Article
Multidisciplinary Sciences
Ali S. Shalash, Thomas W. Roesler, Ibrahim Y. Abdelrahman, Hatem S. Abulmakarem, Stefanie H. Muller, Franziska Hopfner, Gregor Kuhlenbaeumer, Gunter U. Hoeglinger, Mohamed Salama
Summary: PKAN is a rare hereditary neurodegenerative disease characterized by iron accumulation in the brain. This report describes the first genetically confirmed cases of PKAN in the Egyptian population, revealing symptoms and exome sequencing results of 4 affected siblings in a family. Studying genetics of neurodegenerative diseases in different ethnicities is crucial for understanding clinical phenotypes and disease pathomechanisms.
Article
Biochemistry & Molecular Biology
Maike Werning, Verena Dobretzberger, Martin Brenner, Ernst W. Mullner, Georg Mlynek, Kristina Djinovic-Carugo, David M. Baron, Lena Fragner, Almut T. Bischoff, Boriana Buchner, Thomas Klopstock, Wolfram Weckwerth, Ulrich Salzer
Summary: Pantothenate kinase-associated neurodegeneration (PKAN) is a progressive neurodegenerative disease caused by mutations in the pantothenate kinase 2 (PANK2) gene. Metabolic changes in erythrocytes of PKAN patients are associated with reduced cytoplasmic acetyl-CoA levels in neurons and aberrant brain iron regulation.
Article
Clinical Neurology
Lluis Planellas, Gerard Maya, Celia Painous, Pilar Santacruz, Joan Santamaria, M. J. Marti
Summary: The study describes the clinical and polysomnographic characteristics of sleep in six patients with PKAN, showing that sleep disorders are common in PKAN patients and should be considered in their management.
Article
Genetics & Heredity
Monica Alvarez-Cordoba, Marta Talaveron-Rey, Irene Villalon-Garcia, Suleva Povea-Cabello, Juan M. Suarez-Rivero, Alejandra Suarez-Carrillo, Manuel Munuera-Cabeza, Joaquin J. Salas, Jose A. Sanchez-Alcazar
Summary: Mitochondrial phosphopantetheinyl-proteins expression levels are severely reduced in PKAN cells, and treatment with pantothenate can correct the expression levels of these proteins and restore the affected pathways.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Article
Genetics & Heredity
Monica Alvarez-Cordoba, Diana Reche-Lopez, Paula Cilleros-Holgado, Marta Talaveron-Rey, Irene Villalon-Garcia, Suleva Povea-Cabello, Juan M. Suarez-Rivero, Alejandra Suarez-Carrillo, Manuel Munuera-Cabeza, Rocio Pinero-Perez, Jose A. Sanchez-Alcazar
Summary: The study examined the therapeutic effectiveness of commercial supplements in mutant PANK2 cells, finding that these supplements were able to eliminate iron accumulation, increase expression levels of key enzymes, and improve pathological alterations.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Review
Medicine, General & Internal
Meera R. Pohane, Rajshri Dafre, Nikhil G. Sontakke
Summary: This article analyzes a specific type of neurodegenerative disease, known as neurodegeneration with brain iron accumulation (NBIA), and discusses the typical and atypical manifestations of the disease as well as treatment methods. The research findings suggest that improving our understanding of PKAN and its treatment may have implications for the comprehension of other, more prevalent diseases.
CUREUS JOURNAL OF MEDICAL SCIENCE
(2023)
Review
Clinical Neurology
Nivedita Thakur, Thomas Klopstock, Suzanne Jackowski, Enej Kuscer, Fernando Tricta, Aleksandar Videnovic, Hyder A. Jinnah
Summary: PKAN is a rare neurogenetic disorder caused by genetic variants in the PANK2 gene, leading to dysfunction in pantothenate kinase activity. Recent scientific advances have enabled the design of novel therapeutic approaches for PKAN.
MOVEMENT DISORDERS
(2021)
Review
Chemistry, Medicinal
Monica Alvarez-Cordoba, Marta Talaveron-Rey, Suleva Povea-Cabello, Paula Cilleros-Holgado, David Gomez-Fernandez, Rocio Pinero-Perez, Diana Reche-Lopez, Manuel Munuera-Cabeza, Alejandra Suarez-Carrillo, Ana Romero-Gonzalez, Jose Manuel Romero-Dominguez, Alejandra Lopez-Cabrera, Jose angel Armengol, Jose Antonio Sanchez-Alcazar
Summary: Neurodegeneration with brain iron accumulation (NBIA) is a group of progressive genetic disorders characterized by the deposition of iron in specific areas of the brain. The most common subtype is pantothenate kinase-associated neurodegeneration (PKAN), for which there are currently no effective treatments. This review discusses the potential of patient-derived cell models in identifying pharmacological compounds for precision medicine in PKAN.
