Review
Biochemistry & Molecular Biology
Arun Meyyazhagan, Antonio Orlacchio
Summary: This review provides an overview of hereditary spastic paraplegia (HSP), including its clinical manifestations, etiology, diagnosis, and treatment methods. Although modern medical interventions have helped, there is still room for improvement in the treatment of this disorder.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Neurosciences
Emanuele Panza, Arun Meyyazhagan, Antonio Orlacchio
Summary: Hereditary Spastic Paraplegias (HSPs) are a group of heterogeneous diseases characterized by progressive spasticity and weakness of the lower limbs. Although HSPs are rare conditions, they pose significant health and economic challenges. The molecular diagnostic rate for HSPs is variable, suggesting the involvement of more genes and the need for different diagnostic approaches. HSPs exhibit genetic heterogeneity, allelic heterogeneity, and overlap with other neurological conditions.
EXPERIMENTAL NEUROLOGY
(2022)
Article
Neurosciences
Qiao Wei, Hao Yu, Pei-Shan Wang, Juan-Juan Xie, Hai-Lin Dong, Zhi-Ying Wu, Hong-Fu Li
Summary: This study identified five different COQ4 variants in three Chinese HSP pedigrees, expanding the phenotypic spectrum of COQ4-related disorders. Additionally, two early-onset pure HSP cases caused by COQ4 variants were described for the first time.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Clinical Neurology
Francesca Sardina, Davide Valente, Gaia Fattorini, Ettore Cioffi, Gianmarco Dalla Zanna, Alessandra Tessa, Daniela Trisciuoglio, Silvia Soddu, Filippo M. Santorelli, Carlo Casali, Cinzia Rinaldo
Summary: The study developed an automated, simple, fast, and non-invasive cell imaging-based method to quantify microtubule cytoskeleton organization changes in lymphoblastoid cells and peripheral blood mononuclear cells. The results showed that individuals affected by SPG4-hereditary spastic paraplegia have a polarized microtubule cytoskeleton organization. The method was able to discriminate SPG4-hereditary spastic paraplegia from healthy donors and other subtypes, and detect the effects of spastin protein level changes.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Siddharth Srivastava, Hagar Mor Shaked, Kenneth Gable, Sita D. Gupta, Xueyang Pan, Niranjanakumari Somashekarappa, Gongshe Han, Payam Mohassel, Marc Gotkine, Elizabeth Doney, Paula Goldenberg, Queenie K. G. Tan, Yi Gong, Benjamin Kleinstiver, Brian Wishart, Heidi Cope, Claudia Brito Pires, Hannah Stutzman, Rebecca C. Spillmann, Reza Sadjadi, Orly Elpeleg, Chia-Hsueh Lee, Hugo J. Bellen, Simon Edvardson, Florian Eichler, Teresa M. Dunn
Summary: Sphingolipids, abundant in myelin membranes, are crucial for the structural and signalling functions in the mammalian nervous system. Serine palmitoyltransferase (SPTSSA) is the enzyme responsible for the rate-limiting reaction in sphingolipid synthesis and its activity is tightly regulated by ORMDL proteins. Excessive sphingolipid synthesis due to impaired homeostatic regulation of serine palmitoyltransferase was found to be responsible for defects in early brain development and function. SRivastava et al. identified SPTSSA variants that disrupt ORMDL-mediated regulation of SPT, leading to hereditary spastic paraplegia.
Article
Clinical Neurology
Azusa Ikeda, Tatsuro Kumaki, Yu Tsuyusaki, Megumi Tsuji, Yumi Enomoto, Atsushi Fujita, Hirotomo Saitsu, Naomichi Matsumoto, Kenji Kurosawa, Tomohide Goto
Summary: This study retrospectively evaluated the genetic analyses, family history, clinical courses, MRI findings, and electrophysiologic findings of children diagnosed with pediatric-onset hereditary spastic paraplegias (HSPs) at a tertiary pediatric hospital in Japan. The causative gene patterns differed between children with pure-type and complex-type HSPs.
FRONTIERS IN NEUROLOGY
(2023)
Article
Clinical Neurology
Marta Gatti, Stefania Magri, Daniela Di Bella, Elisa Sarto, Franco Taroni, Caterina Mariotti, Lorenzo Nanetti
Summary: SPG46 is a rare autosomal recessive hereditary spastic paraplegia caused by mutations in the GBA2 gene, leading to symptoms such as unsteady gait and spastic-ataxia. The disease presents with distinct clinical features and may overlap with other conditions.
