Article
Clinical Neurology
Carolyn Daniels, Caitlin Greene, Lacey Smith, Elia Pestana-Knight, Scott Demarest, Bo Zhang, Timothy A. Benke, Annapurna Poduri, Heather E. Olson
Summary: This study aimed to differentiate individuals with CDKL5 deficiency disorder (CDD) from those with other infantile-onset epilepsies based on their phenotypic features. The results showed that CDD individuals were more likely to have treatment-resistant epilepsy, developmental and epileptic encephalopathy, sequential seizures, spasms without hypsarrhythmia, diffuse hypotonia, paroxysmal movement disorders, cerebral visual impairment, and failure to thrive compared to the comparison group. Defining core phenotypic characteristics can improve precision diagnosis and treatment.
DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY
(2023)
Article
Clinical Neurology
Alessandra Morano, Emanuele Cerulli Irelli, Enrico Michele Salamone, Biagio Orlando, Martina Fanella, Emanuele Tinelli, Gabriele Ruffolo, Luigi Zuliani, Jinane Fattouch, Mario Manfredi, Anna Teresa Giallonardo, Carlo Di Bonaventura
Summary: This study compares patients with autoimmune encephalitis (AE) and late-onset epilepsy of unknown origin (LOEUO) and finds that high-frequency focal seizures with autonomic manifestations may be indicative of AE in the elderly. It highlights the importance of using 24-h ambulatory electroencephalography (AEEG) to recognize AE and reduce diagnostic delay.
FRONTIERS IN NEUROLOGY
(2022)
Review
Behavioral Sciences
Alain Lekoubou, Kunal Debroy, Abena Kwegyir-Aggrey, Leonardo Bonilha, Andre Pascal Kengne, Vernon M. Chinchilli
Summary: This systematic review evaluated risk models for predicting late seizures in stroke survivors, including models for both ischemic and hemorrhagic strokes. The SeLECT model showed promising results, but further validation in diverse populations is needed for clinical application.
EPILEPSY & BEHAVIOR
(2021)
Article
Clinical Neurology
Marie Suesse, Maria Zank, Viola von Podewils, Felix von Podewils
Summary: Late-onset seizures due to autoimmune encephalitis (AE) are associated with mesial temporal neuropsychological deficits, malignancy, pleocytosis, and oligoclonal bands in cerebrospinal fluid. Patients with AE showed favorable outcome with antiseizure drug and immunosuppressive therapy, highlighting the importance of neural antibody testing, neuroimaging, cerebrospinal fluid analysis, and neuropsychological testing in the diagnostic protocol for AE following late-onset seizures.
FRONTIERS IN NEUROLOGY
(2021)
Article
Clinical Neurology
Emily L. Johnson, Kevin J. Sullivan, Andrea Lauren Christman Schneider, Jeannette Simino, Tom H. Mosley, Anna Kucharska-Newton, David S. Knopman, Rebecca F. Gottesman
Summary: This study aimed to investigate the relationship between plasma beta-amyloid (A beta) and late-onset epilepsy (LOE). The findings suggest that a decrease in plasma A beta(42)/A beta(40) ratio is associated with an increased risk of epilepsy in later life.
Article
Clinical Neurology
Emily L. Johnson, Gregory L. Krauss, Anna Kucharska-Newton, Alice D. Lam, Rani Sarkis, Rebecca F. Gottesman
Summary: Individuals with late-onset epilepsy (LOE) have a higher risk of mortality compared to those without epilepsy, primarily due to stroke and dementia.
Article
Clinical Neurology
Andrea L. C. Schneider, Rebecca F. Gottesman, Gregory L. Krauss, James Gugger, Ramon Diaz-Arrastia, Anna Kucharska-Newton, Juebin Huang, Emily L. Johnson
Summary: This study demonstrates an association between head injury and late-onset epilepsy, particularly when the head injuries occur at an older age. Multiple and more severe head injuries further increase the risk of developing late-onset epilepsy.
Article
Neurosciences
Marianna Tassinari, Beatrice Uguagliati, Stefania Trazzi, Camilla Bruna Cerchier, Ottavia Vera Cavina, Nicola Mottolese, Manuela Loi, Giulia Candini, Giorgio Medici, Elisabetta Ciani
Summary: Mutations in CDKL5 gene cause CDKL5 deficiency disorder characterized by early-onset epilepsy, motor impairment, intellectual disability, and autistic features. A mouse model of CDD has revealed brain alterations leading to neurological defects and showed that most of the structural alterations are already present in pups aged 7 days and do not worsen with age.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Clinical Neurology
Masanori Maeda, Tohru Okanishi, Yosuke Miyamoto, Takuya Hayashida, Tatsuya Kawaguchi, Sotaro Kanai, Yoshiaki Saito, Yoshihiro Maegaki
Summary: The study found significant differences in NH3, BS, Cr levels, WBC count, and pH between AESD and FS patients at <3 h from onset. The scoring system using these data can accurately predict AESD onset.