Article
Neurosciences
Fan Yang, Juan Wang, Ze Yang, Zhaorui Ren, Fanyi Zeng
Summary: In this study, whole-exome sequencing and functional analysis were performed to investigate the pathogenesis of PKAN in two siblings from a Chinese family. Compound heterozygous mutations of the PANK2 gene were detected, and one of the mutations was identified as a novel pathogenic variant for PKAN.
INTERNATIONAL JOURNAL OF NEUROSCIENCE
(2022)
Review
Clinical Neurology
Yilun Tao, Chen Zhao, Dong Han, Yiju Wei, Lihong Wang, Wenxia Song, Xiaoze Li
Summary: The patient is a 4-year-old with PKAN, presenting with developmental regression, progressive inability to walk, and limb tremors. Neuroimaging showed eye-of-the-tiger sign. Whole exome sequencing identified compound heterozygous mutations of c.1213T>G (p.Tyr405Asp) and c.1502T>A (p.Ile501Asn) in the PANK2 gene. A review of all known PANK2 variants observed in reported PKAN patients was conducted to improve understanding of genotype-phenotype associations in PKAN patients.
FRONTIERS IN NEUROLOGY
(2023)
Article
Clinical Neurology
Diones Rivera, Pedro Roa-Sanchez, Pamela Bido, Herwin Speckter, Jairo Oviedo, Peter Stoeter
Summary: This study found reduced global structural connectivity within the white matter and negative correlation of motor system-related tracts in PKAN patients, which is consistent with the concept of general functional disturbance of the motor system in PKAN.
PARKINSONISM & RELATED DISORDERS
(2022)
Article
Biochemistry & Molecular Biology
Camilla Ceccatelli Berti, Alexandru Ionut Gilea, Marco Armando De Gregorio, Paola Goffrini
Summary: Mutations in the PANK2 gene cause PKAN, the most common form of neurodegeneration with brain iron accumulation. A yeast model has been developed to study PKAN, revealing potential treatments and genotype/phenotype correlations. Two molecules were found to rescue multiple defects associated with PKAN deficiency.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Genetics & Heredity
Marta Talaveron-Rey, Monica Alvarez-Cordoba, Irene Villalon-Garcia, Suleva Povea-Cabello, Juan M. Suarez-Rivero, David Gomez-Fernandez, Ana Romero-Gonzalez, Alejandra Suarez-Carrillo, Manuel Munuera-Cabeza, Paula Cilleros-Holgado, Diana Reche-Lopez, Rocio Pinero-Perez, Jose A. Sanchez-Alcazar
Summary: This study evaluates the role of alpha-lipoic acid (alpha-LA) in reversing pathological alterations in fibroblasts and induced neurons derived from PKAN patients. The results indicate that alpha-LA can correct all pathological alterations in mutant fibroblasts with residual PANK2 expression, but has no effect on fibroblasts with truncated/incomplete protein expression. The positive effect of alpha-LA is also confirmed in induced neurons derived from mutant fibroblasts.
ORPHANET JOURNAL OF RARE DISEASES
(2023)
Article
Multidisciplinary Sciences
Christian C. Dibble, Samuel A. Barritt, Grace E. Perry, Evan C. Lien, Renee C. Geck, Sarah E. DuBois-Coyne, David Bartee, Thomas T. Zengeya, Emily B. Cohen, Min Yuan, Benjamin D. Hopkins, Jordan L. Meier, John G. Clohessy, John M. Asara, Lewis C. Cantley, Alex Toker
Summary: In response to hormones and growth factors, the PI3K signalling network plays a crucial role in regulating metabolism and growth by controlling cellular nutrient uptake, energy generation, cofactor production, and macromolecule biosynthesis. This study reveals that PI3K signalling stimulates the de novo synthesis of coenzyme A (CoA), a key metabolic cofactor, and identifies PANK2 and PANK4 as substrates of the PI3K effector kinase AKT. Furthermore, the study shows that PANK4 acts as a suppressor of CoA synthesis and phosphorylation by AKT relieves this suppression. Ultimately, the PI3K-PANK4 axis regulates important processes such as lipid metabolism and proliferation by controlling the abundance of acetyl-CoA and other acyl-CoAs.
Article
Oncology
Andreas Rimner, Zachary R. Moore, Stephanie Lobaugh, Alexander Geyer, Daphna Y. Gelblum, Raja-Elie E. Abdulnour, Annemarie F. Shepherd, Narek Shaverdian, Abraham J. Wu, John Cuaron, Jamie E. Chaft, Marjorie G. Zauderer, Juliana Eng, Gregory J. Riely, Charles M. Rudin, Nicholas Vander Els, Mohit Chawla, Megan McCune, Henry Li, David R. Jones, Dennis M. Sopka, Charles B. Simone, Raymond Mak, Gerald L. Weinhouse, Zhongxing Liao, Daniel R. Gomez, Zhigang Zhang, Paul K. Paik
Summary: The purpose of the study was to investigate the efficacy and safety of nintedanib added to a prednisone taper in reducing pulmonary exacerbations in patients with radiation pneumonitis. The results showed that the addition of nintedanib to the treatment had a significant effect in reducing pulmonary exacerbations in RP patients.
