Article
Neurosciences
John W. McLean, Julie A. Wilson, Tina Tian, Jennifer A. Watson, Mary VanHart, Andrew J. Bean, Steven S. Scherer, David K. Crossman, Eroboghene Ubogu, Scott M. Wilson
Summary: Endosomal sorting is crucial for neural development by regulating membrane receptor distribution and signaling pathways. Inactivation of the HGS protein in Schwann cells leads to peripheral neuropathy with deficits in motor and sensory functions, delayed myelination, and altered gene expression related to Schwann cell maturation. This study suggests that HGS is essential for endosomal sorting of ERBB2/3 receptors during Schwann cell development, implicating endosomal dysfunction in inherited peripheral neuropathies.
JOURNAL OF NEUROSCIENCE
(2022)
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
Xiaohui Duan, Yan Ma, Dongsheng Fan, Xiaoxuan Liu
Summary: In this study, 12 SH3TC2 variants (eight novel) were identified in seven families of Chinese CMT patients, with a calculated CMT4C frequency of 4.24%. The onset age and symptom presentation varied among the eight patients. The detection of variant R954* in the Chinese cohort suggests a potentially low frequency presence among Asians.
FRONTIERS IN NEUROLOGY
(2021)
Article
Clinical Neurology
Paulo Jose Lorenzoni, Claudia Suemi Kamoi Kay, Renata Dal-Pra Ducci, Otto Jesus Hernandez Fustes, Lineu Cesar Werneck, Rosana Herminia Scola
Summary: This report describes a patient with CMT4C who developed myasthenia gravis, suggesting the need for further research to confirm whether genetic neuropathies may predispose to MG.
NEUROLOGICAL SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Ryan J. Mulligan, Bettina Winckler
Summary: Intracellular endosomal trafficking plays a crucial role in maintaining protein balance and cellular signaling pathways. Small GTPases, including Rab proteins, control the coordination of this trafficking. Rab7 is particularly important in regulating endosomal maturation and functions. Mutations in Rab7 cause Charcot-Marie-Tooth 2B disease, leading to peripheral neuropathy. This review focuses on the physiological interactions and control of Rab7 effectors in neurons, emphasizing the challenges of spatiotemporal regulation in neuronal processes. The impact of Rab7 mutations on effector interactions and balance in CMT2B models is also discussed.
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
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)
Article
Clinical Neurology
Menelaos Pipis, Andrea Cortese, James M. Polke, Roy Poh, Jana Vandrovcova, Matilde Laura, Mariola Skorupinska, Arnaud Jacquier, Raul Juntas-Morales, Philippe Latour, Philippe Petiot, Guilhem Sole, Yves Fromes, Sachit Shah, Julian Blake, Byung-Ok Choi, Ki Wha Chung, Tanya Stojkovic, Alexander M. Rossor, Mary M. Reilly
Summary: This study reveals the unique phenotype of CMT2CC, which is more similar to spinal muscular atrophy than classic CMT. The disease progresses rapidly, requiring wheelchair use at an early stage and exhibiting early ankle plantarflexion weakness in a significant portion of patients.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
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
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
Clinical Neurology
Bo Sun, Zheng-Qing He, Yan-Ran Li, Jiong-Ming Bai, Hao-Ran Wang, Hong-Fen Wang, Fang Cui, Fei Yang, Xu-Sheng Huang
Summary: This study identified CMT4C as a common type of CMT4/AR CMT1 caused by SH3TC2 mutations. Three novel SH3TC2 mutations were found, highlighting the importance of a comprehensive approach including clinical assessment, nerve conduction studies, genetic analysis, and bioinformatics analysis in suspected CMT patients.
ACTA NEUROLOGICA BELGICA
(2022)
Article
Neurosciences
Mariapaola Sidoli, Chelsey B. Reed, Cristina Scapin, Pablo Paez, Douglas R. Cavener, Randal J. Kaufman, Maurizio D'Antonio, M. Laura Feltri, Lawrence Wrabetz
Summary: Despite the interaction between Perk and calcineurin in P0S63del nerves, Perk deletion paradoxically improved S63del myelin defects. Additionally, genetic manipulation of calcineurin subunits showed context-dependent protective or toxic effects in S63del, suggesting high sensitivity of Schwann cells to alterations in calcineurin activity.
JOURNAL OF NEUROSCIENCE
(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
Biochemistry & Molecular Biology
T. Reid Alderson, Elias Adriaenssens, Bob Asselbergh, Iva Pritisanac, Jonas Van Lent, Heidi Y. Gastall, Marielle A. Walti, John M. Louis, Vincent Timmerman, Andrew J. Baldwin, Justin LP Benesch
Summary: The P182L mutation in HSP27 disrupts chaperone activity and increases oligomer size, potentially impacting protein-protein interactions. This mutation weakens the binding affinity of the IxI/V motif for the core domain of HSP27, leading to altered interactions with other IxI/V-containing proteins.