FRONTIERS IN NEUROLOGY
(2021)
Article
Neurosciences
Barbara Terzic, Yue Cui, Andrew C. Edmondson, Sheng Tang, Nicolas Sarmiento, Daria Zaitseva, Eric D. Marsh, Douglas A. Coulter, Zhaolan Zhou
Summary: CDKL5 deficiency disorder (CDD) is a disease characterized by infantile onset seizures, intellectual disability, and motor impairments. Research in mouse models has replicated many aspects of the disorder's symptoms, and a recent study observed disturbance-associated seizure-like events in heterozygous female mice. The prevalence and severity of these events increase with age, highlighting the importance of X-linked cellular mosaicism in driving this phenotype.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Medicine, Research & Experimental
Barbara Terzic, M. Felicia Davatolhagh, Yugong Ho, Sheng Tang, Yu-Ting Liu, Zijie Xia, Yue Cui, Marc Fuccillo, Zhaolan Zhou
Summary: This study found that CDKL5 plays an indispensable role in the adult brain, and postdevelopmental loss of CDKL5 can lead to behavioral impairments and neural signaling abnormalities. Partial improvement of these issues was observed using a conditional rescue mouse model, suggesting a potential for reversal of CDD-related deficits.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Clinical Neurology
Elia M. Pestana Knight, Sam Amin, Nadia Bahi-Buisson, Tim A. Benke, J. Helen Cross, Scott T. Demarest, Heather E. Olson, Nicola Specchio, Thomas R. Fleming, Alex A. Aimetti, Maciej Gasior, Orrin Devinsky
Summary: This study evaluated the efficacy and safety of ganaxolone in patients with CDKL5 deficiency disorder (CDD) and refractory epilepsy. The results showed that ganaxolone significantly reduced seizure frequency in CDD patients and was generally well tolerated. The study suggests a potential treatment benefit for ganaxolone in CDD and further long-term treatment is being assessed in the ongoing open-label extension phase.
Article
Neurosciences
Valeria Ruggiero, Claudio Fagioli, Stefano de Pretis, Valerio Di Carlo, Nicoletta Landsberger, Daniele Zacchetti
Summary: CDKL5 is an important kinase involved in neuronal development and synapse formation. Decreased expression or activity of CDKL5 leads to severe neurodevelopmental disorders. This study investigates the translational regulation of CDKL5 and identifies important elements and factors involved. The findings provide insights into the physiological processes and pathogenesis related to CDKL5 deficiency disorder.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Clinical Neurology
Lorna Myers, Robert Trobliger, Marcelo Lancman
Summary: The study found that patients who experienced sexual trauma were more likely to develop PNES at a younger age, while those with health problems before PNES onset were more likely to develop PNES at an older age. The groups with different age of onset differed in psychological measures and trauma experiences.
SEIZURE-EUROPEAN JOURNAL OF EPILEPSY
(2021)
Review
Clinical Neurology
William Hong, Isabel Haviland, Elia Pestana-Knight, Judith L. Weisenberg, Scott Demarest, Eric D. Marsh, Heather E. Olson
Summary: Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a developmental and epileptic encephalopathy with infantile-onset epilepsy. The management of seizures in CDD is challenging due to their highly refractory nature and limited evidence-based treatment options.
Review
Pathology
Joanne Traeger-Synodinos, Cornelis L. Harteveld
EXPERT REVIEW OF MOLECULAR DIAGNOSTICS
(2017)
Article
Obstetrics & Gynecology
G. Kakourou, S. Kahraman, G. C. Ekmekci, H. A. Tac, G. Kourlaba, E. Kourkouni, A. Cervero Sanz, J. Martin, H. Malmgren, C. Gimenez, V. Gold, F. Carvalho, C. Billi, J. F. C. Chow, X. Vendrell, G. Kokkali, J. Liss, J. Steffann, J. Traeger-Synodinos
HUMAN REPRODUCTION
(2018)
Article
Hematology
C. Vrettou, G. Kakourou, T. Mamas, J. Traeger-Synodinos
INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY
(2018)
Article
Biochemistry & Molecular Biology
Alexandros Makis, Ioannis Georgiou, Jan Traeger-Synodinos, Maria Rosaria Storino, Mariarosaria Giuliano, Immacolata Andolfo, Eleftheria Hatzimichael, Nikolaos Chaliasos, Vasileios Giapros, Paola Izzo, Achille Iolascon, Michela Grosso
Summary: This study describes a novel deletion causing heterozygous epsilon gamma delta beta-thalassemia in a Greek family across three generations. The deletion led to severe but transient neonatal anemia and later in life non transfusion-dependent chronic hemolytic anemia. The challenges involving clinical management are also discussed, highlighting the unique characteristics of this type of thalassemia.