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2023)
Article
Clinical Neurology
Marta Correa-Vela, Joao Carvalho, Julia Ferrero-Turrion, Ana Cazurro-Gutierrez, Maria Vanegas, Victoria Gonzalez, Ramiro Alvarez, Anna Marce-Grau, Antonio Moreno, Alfons Macaya-Ruiz, Belen Perez-Duenas
Summary: This study aims to evaluate early dystonic features in children and adolescents with SGCE-myoclonus-dystonia. The study found that these patients show recognizable dystonic patterns and sensory tricks, which can lead to early diagnosis and timely treatment.
DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY
(2023)
Article
Clinical Neurology
Pavel Filip, Robert Jech, Anna Fecikova, Petra Havrankova, Filip Ruzicka, Karsten Mueller, Dusan Urgosik
Summary: The research found that GPi DBS significantly affects the brain connectivity patterns and clinical outcomes of dystonia patients, restoring both global subcortical connectivity patterns and altering local connectivity away from healthy controls.
Article
Genetics & Heredity
Anastasia Ambrose, Melissa Sheehan, Shalini Bahl, Taryn Athey, Shailly Ghai-Jain, Alicia Chan, Saadet Mercimek-Andrews
Summary: This study reports on the phenotypic and genotypic spectrum of mitochondrial long-chain fatty acid oxidation and carnitine metabolism defects, comparing treatment outcomes between symptomatic and asymptomatic patients. The study identified seven different defects and found that symptomatic patients had higher hospital admission rates and longer hospital stays.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Clinical Neurology
Alessia Nasca, Niccolo E. Mencacci, Federica Invernizzi, Michael Zech, Ignacio J. Keller Sarmiento, Andrea Legati, Chiara Frascarelli, Bernabe Bustos, Luigi M. Romito, Dimitri Krainc, Juliane Winkelmann, Miryam Carecchio, Nardo Nardocci, Giovanna Zorzi, Holger Prokisch, Steven J. Lubbe, Barbara Garavaglia, Daniele Ghezzi
Summary: Nasca et al. have discovered a new candidate gene for dystonia, ATP5F1B, which encodes a subunit of the mitochondrial ATP synthase. This gene is associated with early-onset isolated dystonia in two families with autosomal dominant inheritance and incomplete penetrance. Functional studies showed a dominant-negative effect of the identified ATP5F1B variants, leading to reduced activity of complex V and impaired mitochondrial function.
Article
Clinical Neurology
Marc Rodrigo-Gisbert, Arnau Llaurado, Andres Baucells, Cristina Auger, Victoria Gonzalez
Summary: We report a case of an 82-year-old woman with subacute altered mental status, oculomotor disturbances, and ataxia. The examination revealed bilateral ptosis, complete horizontal ophthalmoplegia, limited vertical eye movements during upgaze, and prominent truncal ataxia. MRI showed mild hyperintensity in the posterior brainstem extending to the upper cervical cord without gadolinium enhancement. This case highlights the importance of comprehensive differential diagnosis and screening for malignancy in patients with subacute brainstem encephalitis, in case of negative initial workup.
Review
Clinical Neurology
Maria Novelli, Serena Galosi, Giovanna Zorzi, Simone Martinelli, Alessandro Capuano, Francesca Nardecchia, Tiziana Granata, Luca Pollini, Martina Di Rocco, Carlo Efisio Marras, Nardo Nardocci, Vincenzo Leuzzi
Summary: To evaluate the clinical spectrum, course, and response to treatments of GNAO1 pathogenic or likely pathogenic variants, researchers analyzed the clinical phenotype, genetic data, and treatment history of 157 cases. The study found that hyperkinetic movement disorder characterized most of the patients, with severe hypotonia and disturbances of postural control in the early stages. Deep brain stimulation showed a good response in almost all patients, and milder phenotypes with late-onset dystonia and other neurological signs were also observed.
PARKINSONISM & RELATED DISORDERS
(2023)
Article
Clinical Neurology
Cathrin Lytomt Salvador, Mari Oppeboen, Anja Osteby Vassli, Helle Cecilie Viekilde Pfeiffer, Kristin Nielsen Varhaug, Katja Benedikte Presto Elgstoen, Mazyar Yazdani
Summary: This study aimed to diagnose two suspected Kearns-Sayre syndrome (KSS) patients, and found that these patients had higher levels of free sialic acid and sphingomyelin C16:0 (d18:1/C16:0) in the cerebrospinal fluid compared to four control groups (patients with mitochondrial disorders, nonmitochondrial disorders, low 5-MTHF, or increased tau proteins). The study also reported the first evidence of elevated sphingomyelin C16:0 (d18:1/C16:0) and tau protein in KSS, and suggested these biomarkers in the diagnostics of KSS.