Article
Neurosciences
Mahima Kapoor, Mary M. Reilly, Hadi Manji, Michael P. Lunn, S. Carr Aisling
Summary: High-dose IVIg has been proven to be safe and effective in restoring strength and ability to participate in daily activities for patients with CIDP and MMNCB. Individualized assessment plays a crucial role in improving treatment outcomes.
INTERNATIONAL JOURNAL OF NEUROSCIENCE
(2022)
Article
Clinical Neurology
Alex Y. Doets, Christa Walgaard, Hester F. Lingsma, Badrul Islam, Nowshin Papri, Yuko Yamagishi, Susumu Kusunoki, Mazen M. Dimachkie, Waqar Waheed, Noah Kolb, Kenneth C. Gorson, Bart C. Jacobs
Summary: This study validated the Erasmus Guillain-Barre Syndrome Respiratory Insufficiency Score in an international cohort and developed a more accurate region-specific model for patients from Europe/North America.
ANNALS OF NEUROLOGY
(2022)
Article
Clinical Neurology
Samuel Arends, Judith Drenthen, Peter van den Bergh, Hessel Franssen, Robert D. M. Hadden, Badrul Islam, Satoshi Kuwabara, Ricardo C. Reisin, Nortina Shahrizaila, Hiroshi Amino, Giovanni Antonini, Shahram Attarian, Claudia Balducci, Fabio Barroso, Tulio Bertorini, Davide Binda, Thomas H. Brannagan, Jan Buermann, Carlos Casasnovas, Guido Cavaletti, Chi-Chao Chao, Mazen M. Dimachkie, Ernesto A. Fulgenzi, Giuliana Galassi, Gerardo Gutierrez Gutierrez, Thomas Harbo, Hans-Peter Hartung, Sung-Tsang Hsieh, Lynette Kiers, Helmar C. Lehmann, Fiore Manganelli, Girolama A. Marfia, Giorgia Mataluni, Julio Pardo, Yann Pereon, Yusuf A. Rajabally, Lucio Santoro, Yukari Sekiguchi, Beth Stein, Mark Stettner, Antonino Uncini, Christine Verboon, Camiel Verhamme, Michal Vytopil, Waqar Waheed, Min Wang, Sasha Zivkovic, Bart C. Jacobs, David R. Cornblath
Summary: This study investigated the heterogeneity of electrodiagnostic (EDx) studies in Guillain-Barre syndrome (GBS) patients collected as part of the International GBS Outcome Study (IGOS). The results showed extensive variation in the clinical practice of EDx among IGOS centers across different regions. This diversity is likely to be present in other neuromuscular disorders and centers, emphasizing the need for standardization of EDx in future multinational GBS studies.
CLINICAL NEUROPHYSIOLOGY
(2022)
Article
Clinical Neurology
Alex Y. Doets, Hester F. Lingsma, Christa Walgaard, Badrul Islam, Nowshin Papri, Amy Davidson, Yuko Yamagishi, Susumu Kusunoki, Mazen M. Dimachkie, Waqar Waheed, Noah Kolb, Zhahirul Islam, Quazi Deen Mohammad, Thomas Harbo, Soren H. Sindrup, Govindsinh Chavada, Hugh J. Willison, Carlos Casasnovas, Kathleen Bateman, James A. L. Miller, Bianca van den Berg, Christine Verboon, Joyce Roodbol, Sonja E. Leonhard, Luana Benedetti, Satoshi Kuwabara, Peter Van den Bergh, Soledad Monges, Girolama A. Marfia, Nortina Shahrizaila, Giuliana Galassi, Yann Pereon, Jan Burmann, Krista Kuitwaard, Ruud P. Kleyweg, Cintia Marchesoni, Maria J. Sedano Tous, Luis Querol, Isabel Illa, Yuzhong Wang, Eduardo Nobile-Orazio, Simon Rinaldi, Angelo Schenone, Julio Pardo, Frederique H. Vermeij, Helmar C. Lehmann, Volkan Granit, Guido Cavaletti, Gerardo Gutierrez-Gutierrez, Fabio A. Barroso, Leo H. Visser, Hans D. Katzberg, Efthimios Dardiotis, Shahram Attarian, Anneke J. van der Kooi, Filip Eftimov, Paul W. Wirtz, Johnny P. A. Samijn, H. Jacobus Gilhuis, Robert D. M. Hadden, James K. L. Holt, Kazim A. Sheikh, Summer Karafiath, Michal Vytopil, Giovanni Antonini, Thomas E. Feasby, Catharina G. Faber, Cees J. Gijsbers, Mark Busby, Rhys C. Roberts, Nicholas J. Silvestri, Raffaella Fazio, Gert W. van Dijk, Marcel P. J. Garssen, Chiara S. M. Straathof, Kenneth C. Gorson, Bart C. Jacobs
Summary: The study validated the modified Erasmus GBS Outcome Score (mEGOS) for predicting walking ability in Guillain-Barre syndrome (GBS) patients internationally, and developed a region-specific version for patients in Europe and North America. The results showed that severe limb weakness and older age were the main predictors of poor outcomes.
