Parkinson’s Disease in a Patient with 22q11.2 Deletion Syndrome: The Relevance of Detecting Mosaicisms by Means of Cell-By-Cell Evaluation Techniques

We report the case of a male patient from an Ashkenazi Jewish ethnic group with a history of midline defects (congenital heart disease, high-arched palate and bifid uvula). At the age of 46 years, he came to our center complaining of resting tremor, and a neurological examination concluded Parkinson?s disease. As a part of his approach, genetic evaluation was performed. Fluorescence in-situ hybridization (FISH) confirmed a mosaicism of a 22q deletion in 24% of the analyzed blood cells. Also, immunohistochemical studies were performed on samples from the minor salivary glands using a SNCA antibody. Intense SNCA immunoreactive profiles were obtained for cells from the salivary glands of the patient. This is, to our knowledge, the first description of the association of amosaicism of a 22q11.2 microdeletion syndrome with Parkinson?s disease. Our findings suggest that, before excluding the involvement of the 22q11.2 deletion in the etiology of early-onset PD cases, the spectrum of evaluations should be extended to include more sensitive FISH analysis and immunohistochemical studies. The pathogenesis of early-onset PD in patients with 22q11.2 deletion syndrome remains unknown but, if elucidated, it may contribute to understanding the etiology of PD and ultimately to preventionand treatment strategies.Fil: Perandones, Claudia. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; ArgentinaFil: Farini, Veronica Lujan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología. Centro de Estudios en Salud y Medio Ambiente; ArgentinaFil: Pellene, L. A. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Sáenz Farret, Michel. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Cuevas, S. M. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Micheli, Federico. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Radrizzani Helguera, Martin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología. Centro de Estudios en Salud y Medio Ambiente; Argentin

Generalized Dystonia and Paroxysmal Dystonic Attacks due to a Novel ATP1A3 Variant

Background: Paroxysmal movement disorders are a heterogeneous group of neurological diseases, better understood in recent years thanks to widely available genetic testing. Case report: A pair of monozygotic twins with dystonia and paroxysmal attacks, resembling paroxysmal non-kinesigenic dyskinesias, due to a novel ATP1A3 variant are reported. The complete resolution of their paroxysms was achieved using levodopa and deep brain stimulation of the internal globus pallidus. Improvement of interictal dystonia was also achieved with this therapy. Discussion: Paroxysmal worsening of movement disorders should be suspected as part of the ATP1A3 spectrum. Treatment outcome might be predicted based on the phenotype

Gerstmann-Sträussler-Scheinker syndrome in an Argentinean family due to mutationat codon 117 of the Prion Protein Gene (PrPA117V)

Prion Diseases or Transmissible Spongiform Encephalopathies (TSEs) constitute rare neurodegenerative diseases, the most common being Creutzfeldt–Jakob disease (CJD). Fifteen percent (15%) of the cases worldwide are considered to be of the familial type and the remainder (85%) present as a sporadic disorder (sCJD) [1]. The familial (or genetic) type includes: genetic CJD (gCJD), fatal familial insomnia (FFI), and Gerstmann–Sträussler–Scheinker syndrome (GSS) [2]. Here we present the clinical findings of an Argentinean family with GSS due to mutation at codon 117 of the prion protein gene (PrPA117V), the first in Argentina and in Latin America.Fil: Sáenz Farret, Michel. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Ramírez Gómez, Carolina Candelaria. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Aráoz Olivos, Natalia Silvana. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Carrillo Canedo, Heidi. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Aldinio, Victoria. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Montilla Uzcategui, Verónica Gisela. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Kauffman, Marcelo Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Micheli, Federico. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentin

Non- Motor Fluctuations in Parkinson’s Disease: Validation of the Non- Motor Fluctuation Assessment Questionnaire

BackgroundIn patients with Parkinson’s disease (PD), sleep, mood, cognitive, autonomic, and other non- motor symptoms may fluctuate in a manner similar to motor symptoms.ObjectivesTo validate a final version of a patient- rated questionnaire that captures the presence and severity of non- motor fluctuations in levodopa- treated PD patients (NoMoFA).MethodsWe recruited PD subjects from five movement disorders centers across the US and Canada. We assessed the internal consistency, floor and ceiling effects, test- retest reliability, and concurrent validity of NoMoFA. Classical test theory and item response theory methods informed item reduction and Delphi process yielded a final questionnaire.ResultsTwo hundred subjects and their care- partners participated in the study (age: 66.4- ±- 9.6- years; disease duration: 9- ±- 5.5- years; median Hoehn and Yahr [H&Y] OFF: 3 [range 1- 5]; mean Unified Parkinson’s Disease Rating Scale (UPDRS) III ON score: 27.4- ±- 14.9). Acceptability of the scale was adequate. There were floor effects in 8/28 items. Cronbach’s alpha was 0.894. While eight items had - item- to- total- correlations below the cutoff of 0.4, removing these items did not improve Cronbach’s alpha. Test- retest reliability was acceptable (intraclass correlation coefficient [ICC] 0.73; 95% confidence interval, 0.64- 0.80). Concurrent validity was adequate with all Spearman’s rho values comparing NoMoFA score to other measures of parkinsonian severity showing significance and in the expected direction. A final Delphi panel eliminated one item to avoid redundancy.ConclusionsThe final 27- item self- administered NoMoFA is a valid and reliable questionnaire, capturing both static and fluctuating non- motor symptoms in PD. © 2021 International Parkinson and Movement Disorder SocietyPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/168292/1/mds28507-sup-0001-Supinfo01.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/168292/2/mds28507_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/168292/3/mds28507-sup-0002-Supinfo02.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/168292/4/mds28507.pd