PEDIATRIC NEUROLOGY
(2023)
Review
Clinical Neurology
Aleksandar Videnovic, Helle C. V. Pfeiffer, Anna Tylki-Szymanska, Elizabeth Berry-Kravis, Fatih Ezgu, Jitendra Ganju, Agnieszka Jurecka, Anthony E. Lang
Summary: Significant challenges exist in clinical trial development for examining treatment response in patients with rare diseases, particularly those with central nervous system involvement and heterogeneity in manifestations. Key decisions such as patient selection, endpoints, study duration, control groups, and statistical analyses greatly impact the success of the study. Strategies for successful clinical trial development in rare diseases, using pantothenate kinase-associated neurodegeneration (PKAN) as an example, can be applied to other rare diseases with movement disorders. There is an urgent need for a paradigm shift in regulatory processes to accelerate medical product development and provide early interventions for patients with rare neurodegenerative diseases.
FRONTIERS IN NEUROLOGY
(2023)
Letter
Clinical Neurology
Sara Satolli, Federica Invernizzi, Federica Rachele Danti, Chiara Reale, Celeste Panteghini, Nardo Nardocci, Barbara Garavaglia, Giovanna Zorzi
MOVEMENT DISORDERS CLINICAL PRACTICE
(2023)
Letter
Clinical Neurology
Ivana Dzinovic, Elisabeth Graf, Melanie Brugger, Riccardo Berutti, Iva Prihodova, Astrid Blaschek, Juliane Winkelmann, Robert Jech, Katharina Vill, Michael Zech
MOVEMENT DISORDERS CLINICAL PRACTICE
(2023)
Article
Clinical Neurology
Martin Srp, Tereza Bartosova, Jiri Klempir, Rebeka Lagnerova, Ota Gal, Tereza Listvanova, Robert Jech, Evzen Ruzicka, Martina Hoskovcova
Summary: The effects of expiratory muscle strength training (EMST) on patients with multiple system atrophy (MSA) were investigated in this study. After an 8-week training period, the maximal expiratory pressure (MEP) significantly increased, indicating improved expiratory muscle strength. However, the voluntary peak cough flow (vPCF) did not show significant changes. The index of pulmonary dysfunction was found to be a useful tool for detecting altered cough efficacy and decreased expiratory muscle strength in MSA patients.
MOVEMENT DISORDERS CLINICAL PRACTICE
(2023)
Review
Clinical Neurology
Laia Nou-Fontanet, Carmen Martin-Gomez, Rebeca Isabel-Gomez, Anne-Catherine Bachoud-Levi, Giovanna Zorzi, Alessandro Capuano, Juan Antonio Blasco-Amaro, Juan Dario Ortigoza-Escobar
Summary: This study aimed to provide clinical recommendations for the management of chorea in NKX2-1-RD. The available evidence suggests that methylphenidate may be effective in improving chorea symptoms, but the quality of evidence is low, and more rigorous studies are needed to provide sufficient clinical recommendations.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Editorial Material
Clinical Neurology
Andreu Vilaseca, Elena Martinez-Saez, Victoria Gonzalez, Cristina Auger, Laura Naranjo, Raquel Ruiz-Garcia
Summary: Paraneoplastic cerebellar degeneration (PCD) has been observed in a small number of patients with melanoma and specific neuronal antibodies (Yo and CARPVIII).
Editorial Material
Clinical Neurology
Marta Mercati, Federica Graziola, Laura Canafoglia, Davide Caputo, Federica Rachele Danti, Chiara Reale, Giovanna Zorzi
MOVEMENT DISORDERS CLINICAL PRACTICE
(2023)
Meeting Abstract
Clinical Neurology
N. E. Mencacci, N. Prakash, E. Gerard, L. Kinsley, B. K. Bolsterli, R. Steinfeld, C. Ellis, T. Tropea, T. Bardakjian, A. Lavillaureix, M. Ugolin, C. Thauvin-Robinet, M. Brugger, K. M. Riedhammer, T. Opladen, T. Wirth, C. Tranchant, M. Anheim, J. Chelly, B. A. Mendelsohn, S. Nandipati, A. Stembridge, H. S. Dafsari, H. Zempel, P. Herkenrath, S. Mercimek-Andrews, T. Laut, J. Necpal, R. Jech, M. Zech, G. Trieschmann, S. Berweck, O. Vanakker, D. Gill, F. Gardiner, S. Mohammad, H. Mefford, I. Scheffer, G. Carvill, D. Krainc
MOVEMENT DISORDERS
(2022)