Article
Clinical Neurology
Marina Frasquet, Ricard Rojas-Garcia, Herminia Argente-Escrig, Juan Francisco Vazquez-Costa, Nuria Muelas, Juan Jesus Vilchez, Rafael Sivera, Elvira Millet, Marisa Barreiro, Jordi Diaz-Manera, Janina Turon-Sans, Elena Cortes-Vicente, Luis Querol, Laura Ramirez-Jimenez, Dolores Martinez-Rubio, Ana Sanchez-Monteagudo, Carmen Espinos, Teresa Sevilla, Vincenzo Lupo
Summary: This study confirms the genetic heterogeneity of distal hereditary motor neuropathies and establishes biallelic SORD mutations as a cause of the disease in different populations. The study also reveals the genetic diagnostic rate, most common genetic mutations, and prevalence of the disease.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Article
Clinical Neurology
Yi-Chu Liao, Fu-Pang Chang, Han-Wei Huang, Ting-Bing Chen, Ying-Tsen Chou, Shao-Lun Hsu, Kang-Yang Jih, Yi-Hong Liu, Cheng-Tsung Hsiao, Hiromi Fukukda, Takeshi Mizuguchi, Kon-Ping Lin, Chou-Ching K. Lin, Naomichi Matsumoto, Marina Kennerson, Yi-Chung Lee
Summary: This study identifies the GGC repeat expansion in the NOTCH2NLC gene as an important cause of inherited neuropathy. Among the patients with Charcot-Marie-Tooth disease, 10.6% of those with axonal CMT have the GGC repeat expansion. The expansion leads to sensory predominant neuropathy with an average disease onset age of 37.1 years.
Article
Clinical Neurology
Zhongbo Chen, Reza Maroofian, A. Nazli Basak, Leena Shingavi, Mert Karakaya, Stephanie Efthymiou, Emil K. Gustavsson, Leyla Meier, Kiran Polavarapu, Seena Vengalil, Veeramani Preethish-Kumar, Bevinahalli N. Nandeesh, Nalan Gokce Gunes, Onur Akan, Fatma Candan, Bertold Schrank, Stephan Zuchner, David Murphy, Mahima Kapoor, Mina Ryten, Brunhilde Wirth, Mary M. Reilly, Atchayaram Nalini, Henry Houlden, Payam Sarraf
Summary: Pathogenic variants in PLEKHG5 have been reported in patients with autosomal recessive intermediate Charcot-Marie-Tooth disease and spinal muscular atrophy. The study identified novel biallelic variants in PLEKHG5 in 13 individuals from nine families, showing variable disease severity and age of onset. The findings suggest PLEKHG5-associated neuropathies as an important differential diagnosis in non-5q spinal muscular atrophy cases, expanding the understanding of the disease spectrum.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Review
Clinical Neurology
Marina Frasquet, Teresa Sevilla
Summary: Despite the widespread use of new-generation sequencing (NGS) and the identification of new genes, only one third of dHMN patients receive a molecular diagnosis. International collaboration between researchers has led to the discovery of new genes, such as SORD and VWA1, which are implicated in dHMN cases.Mutation in SORD is the most common cause of autosomal recessive forms of dHMN.
CURRENT OPINION IN NEUROLOGY
(2022)
Article
Clinical Neurology
Arnaud Jacquier, Julian Theuriet, Fanny Fontaine, Valentine Mosbach, Nicolas Lacoste, Shams Ribault, Valerie Risson, Julien Carras, Laurent Coudert, Thomas Simonet, Philippe Latour, Tanya Stojkovic, Juliette Piard, Anne Cosson, Gaetan Lesca, Francoise Bouhour, Stephane Allouche, Helene Puccio, Antoine Pegat, Laurent Schaeffer
Summary: Jacquier et al. identified a homozygous variant in the COQ7 gene in a family with distal hereditary motor neuropathy. This variant leads to a decrease in coenzyme Q10 production, causing impaired mitochondrial metabolism. Coenzyme Q10 supplementation may serve as a potential treatment for this disorder.