Article
Genetics & Heredity
Petros Kountouris, Coralea Stephanou, Carsten W. Lederer, Joanne Traeger-Synodinos, Celeste Bento, Cornelis L. Harteveld, Eirini Fylaktou, Tamara T. Koopmann, Hashim Halim-Fikri, Kyriaki Michailidou, Landry E. Nfonsam, John S. Waye, Bin A. Zilfalil, Marina Kleanthous
Summary: This article discusses the experience of the ClinGen Variant Curation Expert Panel in adapting ACMG/AMP criteria for classifying variants in three globin genes related to recessively inherited hemoglobinopathies, using five evidence categories as examples to demonstrate the process of specification and rationale underlying the classification.
Review
Hematology
Thalia Mamas, Georgia Kakourou, Christina Vrettou, Joanne Traeger-Synodinos
Summary: Hemoglobinopathies are common inherited disorders that are difficult to manage and treat. Preimplantation genetic testing for monogenic disorders (PGT-M) is a valuable reproductive option for couples carrying hemoglobinopathy genes. PGT-M has evolved over the years, allowing for the simultaneous diagnosis of hemoglobinopathies and screening for chromosomal abnormalities in embryos, with the aim of improving success rates and increasing the number of unaffected babies born.
INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Georgios K. Papadimas, Constantinos Papadopoulos, Kyriaki Kekou, Chrisoula Kartanou, Athina Kladi, Evangelia Nitsa, Christalena Sofocleous, Evangelia Tsanou, Ioannis Sarmas, Stefania Kaninia, Elisabeth Chroni, Georgios Tsivgoulis, Vasilios Kimiskidis, Marianthi Arnaoutoglou, Leonidas Stefanis, Marios Panas, Georgios Koutsis, Georgia Karadima, Joanne Traeger-Synodinos
Summary: This study retrospectively analyzed the medical records of 561 Greek patients with myotonic dystrophies. The findings show similarities in clinical and genetic characteristics between these patients and those from other regions. Muscle weakness is the first symptom in both types of myotonic dystrophies, while multisystemic involvement and cataracts are common manifestations. The study highlights the importance of specialized neuromuscular centers that can provide genetic counseling and a multidisciplinary approach.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Chrisoula Kartanou, Maria Seferiadi, Stella Pomoni, Constantin Potagas, Chrystalena Sofocleous, Joanne Traeger-Synodinos, Leonidas Stefanis, Marios Panas, Georgios Koutsis, Georgia Karadima
Summary: This study investigates the frequency, genotypic and phenotypic profile of FXTAS in two cohorts of Greek patients with late-onset movement disorders and suggests that FXTAS is an important, albeit rare, cause of late-onset movement disorders. It highlights the importance of FMR1 genetic testing in the diagnosis of late-onset movement disorders.
PARKINSONISM & RELATED DISORDERS
(2023)
Article
Biology
Stella Tamana, Maria Xenophontos, Anna Minaidou, Coralea Stephanou, Cornelis L. Harteveld, Celeste Bento, Joanne Traeger-Synodinos, Irene Fylaktou, Norafiza Mohd Yasin, Faidatul Syazlin Abdul Hamid, Ezalia Esa, Hashim Halim-Fikri, Bin Alwi Zilfalil, Andrea C. Kakouri, Marina Kleanthous, Petros Kountouris
Summary: This study evaluates the performance of 31 in silico predictors in globin gene clusters. The results show that CADD, Eigen-PC, and REVEL are the overall top performers, while SpliceAI is the best splicing predictor, and GERP++ and phyloP are the most accurate conservation tools. The study provides evidence about the optimal use of these computational tools under the ACMG/AMP framework.
