Article
Clinical Neurology
Satoru Takahashi, Ryo Takeguchi, Ryosuke Tanaka, Masataka Fukuoka, Takayoshi Koike, Hideyuki Ohtani, Kenji Inoue, Mitsumasa Fukuda, Hirokazu Kurahashi, Kazuyuki Nakamura, Koji Tominaga, Tomoko Matsubayashi, Masayuki Itoh, Teruyuki Tanaka
Summary: This study examines the impact of genetic variants on the clinical phenotype of patients with CDKL5 deficiency disorder (CDD) and finds that cellular mosaicism is associated with lesser severity of comorbidities, but not necessarily required for developing epilepsy.
JOURNAL OF THE NEUROLOGICAL SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Wenlin Liao, Kun-Ze Lee
Summary: Cyclin-dependent kinase-like 5 (CDKL5) is an important regulator in neuronal development and function. Patients with CDKL5 deficiency disorder (CDD) often present with early-onset epilepsy. However, mouse models of CDD have not shown spontaneous seizures. In this study, the researchers found that mice lacking CDKL5 exhibited spontaneous epileptic EEG discharges at postnatal day 12, but these spikes disappeared after postnatal day 14. Transcriptome profiling revealed age-dependent and brain region-specific alterations of gene expression. These findings provide new insights into the etiology of CDD and potential targets for the treatment of neonatal epilepsy.
HUMAN MOLECULAR GENETICS
(2023)
Article
Pediatrics
Malgorzata Rodak, Mariola Jonderko, Patrycja Rozwadowska, Magdalena Machnikowska-Sokolowska, Justyna Paprocka
Summary: CDKL5 deficiency disorder is a rare developmental brain disease caused by mutations in the CDKL5 gene, primarily affecting females. We report an unreported case of a male patient diagnosed with this disease at the age of 2.5, presenting with drug-resistant epilepsy and severe developmental delay.
Article
Biochemistry & Molecular Biology
Sara Carli, Linda Chaabane, Clarissa Butti, Clara De Palma, Patrizia Aimar, Chiara Salio, Aglaia Vignoli, Maurizio Giustetto, Nicoletta Landsberger, Angelisa Frasca
Summary: CDKL5 deficiency disorder is a severe neurodevelopmental condition caused by mutations in the X-linked CDKL5 gene, characterized by infantile epileptic encephalopathy, intellectual disability, and autistic features. Magnetic Resonance methods revealed a metabolic dysregulation suggestive of mitochondrial dysfunction in the brain of Cdkl5 deficient mice, highlighting potential therapeutic strategies targeting mitochondria.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Clinical Neurology
Eveline E. O. Hagebeuk, Annelies Smits, Al de Weerd
Summary: This study examined sleep disturbances and respiratory function in Dutch children with CDKL5 deficiency disorder (CDD) over a period of 5-10 years. The results showed that sleep disturbances persisted and breathing disturbances also occurred during wakefulness. These sleep problems have a significant impact on the emotional well-being and quality of life of both the individuals with CDD and their caregivers.
Article
Neurosciences
Nicola Specchio, Marina Trivisano, Matteo Lenge, Alessandro Ferretti, Davide Mei, Elena Parrini, Antonio Napolitano, Camilla Rossi-Espagnet, Giacomo Talenti, Daniela Longo, Jacopo Proietti, Francesca Ragona, Elena Freri, Roberta Solazzi, Tiziana Granata, Francesca Darra, Bernardo Dalla Bernardina, Federico Vigevano, Renzo Guerrini
Summary: This study analyzed the clinical phenotype of Cyclin-Dependent Kinase-Like 5 (CDKL5) deficiency disorder (CDD) and found that brain magnetic resonance imaging (MRI) showed a reduction in brain volume, which may be related to both the pathogenesis of CDD and the severity of epilepsy.