Review
Neurosciences
Pedro A. Lazo, Patricia Morejon-Garcia
Summary: Distal hereditary neuropathies and neuro motor diseases are complex neurological phenotypes associated with pathogenic variants in a large number of genes, but in some the origin is unknown. Recently, rare pathogenic variants of the human VRK1 gene have been associated with these neurological phenotypes. All VRK1 pathogenic variants are recessive, and their clinical presentation occurs in either homozygous or compound heterozygous patients. The underlying common pathogenic mechanism is a likely consequence of the roles that the VRK1 protein plays in the regulation on the stability and assembly of Cajal bodies, which affect RNA maturation and processing, neuronal migration of RNPs along axons, and DNA-damage responses. The clinical heterogeneity of the neurological phenotypes associated with VRK1 is a likely consequence of the protein complexes in which VRK1 is integrated, which include several proteins known to be associated with Cajal bodies and DNA damage responses.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Clinical Neurology
Carlos Pablo de Fuenmayor-Fernandez de la Hoz, Vincenzo Lupo, Laura Bermejo-Guerrero, Paloma Martin-Jimenez, Aurelio Hernandez-Lain, Montse Olive, Eduard Gallardo, Jesus Esteban-Perez, Carmen Espinos, Cristina Dominguez-Gonzalez
Summary: This study describes a new phenotype associated with a novel variant in BAG3 gene, presenting as autosomal dominant adult-onset distal hereditary motor neuronopathy. The findings expand the phenotypic spectrum of BAG3-related disorders and highlight the importance of considering BAG3 gene variants in the differential diagnosis of distal hereditary motor neuronopathies.
JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Adriana P. Rebelo, Pedro J. Tomaselli, Jessica Medina, Ying Wang, Maike F. Dohrn, Eva Nyvltova, Matt C. Danzi, Mark Garrett, Sean E. Smith, Alan Pestronk, Chengcheng Li, Ariel Ruiz, Elizabeth Jacobs, Shawna M. E. Feely, Marcondes C. Franca Jr, Marcus Gomes, Diogo F. Santos, Surinder Kumar, David B. Lombard, Mario Saporta, Siegfried Hekimi, Antoni Barrientos, Conrad Weihl, Michael E. Shy, Wilson Marques, Stephan Zuchner
Summary: Rebelo et al. identified COQ7 biallelic variants in nine families with distal hereditary motor neuropathy with upper motor neuron involvement, expanding the clinical phenotype of this gene. COQ7 mutations have been previously associated with primary CoQ(10) deficiency, and our findings indicate a molecular pathway involving CoQ(10) biosynthesis deficiency and mitochondrial dysfunction in patients with distal hereditary motor neuropathy. Fibroblasts from patients showed protein instability, reduced CoQ(10) levels, and abnormal accumulation of the biosynthetic precursor DMQ(10). Further studies are needed to evaluate the potential benefits of CoQ(10) supplementation in the clinical outcome of the disease.
Article
Clinical Neurology
Anthony N. Cutrupi, Ramesh K. Narayanan, Gonzalo Perez-Siles, Bianca R. Grosz, Kaitao Lai, Alexandra Boyling, Melina Ellis, Ruby C. Y. Lin, Brent Neumann, Di Mao, Motonari Uesugi, Garth A. Nicholson, Steve Vucic, Mario A. Saporta, Marina L. Kennerson
Summary: This study identifies a novel gene-intergenic fusion transcript (UBE3C-IF) associated with distal hereditary motor neuropathy 1 (DHMN1). The UBE3C-IF transcript leads to decreased UBE3C protein levels in DHMN1 patient-derived motor neurons and causes synaptic transmission deficits and susceptibility to heat stress in a Caenorhabditis elegans model.