NEUROLOGICAL SCIENCES
(2021)
Review
Neurosciences
Jose Luiz Pedroso, Thiago Cardoso Vale, Marcondes C. Franca Junior, Marcelo A. Kauffman, Helio Teive, Orlando Graziani Povoas Barsottini, Renato Puppi Munhoz
Summary: Spastic ataxia is characterized by the combination of cerebellar ataxia with spasticity and other pyramidal features. This condition can present with heterogeneous clinical features along with other neurologic and non-neurological symptoms, resulting in complex phenotypes. Establishing an organized classification method based on mode of inheritance is essential for approaching patients with these syndromes, and a diagnostic approach is proposed in this review.
Review
Cell Biology
Sonia Sonda, Diana Pendin, Andrea Daga
Summary: The endoplasmic reticulum (ER) is essential for cell function, with its unique membrane architecture playing a critical role. Mutations in ER-shaping proteins have been linked to the neurodegenerative disease hereditary spastic paraplegia (HSP). While some biochemical activities of ER-related HSP proteins have been elucidated, the exact pathological mechanism remains to be determined through further investigation.
Review
Biochemistry & Molecular Biology
Arun Meyyazhagan, Haripriya Kuchi Bhotla, Manikantan Pappuswamy, Antonio Orlacchio
Summary: Hereditary spastic paraplegia (HSP) is an inherited neurodegenerative disease characterized by lower muscle tone and increasing spasticity in the lower limbs. It is associated with changes in about 80 genes and their products involved in various biochemical pathways. HSP can be inherited through autosomal dominant, autosomal recessive, X-linked recessive, or mitochondrial inheritance. The prevalence of HSP is approximately 1-5 cases per 100,000 individuals globally. Current therapies for HSP are based on managing the clinical manifestations, such as muscle relaxation and physiotherapy, but there is still a lack of specific pharmaceutical treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Manuela Wiessner, Reza Maroofian, Meng-Yuan Ni, Andrea Pedroni, Juliane S. Muller, Rolf Stucka, Christian Beetz, Stephanie Efthymiou, Filippo M. Santorelli, Ahmed A. Alfares, Changlian Zhu, Anna Uhrova Meszarosova, Elham Alehabib, Somayeh Bakhtiari, Andreas R. Janecke, Maria Gabriela Otero, Jin Yun Helen Chen, James T. Peterson, Tim M. Strom, Peter De Jonghe, Tine Deconinck, Willem De Ridder, Jonathan De Winter, Rossella Pasquariello, Ivana Ricca, Majid Alfadhel, Bart P. van de Warrenburg, Ruben Portier, Carsten Bergmann, Saghar Ghasemi Firouzabadi, Sheng Chih Jin, Kaya Bilguvar, Sherifa Hamed, Mohammed Abdelhameed, Nourelhoda A. Haridy, Shazia Maqbool, Fatima Rahman, Najwa Anwar, Jenny Carmichael, Alistair Pagnamenta, Nick W. Wood, Frederic Tran Mau-Them, Tobias Haack, Maja Di Rocco, Isabella Ceccherini, Michele Iacomino, Federico Zara, Vincenzo Salpietro, Marcello Scala, Marta Rusmini, Yiran Xu, Yinghong Wang, Yasuhiro Suzuki, Kishin Koh, Haitian Nan, Hiroyuki Ishiura, Shoji Tsuji, Laetitia Lambert, Emmanuelle Schmitt, Elodie Lacaze, Hanna Kuepper, David Dredge, Cara Skraban, Amy Goldstein, Mary J. H. Willis, Katheryn Grand, John M. Graham, Richard A. Lewis, Francisca Millan, Ozgur Duman, Nihal Dundar, Gokhan Uyanik, Ludger Schols, Peter Nuernberg, Gudrun Nuernberg, Andrea Catala Bordes, Pavel Seeman, Martin Kuchar, Hossein Darvish, Adriana Rebelo, Filipa Boucanova, Jean-Jacques Medard, Roman Chrast, Michaela Auer-Grumbach, Fowzan S. Alkuraya, Hanan Shamseldin, Saeed Al Tala, Jamileh Rezazadeh Varaghchi, Maryam Najafi, Selina Deschner, Dieter Glaeser, Wolfgang Huettel, Michael C. Kruer, Erik-Jan Kamsteeg, Yoshihisa Takiyama, Stephan Zuchner, Jonathan Baets, Matthis Synofzik, Rebecca Schuele, Rita Horvath, Henry Houlden, Luca Bartesaghi, Hwei-Jen Lee, Konstantinos Ampatzis, Tyler Mark Pierson, Jan Senderek
Summary: This study identified families with neurological diseases caused by HPDL variants, showing various phenotypes ranging from juvenile-onset pure hereditary spastic paraplegia to infantile-onset spastic tetraplegia. Experimental evidence suggested a role of HPDL in the nervous system and supported its link to neurological disease.
