, Vicky De Winter, Burkhard Gess, Ulrike Schara, Oksana Pogoryelova, Hanns Lochmuller, Christoph H. Borchers, Andreas Roos, Robert W. Burgess, Vincent Timmerman, Kleopas A. Kleopa, Rita Horvath
Summary: By studying the proteins in the serum of CMT patients and mouse models, potential biomarkers for CMT are identified, which can be used to assess disease severity and track treatment effects. In addition, elevation of complement proteins in CMT suggests a potential therapeutic target.
Article
Clinical Neurology
Marta Bellofatto, Luca Gentile, Alessandro Bertini, Irene Tramacere, Fiore Manganelli, Gian Maria Fabrizi, Angelo Schenone, Lucio Santoro, Tiziana Cavallaro, Marina Grandis, Stefano Previtali, Marina Scarlato, Isabella Allegri, Luca Padua, Costanza Pazzaglia, Flavio Villani, Eleonora Cavalca, Paola Saveri, Aldo Quattrone, Paola Valentino, Stefano Tozza, Massimo Russo, Anna Mazzeo, Giuseppe Vita, Sylvie Piacentini, Giuseppe Didato, Chiara Pisciotta, Davide Pareyson, CMT Network
Summary: This study investigated the presence of sleep abnormalities in Charcot-Marie-Tooth disease (CMT) patients and their correlation with disease severity and characteristics. The results showed that CMT patients had poor sleep quality and daytime somnolence, which were associated with anxiety, depression, and fatigue.
JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Feride Cinarli Yuksel, Paschalis Nicolaou, Kerri Spontarelli, Maike F. Dohrn, Adriana P. Rebelo, Pantelitsa Koutsou, Anthi Georghiou, Pablo Artigas, Stephan L. Zuchner, Kleopas A. Kleopa, Kyproula Christodoulou
Summary: This study reports the first case of demyelinating Charcot-Marie-Tooth disease caused by a novel variant in the ATP1A1 gene. Functional analysis showed significantly reduced expression levels of ATP1A1 and ATP1B1 in the patient, as well as decreased cell viability in vitro. These findings further support the causative role of ATP1A1 in peripheral neuropathy and expand the mutational and phenotypic spectrum of ATP1A1-associated CMT.
JOURNAL OF NEUROLOGY
(2023)
Article
Orthopedics
Leanne N. Dwan, Paul Gibbons, Kamal Jamil, David Little, Oliver Birke, Manoj P. Menezes, Joshua Burns
Summary: This study identified reliable and sensitive radiographic measures for hip dysplasia in children with Charcot-Marie-Tooth disease, which can be prioritized for hip screening to mitigate the deleterious effects of hip dysplasia, pain, and disability in adulthood.
Article
Neurosciences
Jianhua Lin, Mark Halaki, Andrew Leaver
Summary: This study aimed to investigate whether gait is altered in people with low back pain (LBP) when sex, age, height, and walking speed are controlled. A series of gait parameters were measured in 16 participants with LBP and 16 age, sex, and height matched healthy controls. The results showed significant between-group differences in stride length mean during matched speed walking and single support phase standard deviation during comfortable speed walking, suggesting that gait is not altered in individuals with mild LBP when sex, age, and height are controlled.
Article
Clinical Neurology
Penelope Monroe, Mark Halaki, Georgina Luscombe, Fiona Kumfor, Kirrie J. Ballard
Summary: This study aimed to determine the feasibility and acceptability of the MuSiCON choir and language/communication assessment protocol for individuals with cognitive impairment. The results showed that most participants had a positive response to MuSiCON, perceiving improved daily functioning and high therapeutic benefit without harmful effects. However, there was no reliable change in communication skills. The MuSiCON protocol was well received by participants and staff at the residential facility.
Article
Neurosciences
Shaun Abbott, Daniel Ibarcena, Tom Gwinn, Artur Struzik, Mark Halaki, Gurleen Kaloti, James Salter, Stephen Cobley
Summary: The purpose of this study was to investigate the relationship between average growth tempo, maturity status, and coordination capability using a hopping task. The results showed that short-term accelerations in growth tempo were associated with temporary disruptions to movement coordination capability. By measuring growth tempo and using specific movement tasks, disturbances in motor coordination can be consistently identified.
HUMAN MOVEMENT SCIENCE
(2023)
Review
Clinical Neurology
Mary M. Reilly, David N. Herrmann, Davide Pareyson, Steven S. Scherer, Richard S. Finkel, Stephan Zuechner, Joshua Burns, Michael E. Shy
Summary: Heritable neurological disorders provide insights into disease mechanisms, facilitating the development of novel therapeutic approaches. The challenges of measuring disease progression in rare and slowly progressive neurogenetic diseases are addressed through the development of clinical outcome assessments and disease biomarkers in inherited peripheral neuropathies. It is proposed that carefully developed biomarkers from imaging, plasma, or skin can predict meaningful progression in functional and patient-reported outcome assessments, enabling feasible clinical trials within a shorter duration for these rare and ultra-rare disorders.
ANNALS OF NEUROLOGY
(2023)
Letter
Clinical Neurology
Katy Eichinger, Steffen E. Behrens-Spraggins, Janet Sowden, Davide M. Pareyson, Mary S. Reilly, Steven E. Scherer, Michael N. Shy, David Herrmann
JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM
(2023)
Article
Clinical Neurology
Tong Tong Wu, Richard S. S. Finkel, Carly E. E. Siskind, Shawna M. E. Feely, Joshua Burns, Mary M. M. Reilly, Francesco Muntoni, Timothy Estilow, Michael E. E. Shy, Sindhu Ramchandren
Summary: This study developed and validated the parent-proxy version of the pCMT-QOL outcome measure for children aged 8 to 18 with CMT, which is a reliable and valid measure of health-related QOL.
JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM
(2023)
Article
Clinical Neurology
Tong Tong Wu, Richard Finkel, Carly E. Siskind, Shawna M. E. Feely, Joshua Burns, Mary M. Reilly, Francesco Muntoni, Evelin Milev, Timothy Estilow, Michael E. Shy, Sindhu Ramchandren
Summary: The objective of this study was to evaluate the parent-proxy version of the pediatric Charcot Marie Tooth specific quality of life (pCMT-QOL) outcome instrument for children aged 7 or younger with CMT. The parent-proxy version of the pCMT-QOL outcome measure, known as the pCMT-QOL (0-7 years parent-proxy), was validated as a valid and sensitive proxy measure of health-related quality of life for children aged 0-7 years with CMT.
JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM
(2023)
Article
Clinical Neurology
Lorenzo Nanetti, Stefania Magri, Mario Fichera, Anna Castaldo, Anna Nigri, Chiara Pinardi, Alessia Mongelli, Lidia Sarro, Davide Pareyson, Marina Grisoli, Cinzia Gellera, Daniela Di Bella, Caterina Mariotti, Franco Taroni
Summary: This study identified a form of spinocerebellar ataxia (SCA) characterized by the presence of an intermediate-length expansion in the TATA-box binding protein gene (TBP40-46) and a pathogenic variant in the Stip1-homologous and U-Box containing protein 1 gene (STUB1), representing the first example of digenic inheritance in a cerebellar disorder. Patients with SCA(TBP/STUB1) exhibited multi-domain dementia and more severe impairment compared to those carrying only fully expanded SCA17 alleles. Neuroimaging analysis revealed reduced cerebellar volume and thickness in SCA(TBP/STUB1) patients, as well as basal ganglia volume reduction in both patient groups. The findings have implications for diagnosis and genetic counseling in families with hereditary and sporadic ataxia.
MOVEMENT DISORDERS
(2023)
Article
Rehabilitation
Enza Leone, Sally Davenport, Claire Robertson, Matilde Laura, Mariola Skorupinska, Mary M. Reilly, Gita Ramdharry
Summary: This study aimed to determine the incidence of PF dislocation in adults with CMT and explore the risk factors associated with it. The results showed that PF dislocation was common in CMT patients and was associated with multiple risk factors.
PHYSIOTHERAPY RESEARCH INTERNATIONAL
(2023)
Article
Cell Biology
Hyun Sung, Thomas E. Lloyd
Summary: Macroautophagy is crucial for eliminating protein aggregates and damaged organelles, and its dysregulation is implicated in neurodegenerative diseases like ALS and FTD. The expansion of G4C2 repeats in the C9orf72 gene disrupts autophagosome formation, highlighting the importance of dynamic ER tubules.
Article
Clinical Neurology
Gabrielle A. Donlevy, Kayla M. D. Cornett, Sarah P. Garnett, Rosemary Shy, Timothy Estilow, Sabrina W. Yum, Kimberly Anderson, Davide Pareyson, Isabella Moroni, Francesco Muntoni, Mary M. Reilly, Richard S. Finkel, David N. Herrmann, Katy J. Eichinger, Michael E. Shy, Joshua Burns, Manoj P. Menezes
Summary: This study aimed to evaluate the impact of body mass index (BMI) on disease progression in children with Charcot-Marie-Tooth disease (CMT) over a period of 2 years. The results showed that children with CMT who were underweight or obese exhibited greater disability. It suggests that interventions to maintain or improve BMI towards a healthy weight may reduce disability in children with CMT.
Review
Clinical Neurology
Chiara Pisciotta, Davide Pareyson
Summary: Currently, there is no effective drug treatment available for Charcot-Marie-Tooth disease (CMT). Current management relies on rehabilitation therapy, surgery, and symptomatic treatment. Several approaches, including gene therapy and compounds targeting specific pathways, are being investigated as potential disease-modifying therapies. Correcting metabolic abnormalities is also a focus of research.
NEUROMUSCULAR DISORDERS
(2023)
Review
Sport Sciences
Timothy McNally, Suzi Edwards, Mark Halaki, Nicholas O'Dwyer, Tania Pizzari, Sarah Blyton
Summary: This study focused on hamstring strain injury (HSI) in sports and conducted a systematic search and meta-analysis. The findings revealed that high-intensity running increases hamstring activation and kinetic demands. These results can provide objective measures for clinicians in designing injury prevention and return-to-play strategies.
SCANDINAVIAN JOURNAL OF MEDICINE & SCIENCE IN SPORTS
(2023)
Review
Medicine, Research & Experimental
Sarah H. Berth, Thomas E. Lloyd
Summary: Neurons heavily depend on axonal transport for their health due to their compartmentalization. Axonal transport is essential for delivering newly synthesized macromolecules and organelles from the cell body to the synapse (anterograde transport) and for the retrograde delivery of signaling endosomes and autophagosomes for degradation. Dysfunction in axonal transport is an early event in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, hereditary spastic paraplegia, amyotrophic lateral sclerosis, and Charcot-Marie-Tooth disease. This article provides an overview of the mechanisms regulating axonal transport, discusses their disruption in various neurodegenerative diseases, and explores therapeutic approaches targeting axonal transport.
JOURNAL OF CLINICAL INVESTIGATION
(2023)