Article
Engineering, Biomedical
Bente E. Bloks, Lise M. Wilders, Jan Willem K. Louwerens, Alexander C. Geurts, Jorik Nonnekes, Noel L. W. Keijsers
Summary: This study aimed to understand the plantar pressure situation of patients with hereditary motor and sensory neuropathies (HMSN) and propose a quantitative outcome measure for the evaluation of surgical interventions. Plantar pressure measurements of 52 HMSN patients and 586 healthy controls were evaluated, revealing differences in plantar pressure patterns among different foot deformity categories. It was suggested to use root mean square deviations (RMSD) in combination with the fifth metatarsal head pressure ratio as outcome measures for evaluating surgical interventions in HMSN patients.
JOURNAL OF NEUROENGINEERING AND REHABILITATION
(2023)
Article
Clinical Neurology
G. McMacken, R. G. Whittaker, R. Charlton, R. Barresi, H. Lochmuller, R. Horvath
Summary: This study aimed to characterize the clinical, neurophysiological, and genetic features of patients with upper limb predominant Charcot-Marie-Tooth disease (CMT), identifying an overlapping phenotype of neuropathy and myopathy in some cases. The majority of these patients could not be genetically diagnosed by gene panel testing, suggesting further genetic heterogeneity.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Article
Clinical Neurology
Diana Esteller, Jasper Morrow, Jorge Alonso-Perez, David Reyes, Alvaro Carbayo, Giulia Bisogni, Michela Cateruccia, Mauro Monforte, Giorgio Tasca, Aljwhara Alangary, Chiara Marini-Bettolo, Mario Sabatelli, Matilde Laura, Gita Ramdharry, Carla Bolano-Diaz, Janina Turon-Sans, Ana Topf, Michella Guglieri, Alexander M. Rossor, Montse Olive, Enrico Bertini, Volker Straub, Mary M. Reilly, Ricard Rojas-Garcia, Jordi Diaz-Manera
Summary: Distal motor neuropathies (dHMN) are a group of heterogeneous diseases characterized by progressive muscle weakness in the distal muscles of the lower and upper limbs. This study aimed to investigate the imaging features and patterns of muscle involvement in dHMN patients using muscle magnetic resonance imaging (MRI). The findings provide valuable information for the diagnosis of dHMN.
NEUROMUSCULAR DISORDERS
(2023)
Review
Clinical Neurology
Josef Finsterer, Wolfgang N. Loescher, Julia Wanschitz, Stefan Iglseder
Summary: Orphan neuropathies, with a prevalence <1:200000 in the US and <5:10000 in Europe, constitute the majority of neuropathies, including both acquired and hereditary forms. These conditions are complex in etiology, diagnosis, and treatment, posing challenges in understanding and managing them effectively.
JOURNAL OF NEUROMUSCULAR DISEASES
(2021)
Article
Genetics & Heredity
Si On Lim, Na Young Jung, Ah Jin Lee, Hee Ji Choi, Hye Mi Kwon, Wonseok Son, Soo Hyun Nam, Byung-Ok Choi, Ki Wha Chung
Summary: This study identified pathogenic or likely pathogenic variants in several sHSP genes associated with inherited peripheral neuropathies in Korean IPN families. Most variants were located in the evolutionally conserved alpha-crystallin domain. The findings can contribute to the molecular diagnosis and care of patients with CMT2 and dHMN.
Article
Clinical Neurology
Grace McMacken, Roger G. Whittaker, Ruth Wake, Hanns Lochmuller, Rita Horvath
Summary: This study identifies inherited defects of the neuromuscular junction (NMJ) as a diverse range of diseases, including peripheral neuropathies and congenital myasthenic syndromes (CMS). The beta-2 adrenergic receptor agonist salbutamol has been shown to improve structural defects at the NMJ in CMS patients, but does not significantly improve motor function. These findings highlight the importance of the NMJ in various motor neuropathies and suggest it as a potential therapeutic target.