Article
Clinical Neurology
Katiane R. Servelhere, Thiago Junqueira Ribeiro Rezende, Fabricio Diniz de Lima, Mariana Rabelo de Brito, Renan Flavio de Franca Nunes, Raphael F. Casseb, Jose Luiz Pedroso, Orlando Graziani P. Barsottini, Fernando Cendes, Marcondes C. Franca Jr
Summary: HSPs are characterized by brain damage, with genotype-specific patterns of abnormalities. Most HSP patients show brain and cerebellar involvement, with distinct damage patterns based on genetic subtypes.
MOVEMENT DISORDERS
(2021)
Article
Clinical Neurology
Shao-Lun Hsu, Yi-Chu Liao, Kon-Ping Lin, Po-Yu Lin, Kai-Wei Yu, Yu-Shuen Tsai, Yuh-Cherng Guo, Yi-Chung Lee
Summary: The study revealed that SPG30 is a rare subtype of HSP in Taiwan, accounting for approximately 1.2% of patients. Mutations in the KIF1A gene may lead to hereditary HSP, presenting with complex symptoms including additional neuropathy. The research provides valuable insights into the clinical and genetic features of SPG30 in Taiwan, especially in Han Chinese patients.
PARKINSONISM & RELATED DISORDERS
(2022)
Article
Medicine, General & Internal
A. Legrand, C. Pujol, C. M. Durand, A. Mesnil, I. Rubera, C. Duranton, S. Zuily, A. B. Sousa, M. Renaud, J. L. Boucher, N. Pietrancosta, S. Adham, C. Orssaud, C. Marelli, C. Casali, L. Ziccardi, N. Villain, C. Ewenczyk, A. Durr, C. Mignot, G. Stevanin, C. Billon, M. Hureaux, X. Jeunemaitre, C. Goizet, J. Albuisson
Summary: A study identified CYP2U1 pathogenic variants in PXE patients with neurological symptoms who were unresolved by ABCC6 genetic screening, expanding the phenotype of SPG56 and highlighting its overlap with PXE. The pathophysiology of ABCC6 and CYP2U1 should be explored further to understand their respective roles and potential interaction in ectopic mineralization.
JOURNAL OF INTERNAL MEDICINE
(2021)
Article
Neurosciences
Gautam Wali, Sue-Faye Siow, Erandhi Liyanage, Kishore R. R. Kumar, Alan Mackay-Sim, Carolyn M. M. Sue
Summary: HSP-SPAST is the most common form of hereditary spastic paraplegia (HSP), causing lower limb spasticity. Both patient-derived cortical neurons and peripheral blood mononuclear cells (PBMCs) show reduced levels of acetylated alpha-tubulin, which can be restored by noscapine treatment. Noscapine treatment can potentially benefit HSP-SPAST patients by increasing acetylated alpha-tubulin levels.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Audiology & Speech-Language Pathology
Leonardo Wanderley Lopes, Allan Carlos Franca da Silva, Itacely Marinho da Silva, Maxsuel Alves Avelino de Paiva, Saulo Iordan do Nascimento Silva, Larissa Nadjara Alves Almeida, Vanessa Veis Ribeiro
Summary: This study verified the validity of internal consistency in the spectrographic analysis protocol (SAP). Participants evaluated and analyzed the relationship between items in the SAP. The results showed a good relationship between most items and the overall protocol. However, a few items had lower values, indicating a need for further training to properly understand these items.
Letter
Rheumatology
Martin Sebastian Winkler, Peter Korsten, Claudia Binder, Bjoern Tampe
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Oncology
Yi Liao, Senmao Li, Hao Chen, Chunyu Chen, Jintuan Huang, Feng Lin, Jianping Wang, Zuli Yang
Summary: A risk prediction system combining FIT and risk factors was developed to improve the sensitivity of colonoscopy screening. The system effectively stratified participants into high risk and low risk groups, with better predictive ability for colorectal neoplasia compared to using FIT alone.