Article
Clinical Neurology
Heather E. E. Olson, Scott Demarest, Elia Pestana-Knight, Ahsan N. N. Moosa, Xiaoming Zhang, Jose R. Perez-Perez, Judy Weisenberg, Erin O'Connor Prange, Eric D. D. Marsh, Rajsekar R. R. Rajaraman, Bernhard Suter, Akshat Katyayan, Isabel Haviland, Carolyn Daniels, Bo Zhang, Caitlin Greene, Michelle DeLeo, Lindsay Swanson, Jamie Love-Nichols, Timothy Benke, Chellamani Harini, Annapurna Poduri
Summary: The study aimed to compare the treatment response of infantile-onset epileptic spasms (ES) in CDKL5 deficiency disorder (CDD) with other etiologies. Patients from CDKL5 Centers of Excellence and the National Infantile Spasms Consortium (NISC) were evaluated for time to treatment and ES remission at 14 days and 3 months. Results showed that children with ES in the setting of CDD often experience longer lead time to treatment and respond poorly to standard treatments, highlighting the need for alternative treatments.
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
Helen Leonard, Mohammed Junaid, Kingsley Wong, Scott Demarest, Jenny Downs
Summary: CDKL5 Deficiency Disorder is a rare genetic disorder characterized by early onset seizures and severe developmental delay. Factors such as functional impairment, the number of anti-epileptic medications used, and geographical region were found to be associated with quality of life in individuals with this disorder.
Article
Clinical Neurology
Helen Leonard, Mohammed Junaid, Kingsley Wong, Alex A. Aimetti, Elia Pestana Knight, Jenny Downs
Summary: This study found that patients with better early seizure control showed slightly improved development later, suggesting that an individual child's trajectory is not necessarily predetermined and could possibly be influenced by optimal seizure management. This has implications for children's quality of life.
Article
Clinical Neurology
Orrin Devinsky, LaToya King, Danielle Schwartz, Erin Conway, Dana Price
Summary: This study evaluated the efficacy of fenfluramine in treating uncontrolled seizures in patients with CDKL5 deficiency disorder. The results suggest that fenfluramine may be a promising antiseizure medication for CDD, as it significantly reduced seizure frequency in some patients but with some adverse events. Further randomized clinical trials are needed to confirm these findings.
Article
Cell & Tissue Engineering
Pin-Fang Chen, Teresa Chen, Taylor E. Forman, Amanda C. Swanson, Benjamin O'Kelly, Sean A. Dwyer, Elizabeth D. Buttermore, Robin Kleiman, Sheridan J. S. Carrington, Daniel J. Lavery, Lindsay C. Swanson, Heather E. Olson, Mustafa Sahin
Summary: This report documents the generation and characterization of induced pluripotent stem cells (iPSCs) derived from fibroblasts of six unrelated CDD patients, including three males and three females, who are clinically diagnosed with classic CDD phenotypes such as refractory epilepsy and global developmental delay. These patients are part of a longitudinal clinical study.
STEM CELL RESEARCH
(2021)
Article
Behavioral Sciences
Jacinta M. Saldaris, Peter Jacoby, Helen Leonard, Tim A. Benke, Scott Demarest, Eric D. Marsh, Jenny Downs
Summary: This study aimed to evaluate the psychometric properties of the Quality of Life Inventory-Disability (QI-Disability) in CDKL5 Deficiency Disorder (CDD). The results showed that QI-Disability is suitable for assessing the quality of life of children and adults with CDD and may be of value for upcoming clinical trials.
EPILEPSY & BEHAVIOR
(2023)
Article
Clinical Neurology
Heather E. Olson, Carolyn Daniels, Isabel Haviland, Lindsay C. Swanson, Caitlin A. Greene, Anne Marie M. Denny, Scott T. Demarest, Elia Pestana-Knight, Xiaoming Zhang, Ahsan N. Moosa, Andrea Fidell, Judith L. Weisenberg, Bernhard Suter, Cary Fu, Jeffrey L. Neul, Alan K. Percy, Eric D. Marsh, Timothy A. Benke, Annapurna Poduri
Summary: The treatment for neurological features of CDD is currently symptom-based and empirical, not specific to CDD. Anti-seizure medications are commonly used, with ketogenic diet also being a common treatment approach. There is limited information on medications for sleep, behavioral management, and movement disorders, highlighting the need for further research in these areas.