JOURNAL OF NEUROLOGY
(2023)
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
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
Doaa M. Taha, Benjamin E. Clarke, Claire E. Hall, Giulia E. Tyzack, Oliver J. Ziff, Linda Greensmith, Bernadett Kalmar, Mhoriam Ahmed, Aftab Alam, Eric P. Thelin, Nuria Marco Garcia, Adel Helmy, Christopher R. Sibley, Rickie Patani
Summary: This study investigates the cellular autonomy and uniformity of astrocyte reactive transformation in different genetic forms of amyotrophic lateral sclerosis. By using enriched and human induced pluripotent stem cell-derived astrocytes from patients with VCP and SOD1 mutations, the study shows that reactive transformation can occur cell-autonomously in ALS astrocytes and there is molecular and functional heterogeneity between different disease-causing mutations.
Article
Clinical Neurology
Alexander Martin Rossor, Mahima Kapoor, Henny Wellington, Emily Spaulding, James N. Sleigh, Robert W. Burgess, Matilde Laura, Henrik Zetterberg, Alexa Bacha, Xingyao Wu, Amanda Heslegrave, Michael E. Shy, Mary M. Reilly
Summary: The study evaluated plasma neurofilament light chain (NFL) as a disease biomarker in CMT, showing increased NFL concentrations in some CMT patients but decreased in others. For patients with CMT1A, the small difference in NFL concentrations compared to healthy controls and lack of significant change over time suggest that plasma NFL may not have sufficient sensitivity to detect clinically meaningful treatment responses in adulthood.
JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM
(2022)
Article
Clinical Neurology
Mahima Kapoor, Laura Compton, Alex Rossor, Elsbeth Hutton, Hadi Manji, Mike Lunn, Mary Reilly, Aisling Carr
Summary: Regular immunoglobulin treatment is crucial for maintaining strength and preventing disability in chronic inflammatory demyelinating polyneuropathy (CIDP). Differentiating between active disease and remission in CIDP patients is essential for treatment decisions and clinical trial design. A study comparing treatment cessation and gradual dose reduction in stable CIDP patients found that while cessation led to faster disease deterioration, all patients were able to return to their previous baseline and some achieved remission for over 2 years. This study suggests that a treatment cessation trial with close clinical monitoring is an efficient, cost-effective, and safe approach to assessing disease activity in CIDP.
JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM
(2021)
Review
Clinical Neurology
Alexander M. Rossor, Mary M. Reilly
Summary: This article reviews the most common cause of neurogenic arthrogryposis, SMALED, and discusses how the clinical and radiological phenotype has helped identify the genetic cause of SMALED2. The similarities and differences between human SMALED phenotype and mouse models are also reviewed, providing insights into potential mechanisms of motor neuron loss in these disorders.
NEUROMUSCULAR DISORDERS
(2021)
Review
Clinical Neurology
Alexander M. Rossor, Mary M. Reilly
Summary: This article reviews the blood biomarkers of disease activity for common subtypes of peripheral neuropathy, including inflammatory demyelinating neuropathies, vasculitic neuropathy, diabetic neuropathy, chemotherapy-induced neuropathy, and Charcot-Marie-Tooth disease. Measurement of serum proteins, particularly neuron-specific proteins and cell-specific proteins, can assess the disease activity level of neuropathy.
ACTA NEUROLOGICA SCANDINAVICA
(2022)
Article
Clinical Neurology
Caroline Kramarz, Alexander M. Rossor
Summary: This update reviews the recent discovery of autosomal recessive variants in sorbitol dehydrogenase and therapeutic advances in hereditary neuropathy, which provide new insights and methods for the treatment of diseases such as hereditary motor neuropathy and CMT2.
JOURNAL OF NEUROLOGY
(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)
Letter
Clinical Neurology
Christopher J. Record, Menelaos Pipis, Roy Poh, James M. Polke, Mary M. Reilly
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(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)
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)