EUROPEAN JOURNAL OF CANCER PREVENTION
(2023)
Article
Oncology
Luca Giraldi, Jovana Stojanovic, Dario Arzani, Roberto Persiani, Jinfu Hu, Kenneth C. Johnson, Zuo-Feng Zhang, Monica Ferraroni, Domenico Palli, Guo-Pei Yu, Carlo La Vecchia, Claudio Pelucchi, Nuno Lunet, Ana Ferro, Reza Malekzadeh, Joshua Muscat, David Zaridze, Dmitry Maximovich, Nuria Aragones, Vicente Martin, Jesus Vioque, Eva M. Navarrete-Munoz, Mohammadreza Pakseresht, Eva Negri, Matteo Rota, Farhad Pourfarzi, Lina Mu, Robert C. Kurtz, Areti Lagiou, Pagona Lagiou, Roberta Pastorino, Stefania Boccia
Summary: This study aimed to examine the association between height and risk of gastric cancer. Through a large pooled analysis of case-control studies, the study found no significant association between adult height and gastric cancer.
EUROPEAN JOURNAL OF CANCER PREVENTION
(2023)
Article
Oncology
Maria A. Karalexi, Marina Servitzoglou, Vassilios Papadakis, Denis Kachanov, Maja Cesen Mazic, Margaret Baka, Maria Moschovi, Maria Kourti, Sofia Polychronopoulou, Eftichia Stiakaki, Emmanuel Hatzipantelis, Helen Dana, Kalliopi Stefanaki, Astero Malama, Marios S. Themistocleous, Katerina Strantzia, Tatyana Shamanskaya, Panagiota Bouka, Paraskevi Panagopoulou, Maria Kantzanou, Evangelia Ntzani, Nick Dessypris, Eleni Th. Petridou
Summary: The prognosis of children with neuroblastoma varies depending on the stage and biology of the tumor, and early-stage neuroblastoma has a better prognosis. Treatment with anti-GD2 antibody can improve the prognosis of high-risk patients.
EUROPEAN JOURNAL OF CANCER PREVENTION
(2023)
Article
Ophthalmology
Aniruddha Agarwal, Sabia Handa, Giuseppe Querques, Vishali Gupta
Summary: This article describes a case of a male patient who presented with metamorphopsia in the right eye. Various examinations revealed different types of drusen and structural changes. No further changes were observed during follow-up. The authors highlighted that in some cases, serous detachments may occur even without macular neovascularization.
EUROPEAN JOURNAL OF OPHTHALMOLOGY
(2022)
Article
Emergency Medicine
Barbara Eaton, Lindsay O'Meara, Carla Aresco, Thomas Scalea, Jose Diaz, Brandon Bruns
Summary: In 2017, a quality structure was formalized with a focus on scheduled quality meetings, peer review, and outcomes review. All admission, service-specific dashboards, and readmission data were manually audited by SB APPs to confirm accuracy and identify opportunities for process improvement.
EUROPEAN JOURNAL OF TRAUMA AND EMERGENCY SURGERY
(2022)
Article
Chemistry, Applied
Renato Sonchini Goncalves, Ana Carolina Vieira de Oliveira, Noboru Hioka, Wilker Caetano
Summary: This study investigated the behavior of HYP-loaded P84 micelles using 1D and 2D NMR techniques, and found that HYP molecules were arranged in a pi-stacked aggregation form on the core of P84 micelles.
NATURAL PRODUCT RESEARCH
(2022)
Review
Clinical Neurology
Christoph Eckhard Heyde, Ulrich Josef Albert Spiegl, Anna Voelker, Nicolas von der Hoeh, Jeanette Henkelmann
Summary: The prevalence of nonspecific pyogenic spondylodiskitis has increased, causing high morbidity and mortality. The diagnosis is often delayed due to nonspecific clinical manifestations at the early stage. CT can assess the bony condition, while MRI is still the gold standard for diagnosis.