Article
Clinical Neurology
Carolyn Young, John Ealing, Christopher McDermott, Tim Williams, Ammar Al-Chalabi, Tahir Majeed, Rhys Roberts, Roger Mills, Alan Tennant
Summary: The study found that dyspnea in ALS patients influences quality of life and depression largely through indirect effects, primarily via anxiety and fatigue, while disability plays a dominant role in the model.
AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
(2022)
Letter
Clinical Neurology
Christopher J. Record, Menelaos Pipis, Julian Blake, Riccardo Curro, Michael P. Lunn, Alexander M. Rossor, Matilde Laura, Andrea Cortese, Mary M. Reilly
JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM
(2022)
Article
Clinical Neurology
Mahima Kapoor, Aisling Carr, Martha Foiani, Amanda Heslegrave, Henrik Zetterberg, Andrea Malaspina, Laura Compton, Elspeth Hutton, Alexander Rossor, Mary M. Reilly, Michael P. Lunn
Summary: This study found an association between plasma neurofilament light chain (pNfL) concentration and disease activity in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), suggesting that pNfL concentration may be a useful biomarker for assessing disease remission and relapse.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Clinical Neurology
Christopher J. Record, Rana Alnasser Alsukhni, Riccardo Curro, Diego Kaski, John S. Rubin, Huw R. Morris, Andrea Cortese, Valeria Iodice, Mary M. Reilly
Summary: Biallelic repeat expansions in RFC1 have been found to cause CANVAS, a syndrome characterized by cerebellar ataxia, neuropathy, and vestibular areflexia. Additional features observed in some cases include Parkinsonism and MSA-like syndrome. We reported a case of CANVAS with severe autonomic involvement similar to classical MSA, suggesting a potential link between the two conditions.
JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM
(2022)
Article
Clinical Neurology
Sonja E. Leonhard, Annemiek A. van der Eijk, Henning Andersen, Giovanni Antonini, Samuel Arends, Shahram Attarian, Fabio A. Barroso, Kathleen J. Bateman, Manou R. Batstra, Luana Benedetti, Bianca van den Berg, Peter Van den Bergh, Jan Burmann, Mark Busby, Carlos Casasnovas, David R. Cornblath, Amy Davidson, Alex Y. Doets, Pieter A. van Doorn, Charlotte Dornonville de la Cour, Thomas E. Feasby, Janev Fehmi, Tania Garcia-Sobrino, Jonathan M. Goldstein, Kenneth C. Gorson, Volkan Granit, Robert D. M. Hadden, Thomas Harbo, Hans-Peter Hartung, Imran Hasan, Jakob Holbech, James K. L. Holt, Israt Jahan, Zhahirul Islam, Summer Karafiath, Hans D. Katzberg, Ruud P. Kleyweg, Noah Kolb, Krista Kuitwaard, Motoi Kuwahara, Susumu Kusunoki, Linda W. G. Luijten, Satoshi Kuwabara, Edward Lee Pan, Helmar C. Lehmann, Marijke Maas, Lorena Martin-Aguilar, James Al Miller, Quazi Deen Mohammad, Soledad Monges, Velina Nedkova-Hristova, Eduardo Nobile-Orazio, Julio Pardo, Yann Pereon, Luis Querol, Ricardo Reisin, Wouter Van Rijs, Simon Rinaldi, Rhys C. Roberts, Joyce Roodbol, Nortina Shahrizaila, Soren Hein Sindrup, Beth Stein, Tan Cheng-Yin, Hatice Tankisi, Anne P. Tio-Gillen, Maria J. Sedano Tous, Christine Verboon, Frederique H. Vermeij, Leo H. Visser, Ruth Huizinga, Hugh J. Willison, Bart C. Jacobs
Summary: This study analyzed the role of infections in Guillain-Barre syndrome (GBS) and their association with clinical features and disease severity. The distribution of infections varied across geographical regions, but the association between infection and clinical phenotype differed. Coinfections were common, highlighting the importance of broad serologic testing. Infections were also found to have prognostic value for GBS outcome.