Article
Genetics & Heredity
Faidon-Nikolaos Tilemis, Nikolaos M. M. Marinakis, Konstantina Kosma, Florentia Fostira, Joanne Traeger-Synodinos
Summary: Non-syndromic polydactyly is associated with pathogenic variants in IQCE gene, and this case report identifies a pathogenic IQCE variant and a large deletion involving IQCE gene using whole-exome sequencing. The IQCE gene codes for a protein that positively regulates the Hedgehog signaling pathway at the base of the primary cilia. This study highlights the importance of using ExomeDepth in routine WES analysis for diagnosing rare genetic diseases.
MOLECULAR SYNDROMOLOGY
(2023)
Editorial Material
Biochemistry & Molecular Biology
Periklis Makrythanasis, Georgia Kakourou, Thalia Mamas, Christina Vrettou, Jan Traeger-Synodinos
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Genetics & Heredity
Faidon-Nikolaos Tilemis, Nikolaos M. Marinakis, Danai Veltra, Maria Svingou, Kyriaki Kekou, Anastasios Mitrakos, Maria Tzetis, Konstantina Kosma, Periklis Makrythanasis, Joanne Traeger-Synodinos, Christalena Sofocleous
Summary: The integration of whole-exome sequencing (WES) and sensitive bioinformatic tools has enabled the detection of copy number variants (CNVs) in patients with rare diseases (RDs), improving the diagnostic yield of WES.
Article
Genetics & Heredity
Athanasios Goumenos, Eirini Tsoutsou, Joanne Traeger-Synodinos, Dimitrios Petychakis, Maria Gavra, Aggeliki Kolialexi, Helena Frysira
APPLICATION OF CLINICAL GENETICS
(2019)
Article
Obstetrics & Gynecology
Georgia Kakourou, Christina Vrettou, Maria Moutafi, Joanne Traeger-Synodinos
BEST PRACTICE & RESEARCH CLINICAL OBSTETRICS & GYNAECOLOGY
(2017)
Article
Genetics & Heredity
Carlo Vermeulen, Geert Geeven, Elzo de Wit, Marjon J. A. M. Verstegen, Rumo P. M. Jansen, Melissa van Kranenburg, Ewart de Bruijn, Sara L. Pulit, Evelien Kruisselbrink, Zahra Shahsavari, Davood Omrani, Fatemeh Zeinali, Hossein Najmabadi, Theodora Katsila, Christina Vrettou, George P. Patrinos, Joanne Traeger-Synodinos, Erik Splinter, Jeffrey M. Beekman, Sima Kheradmand Kia, Gerard J. te Meerman, Hans Kristian Ploos van Amstel, Wouter de Laat
AMERICAN JOURNAL OF HUMAN GENETICS
(2017)
Article
Clinical Neurology
Karlijn Bouman, Jeroen L. M. van Doorn, Jan T. Groothuis, Peter J. Wijkstra, Baziel G. M. van Engelen, Corrie E. Erasmus, Jonne Doorduin, Nicol C. Voermans
Summary: The majority of LAMA2-MD and all SELENON-RM patients had respiratory impairment. SELENON-RM patients showed lower respiratory function which was progressive, more prevalent mechanical ventilation, and more severe diaphragm atrophy and dysfunction than LAMA2-MD patients. Spirometry (FVC%, dVC) and respiratory muscle strength tests (SNIP) are useful in clinical care and as outcome measure in clinical trials.
EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY
(2024)
Article
Clinical Neurology
Oliviero Bruni, Maria Breda, Emanuela Malorgio, Paolo Brambilla, Flavia Ceschin, Andrea Di Pilla, Maurizio Elia, Raffaele Ferri
Summary: This study aimed to describe the use of melatonin by Italian pediatricians in healthy children with chronic insomnia. The results showed that a high percentage of pediatricians prescribed melatonin, especially in children aged 1-2 years. The most common dosage was 1 mg/day and it was usually recommended to be taken 30 minutes before bedtime. Melatonin was often combined with sleep hygiene and was found to be effective in reducing difficulties falling asleep.
EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY
(2024)
Article
Clinical Neurology
Lucie Sedlackova, Katalin Sterbova, Marketa Vlckova, Pavel Seeman, Jana Zarubova, Petr Marusic, Pavel Krsek, Hana Krijtova, Alena Musilova, Petra Lassuthova
Summary: In this study, whole exome sequencing (WES) was performed to identify causal variants for developmental and epileptic encephalopathies (DEEs) in patients whose genetic diagnosis was not determined by gene panel testing. The results showed that WES can successfully identify disease-causing variants, even after inconclusive gene panel testing. Detailed clinical evaluations and phenotype-genotype correlation studies were conducted to better understand the rare subtypes of DEEs.
EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY
(2024)