JOURNAL OF NEUROLOGICAL SURGERY PART A-CENTRAL EUROPEAN NEUROSURGERY
(2023)
Article
Clinical Neurology
Thiago J. R. Rezende, Isaac M. Adanyeguh, Filippo Arrigoni, Benjamin Bender, Fernando Cendes, Louise A. Corben, Andreas Deistung, Martin Delatycki, Imis Dogan, Gary F. Egan, Sophia L. Goericke, Nellie Georgiou-Karistianis, Pierre-Gilles Henry, Diane Hutter, Neda Jahanshad, James M. Joers, Christophe Lenglet, Tobias Lindig, Alberto R. M. Martinez, Andrea Martinuzzi, Gabriella Paparella, Denis Peruzzo, Kathrin Reetz, Sandro Romanzetti, Ludger Schoels, Joerg B. Schulz, Matthis Synofzik, Sophia I. Thomopoulos, Paul M. Thompson, Dagmar Timmann, Ian H. Harding, Marcondes C. Franca
Summary: This study characterized cervical spinal cord structural damage in a large multisite cohort of Friedreich's ataxia (FRDA) patients. The results showed that FRDA patients had significantly reduced cross-sectional area (CSA) and increased eccentricity in the cervical spinal cord compared to control subjects. The CSA had significant correlations with disease severity, while eccentricity did not. Subgroup analyses revealed abnormal CSA and eccentricity at all disease stages, with CSA appearing to decrease progressively and eccentricity remaining stable over time.
MOVEMENT DISORDERS
(2023)
Article
Behavioral Sciences
Thamires Naela Cardoso Magalhaes, Raphael Fernandes Casseb, Christian Luiz Baptista Gerbelli, Luciana Ramalho Pimentel-Siva, Mateus Henrique Nogueira, Camila Vieira Ligo Teixeira, Ana Flavia Mac Knight Carletti, Thiago Junqueira Ribeiro de Rezende, Helena Passarelli Giroud Joaquim, Leda Leme Talib, Orestes Vicente Forlenza, Fernando Cendes, Marcio Luiz Figueredo Balthazar
Summary: The causes of neurodegenerative processes in Alzheimer's disease are not fully understood. Recent studies have shown that damage in white matter may be more severe and widespread than cortical atrophy in the brain, appearing even before gray matter damage. Amyloid-beta and tau proteins in AD can directly affect white matter and spread across brain networks. This study aimed to evaluate whole-brain white matter integrity using diffusion tensor imaging in mild AD and amnestic mild cognitive impairment (aMCI) due to AD. Widespread white matter alterations were found, with correlations between tau proteins and tracts linked to the mesial temporal lobe. However, hippocampal volume better explained the variation in diffusion tensor imaging measures compared to CSF proteins.
BRAIN AND BEHAVIOR
(2023)
Article
Neurosciences
Jose Thiago de Souza de Castro, Camilo Lot fi Saab, Mariam Patricia Auada Souto, Juliane Giselle Ortolam, Carlos Eduardo Steiner, Thiago Junqueira Ribeiro de Rezende, Fabiano Reis
Summary: In this study, volumetric analysis of the brain was performed on two siblings with SLS, revealing volume reduction in deep grey matter nuclei, cerebellar grey matter, and brainstem. This suggests that SLS is not solely a leukoencephalopathy, but also involves dysfunction in thalamic motor pathways.
ARQUIVOS DE NEURO-PSIQUIATRIA
(2023)
Article
Neurosciences
Alexandra Prufer de Queiroz Campos Araujo, Jonas Alex Morales Saute, Clarisse Pereira Dias Drumond Fortes, Marcondes Cavalcante Franca Jr, Jaqueline Almeida Pereira, Marco Antonio Veloso de Albuquerque, Alzira Alves de Siqueira Carvalho, Eduardo Boiteux Uchoa Cavalcanti, Anna Paula Paranhos Miranda Covaleski, Simone Chaves Fagondes, Juliana Gurgel-Giannetti, Marcus Vinicius Magno Goncalves, Alberto Rolim Muro Martinez, Antonio Rodrigues Coimbra Neto, Flavio Reis Neves, Anamarli Nucci, Ana Paula Cassetta dos Santos Nucera, Andre Luis Santos Pessoa, Marcos Ferreira Rebel, Flavia Nardes dos Santos, Rosana Herminia Scola, Claudia Ferreira da Rosa Sobreira
Summary: In recent decades, there have been significant improvements in the diagnosis and care of Duchenne muscular dystrophy (DMD). International guidelines have been published and reviewed, and Brazilian experts have developed evidence-based recommendations for care. Implementing best practice management and new treatments has changed the natural history of DMD, improving life expectancy. In this document, the previous care recommendations for Brazilian patients with DMD are reviewed and updated.
ARQUIVOS DE NEURO-PSIQUIATRIA
(2023)