Article
Clinical Neurology
Virgilio Kmetzsch, Morwena Latouche, Dario Saracino, Daisy Rinaldi, Agnes Camuzat, Thomas Gareau, Isabelle Le Ber, Olivier Colliot, Emmanuelle Becker
Summary: The study found that most of the selected microRNAs showed significant differences in expression in the C9orf72 cohort, while only a small proportion of microRNAs showed differential expression in the GRN cohort. Multivariate analysis showed that only individuals in the C9orf72 cohort could be adequately classified, with some of the signatures showing high accuracy in distinguishing controls from presymptomatic subjects and patients. This suggests that previously identified microRNAs may serve as potential biomarkers for C9orf72-associated disease, but may not be as useful for GRN-associated disease.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2022)
Letter
Clinical Neurology
Christopher J. Record, Menelaos Pipis, Roy Poh, James M. Polke, Mary M. Reilly
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Article
Clinical Neurology
Helle Al-Hakem, Alex Y. Doets, Amro Maher Stino, Sasha A. Zivkovic, Henning Andersen, Hugh J. Willison, David R. Cornblath, Kenneth C. Gorson, Zhahirul Islam, Quazi Deen Mohammad, Soren Hein Sindrup, Susumu Kusunoki, Amy Davidson, Carlos Casasnovas, Kathleen Bateman, James A. L. Miller, Bianca van den Berg, Christine Verboon, Joyce Roodbol, Sonja E. Leonhard, Samuel Arends, Linda W. G. Luijten, Luana Benedetti, Satoshi Kuwabara, Peter van den Bergh, Soledad Monges, Girolama A. Marfia, Nortina Shahrizaila, Giuliana Galassi, Yann Pereon, Jan Burmann, Krista Kuitwaard, Ruud P. Kleyweg, Cintia Marchesoni, Maria J. Sedano Tous, Luis Querol, Lorena Martin-Aguilar, Yuzhong Wang, Eduardo Nobile-Orazio, Simon Rinaldi, Angelo Schenone, Julio Pardo, Frederique H. Vermeij, Waqar Waheed, Helmar C. Lehmann, Volkan Granit, Beth Stein, Guido Cavaletti, Gerardo Gutierrez-Gutierrez, Fabio A. Barroso, Leo H. Visser, Hans D. Katzberg, Efthimios Dardiotis, Shahram Attarian, Anneke J. van der Kooi, Filip Eftimov, Paul W. Wirtz, Johnny P. A. Samijn, H. Jacobus Gilhuis, Robert D. M. Hadden, James K. L. Holt, Kazim A. Sheikh, Noah Kolb, Summer Karafiath, Michal Vytopil, Giovanni Antonini, Thomas E. Feasby, Catharina Faber, Hans Kramers, Mark Busby, Rhys C. Roberts, Nicholas J. Silvestri, Raffaella Fazio, Gert W. van Dijk, Marcel P. J. Garssen, Jan Verschuuren, Thomas Harbo, Bart C. Jacobs, IGOS Consortium
Summary: Based on 1,500 patients in the International GBS Outcome Study, this study investigated the relationship between CSF findings and clinical and electrodiagnostic subtypes, severity, and outcome of Guillain-Barre syndrome (GBS). The results showed that most patients had albuminocytologic dissociation (ACD) in their CSF, and high protein levels were associated with early severe disease course and demyelinating subtype of GBS.
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)
Review
Clinical Neurology
Caroline Kramarz, Elaine Murphy, Mary M. Reilly, Alexander M. Rossor
Summary: Nutritional peripheral neuropathies are a global issue influenced by geopolitical, cultural, and socioeconomic factors. B-vitamin deficiencies, particularly in vitamins B-1, B-2, B-6, B-9, and B-12, are the most common cause of peripheral neuropathy. This review discusses the historical and current understanding of these deficiencies, as well as diagnostic tools and genetic diseases related to B-vitamin metabolism. Endemic outbreaks of peripheral neuropathy in the past centuries further emphasize the importance of identifying and preventing nutritional deficiencies to reduce disability.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Article
Multidisciplinary Sciences
Daniel M. Williams, Hailey R. Hornsby, Ola M. Shehata, Rebecca Brown, Marta Gallis, Naomi Meardon, Thomas A. H. Newman, Megan Plowright, Domen Zafred, Amber S. M. Shun-Shion, Anthony J. Hodder, Deepa Bliss, Andrew Metcalfe, James R. Edgar, David E. Gordon, Jon R. Sayers, Martin J. Nicklin, Miles Carroll, Pitch Pitch Consortium, Paul J. Collini, Stephen Brown, Thushan I. De Silva, Andrew A. Peden
Summary: This study explored the serological responses against SARS-CoV-2 proteins other than N and S, finding that a high percentage of infected individuals developed detectable IgG against the M protein. Compared to N antibodies, M IgG had a slower decay and greater specificity. Combining N and M IgG detection increased the sensitivity for SARS-CoV-2 seroprevalence. These findings suggest that screening for M seroconversion could be an effective method for detecting vaccine breakthrough infections, using high-content microscopy to identify immunogenic targets.