JOURNAL OF NEURODEVELOPMENTAL DISORDERS
(2021)
Article
Clinical Neurology
Sam Amin, Marie Monaghan, Angel Aledo-Serrano, Nadia Bahi-Buisson, Richard F. Chin, Angus J. Clarke, J. Helen Cross, Scott Demarest, Orrin Devinsky, Jenny Downs, Elia M. Pestana Knight, Heather Olson, Carol-Anne Partridge, Graham Stuart, Marina Trivisano, Sameer Zuberi, Tim A. Benke
Summary: This article presents the characteristics, incidence, and impact of CDKL5 Deficiency Disorder (CDD), as well as recommendations from international healthcare professionals to address the diverse needs of individuals with CDD. Using a Delphi method, a consensus was reached and clinical management recommendations were proposed. These recommendations aim to standardize and improve the medical care for individuals with CDD.
FRONTIERS IN NEUROLOGY
(2022)
Review
Clinical Neurology
Arthur Stefanski, Yamile Calle-Lopez, Costin Leu, Eduardo Perez-Palma, Elia Pestana-Knight, Dennis Lal
Summary: This meta-analysis and systematic review examined the diagnostic yield of clinical sequencing studies in individuals with neurodevelopmental disorders, finding differences in success rates across NDD subtypes and sequencing technologies. Studies were predominantly conducted in countries with a high Inequality-adjusted Human Development Index, with potential barriers to genetic testing in regions like Africa, India, and Latin America.
Article
Pediatrics
Fiona M. Baumer, Nancy A. McNamara, Anthony L. Fine, Elia Pestana-Knight, Renee A. Shellhaas, Zihuai He, Daniel H. Arndt, William D. Gaillard, Sarah A. Kelley, Margot Nagan, Adam P. Ostendorf, Nilika S. Singhal, Laura Speltz, Kevin E. Chapman
Summary: In the US, benzodiazepines and antiseizure medications are the most common initial therapies prescribed for CSWS, but the study suggests that benzodiazepines and steroids are more effective than antiseizure medications. Treatment choice does not depend on baseline clinical variables, nor correlate with outcomes.
JOURNAL OF PEDIATRICS
(2021)
Article
Clinical Neurology
Jacinta Saldaris, Judith Weisenberg, Elia Pestana-Knight, Eric D. Marsh, Bernhard Suter, Rajsekar Rajaraman, Gena Heidary, Heather E. Olson, Orrin Devinsky, Dana Price, Peter Jacoby, Helen Leonard, Tim A. Benke, Scott Demarest, Jenny Downs
Summary: The content of the clinician-reported items in CCSA (CCSA-Clinician) was validated through interviews and consensus meetings with neurologists from the USA CDD Center of Excellence clinics. Eight original items were omitted, 11 items were added, and the remaining 18 items were revised. The final 29 items were classified into 2 domains: functioning and neurologic impairments, providing evidence for the content validity of CCSA-Clinician.
JOURNAL OF CHILD NEUROLOGY
(2021)
Article
Clinical Neurology
Heather E. Olson, Carolyn Daniels, Isabel Haviland, Lindsay C. Swanson, Caitlin A. Greene, Anne Marie M. Denny, Scott T. Demarest, Elia Pestana-Knight, Xiaoming Zhang, Ahsan N. Moosa, Andrea Fidell, Judith L. Weisenberg, Bernhard Suter, Cary Fu, Jeffrey L. Neul, Alan K. Percy, Eric D. Marsh, Timothy A. Benke, Annapurna Poduri
Summary: The treatment for neurological features of CDD is currently symptom-based and empirical, not specific to CDD. Anti-seizure medications are commonly used, with ketogenic diet also being a common treatment approach. There is limited information on medications for sleep, behavioral management, and movement disorders, highlighting the need for further research in these areas.
