- Browse by Subject
Browsing by Subject "Dyskinesias"
Now showing 1 - 3 of 3
Results Per Page
Sort Options
Item Boricua Founder Variant in FRRS1L Causes Epileptic Encephalopathy With Hyperkinetic Movements(Sage, 2021) Abdelmoumen, Imane; Jimenez, Sandra; Valencia, Ignacio; Melvin, Joseph; Legido, Agustin; Diaz-Diaz, Mayela M.; Griffith, Christopher; Massingham, Lauren J.; Yelton, Melissa; Rodríguez-Hernández, Janice; Schnur, Rhonda E.; Walsh, Laurence E.; Cristancho, Ana G.; Bergqvist, Christina A.; McWalter, Kirsty; Mathieson, Iain; Belbin, Gillian M.; Kenny, Eimear E.; Ortiz-Gonzalez, Xilma R.; Schneider, Michael C.; Neurology, School of MedicineObjective: To describe a founder mutation effect and the clinical phenotype of homozygous FRRS1L c.737_739delGAG (p.Gly246del) variant in 15 children of Puerto Rican (Boricua) ancestry presenting with early infantile epileptic encephalopathy (EIEE-37) with prominent movement disorder. Background: EIEE-37 is caused by biallelic loss of function variants in the FRRS1L gene, which is critical for AMPA-receptor function, resulting in intractable epilepsy and dyskinesia. Methods: A retrospective, multicenter chart review of patients sharing the same homozygous FRRS1L (p.Gly246del) pathogenic variant identified by clinical genetic testing. Clinical information was collected regarding neurodevelopmental outcomes, neuroimaging, electrographic features and clinical response to antiseizure medications. Results: Fifteen patients from 12 different families of Puerto Rican ancestry were homozygous for the FRRS1L (p.Gly246del) pathogenic variant, with ages ranging from 1 to 25 years. The onset of seizures was from 6 to 24 months. All had hypotonia, severe global developmental delay, and most had hyperkinetic involuntary movements. Developmental regression during the first year of life was common (86%). Electroencephalogram showed hypsarrhythmia in 66% (10/15), with many older children evolving into Lennox-Gastaut syndrome. Six patients demonstrated progressive volume loss and/or cerebellar atrophy on brain magnetic resonance imaging (MRI). Conclusions: We describe the largest cohort to date of patients with epileptic encephalopathy. We estimate that 0.76% of unaffected individuals of Puerto Rican ancestry carry this pathogenic variant due to a founder effect. Children homozygous for the FRRS1L (p.Gly246del) Boricua variant exhibit a very homogenous phenotype of early developmental regression and epilepsy, starting with infantile spasms and evolving into Lennox-Gastaut syndrome with hyperkinetic movement disorder.Item Differences in the Presentation and Progression of Parkinson's Disease by Sex(Wiley, 2021) Iwaki, Hirotaka; Blauwendraat, Cornelis; Leonard, Hampton L.; Makarious, Mary B.; Kim, Jonggeol J.; Liu, Ganqiang; Maple-Grødem, Jodie; Corvol, Jean-Christophe; Pihlstrøm, Lasse; van Nimwegen, Marlies; Smolensky, Luba; Amondikar, Ninad; Hutten, Samantha J.; Frasier, Mark; Nguyen, Khanh-Dung H.; Rick, Jacqueline; Eberly, Shirley; Faghri, Faraz; Auinger, Peggy; Scott, Kirsten M.; Wijeyekoon, Ruwani; Van Deerlin, Vivianna M.; Hernandez, Dena G.; Gibbs, Raphael J.; Day-Williams, Aaron G.; Brice, Alexis; Alves, Guido; Noyce, Alastair J.; Tysnes, Ole-Bjørn; Evans, Jonathan R.; Breen, David P.; Estrada, Karol; Wegel, Claire E.; Danjou, Fabrice; Simon, David K.; Andreassen, Ole A.; Ravina, Bernard; Toft, Mathias; Heutink, Peter; Bloem, Bastiaan R.; Weintraub, Daniel; Barker, Roger A.; Williams-Gray, Caroline H.; van de Warrenburg, Bart P.; Van Hilten, Jacobus J.; Scherzer, Clemens R.; Singleton, Andrew B.; Nalls, Mike A.; Medical and Molecular Genetics, School of MedicineBackground: Previous studies reported various symptoms of Parkinson's disease (PD) associated with sex. Some were conflicting or confirmed in only one study. Objectives: We examined sex associations to PD phenotypes cross-sectionally and longitudinally in large-scale data. Methods: We tested 40 clinical phenotypes, using longitudinal, clinic-based patient cohorts, consisting of 5946 patients, with a median follow-up of 3.1 years. For continuous outcomes, we used linear regressions at baseline to test sex-associated differences in presentation, and linear mixed-effects models to test sex-associated differences in progression. For binomial outcomes, we used logistic regression models at baseline and Cox regression models for survival analyses. We adjusted for age, disease duration, and medication use. In the secondary analyses, data from 17 719 PD patients and 7588 non-PD participants from an online-only, self-assessment PD cohort were cross-sectionally evaluated to determine whether the sex-associated differences identified in the primary analyses were consistent and unique to PD. Results: Female PD patients had a higher risk of developing dyskinesia early during the follow-up period, with a slower progression in activities of daily living difficulties, and a lower risk of developing cognitive impairments compared with male patients. The findings in the longitudinal, clinic-based cohorts were mostly consistent with the results of the online-only cohort. Conclusions: We observed sex-associated contributions to PD heterogeneity. These results highlight the necessity of future research to determine the underlying mechanisms and importance of personalized clinical management.Item Tremor as a symptom of degenerative cervical myelopathy: a systematic review(Taylor & Francis, 2022) El Khoury, Marc; Mowforth, Oliver D.; El Khoury, Anthony; Partha-Sarathi, Celine; Hirayama, Yuri; Davies, Benjamin M.; Kotter, Mark R.; Medicine, School of MedicineBackground: AO Spine RECODE-DCM (Research objectives and common data elements for degenerative cervical myelopathy) has highlighted that the subjective disability reported by people living with DCM is much broader than routinely considered today by most professionals. This includes a description of tremor. The objective of this review was to study the incidence and possible aetiology of tremor in degenerative cervical myelopathy (DCM). Methods: A systematic review registered in PROSPERO (CRD42020176905) was conducted in Embase and MEDLINE for papers studying tremor and DCM published on or before the 20th of July 2020. All manuscripts describing an association between tremor and DCM in humans were included. Articles relating to non-human animals, and those not available in English were excluded. An analysis was conducted in accordance with PRISMA and SWiM guidelines for systematic reviews. Results: Out of a total of 4402 screened abstracts, we identified 7 case reports and series describing tremor in 9 DCM patients. Papers were divided into three groups for the discussion. The first group includes DCM correctly identified on presentation, with tremor as a described symptom. The second group includes cases where DCM was misdiagnosed, often as Parkinson's disease. The third group includes a single case with a previous history of DCM, presenting with an otherwise unexplained tremor. This grouping allows for the clustering of cases supporting various arguments for the association between tremor and DCM. Conclusion: DCM can be associated with tremor. The current evidence is restricted to case series. Further study is warranted to establish tremor prevalence, and its significance to assessment and management.