JOURNAL OF NEURODEVELOPMENTAL DISORDERS
(2021)
Article
Clinical Neurology
Helen Leonard, Mohammed Junaid, Kingsley Wong, Alex A. Aimetti, Elia Pestana Knight, Jenny Downs
Summary: This study found that patients with better early seizure control showed slightly improved development later, suggesting that an individual child's trajectory is not necessarily predetermined and could possibly be influenced by optimal seizure management. This has implications for children's quality of life.
Article
Clinical Neurology
Gozde Erdemir, Elia Pestana-Knight, Ryan Honomichl, Nicolas R. Thompson, Deepak Lachhwani, Prakash Kotagal, Elaine Wyllie, Ajay Gupta, William E. Bingaman, Ahsan N. Moosa
Summary: Surgery for drug-resistant epileptic spasms in children without intracranial EEG monitoring can achieve favorable outcomes, especially when epileptogenic lesions are identified on MRI. These findings suggest that surgery can be considered as a treatment option without the need for invasive monitoring in selected pediatric patients.
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.
Editorial Material
Clinical Neurology
Elia M. Pestana Knight
JOURNAL OF CLINICAL NEUROPHYSIOLOGY
(2022)
Review
Clinical Neurology
Elia M. Pestana Knight, Jayanti Mani
Summary: This article provides a historical review of knowledge developments about hypsarrhythmia and infantile spasms, with a focus on the period from 1952 to 1982. The goal is to highlight clinical elements that were discovered during that time and remain clinically relevant today.
JOURNAL OF CLINICAL NEUROPHYSIOLOGY
(2022)
Article
Clinical Neurology
Sam Amin, Marie Monaghan, Angel Aledo-Serrano, Nadia Bahi-Buisson, Richard F. Chin, Angus J. Clarke, J. Helen Cross, Scott Demarest, Orrin Devinsky, Jenny Downs, Elia M. Pestana Knight, Heather Olson, Carol-Anne Partridge, Graham Stuart, Marina Trivisano, Sameer Zuberi, Tim A. Benke
Summary: This article presents the characteristics, incidence, and impact of CDKL5 Deficiency Disorder (CDD), as well as recommendations from international healthcare professionals to address the diverse needs of individuals with CDD. Using a Delphi method, a consensus was reached and clinical management recommendations were proposed. These recommendations aim to standardize and improve the medical care for individuals with CDD.
FRONTIERS IN NEUROLOGY
(2022)
Article
Pediatrics
Swetha Padiyar, Neil Friedman, Elia Pestana-Knight, Ahsan Mossa-Naduvil, Linda Franic, Sarah Worley, Hany Aly
Summary: This study investigates the pre- and post-operative continuous EEG patterns in neonates with congenital heart disease, aiming to detect abnormal cerebral activity and explore the association between encephalopathy severity before and after surgery.
PEDIATRIC RESEARCH
(2023)
Article
Clinical Neurology
Ifrah Zawar, Linda Franic, Elia Pestana Knight
NEUROLOGY-CLINICAL PRACTICE
(2021)
Article
Clinical Neurology
Jessica R. Fesler, Anne E. Belcher, Ahsan N. Moosa, MaryAnn Mays, Lara E. Jehi, Elia M. Pestana Knight, Deepak K. Lachhwani, Andreas Alexopoulos, Dileep R. Nair, Vineet Punia
Summary: The study found that a pocket card is a beneficial educational tool for improving the implementation of treatment guidelines for status epilepticus. Teams with access to the pocket card had a shorter time to rescue therapy, while the presence of the card did not significantly impact the dosing adequacy. At the 9-month follow-up, most participants self-reported having the pocket card, but only a small portion could confirm the identification number.
NEUROLOGY-CLINICAL PRACTICE
(2021)
Article
Clinical Neurology
Elham Abushanab, Elia Pestana Knight, Ahsan N. Moosa
Summary: Children with a history of leukemia are at risk for drug-resistant epilepsy, with phenotypes including Lennox-Gastaut syndrome and focal epilepsy. Some patients show structural abnormalities on brain MRI, potentially contributing to the development of epilepsy.
EPILEPSY & BEHAVIOR REPORTS
(2021)
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)