New diagnostic criteria for neurocysticercosis: Reliability and validity

Made available in DSpace on 2019-09-12T16:53:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2016Programa Iberoamericano de Ciencia y Tecnologia para el Desarrollo (CYTED)Department of Health's NIHR Biomedical Research Centres funding schemeDr. Marvin Weil Epilepsy Research FundObjectiveThe diagnosis of neurocysticercosis (NCC) remains problematic because of the heterogeneity of its clinical, immunological, and imaging characteristics. Our aim was to develop and assess a new set of diagnostic criteria for NCC, which might allow for the accurate detection of, and differentiation between, parenchymal and extraparenchymal disease. MethodsA group of Latin American NCC experts developed by consensus a new set of diagnostic criteria for NCC. A multicenter, retrospective study was then conducted to validate it. The reference standard for diagnosis of active NCC was the disappearance or reduction of cysts after anthelmintic treatment. In total, three pairs of independent neurologists blinded to the diagnosis evaluated 93 cases (with NCC) and 93 controls (without NCC) using the new diagnostic criteria. Mixed-effects logistic regression models were used to estimate sensitivity and specificity. ResultsInter-rater reliability (kappa) of diagnosis among evaluators was 0.60. For diagnosis of NCC versus no NCC, the new criteria had a sensitivity of 93.2% and specificity of 81.4%. For parenchymal NCC, the new criteria had a sensitivity of 89.8% and specificity of 80.7% and for extraparenchymal NCC, the new criteria had a sensitivity of 65.9% and specificity of 94.9%. InterpretationThese criteria have acceptable reliability and validity and could be a new tool for clinicians and researchers. An advantage of the new criteria is that they consider parasite location (ie, parenchymal or extraparenchymal), which is an important factor determining the clinical, immunological, and radiological presentation of the disease, and importantly, its treatment and prognosis. Ann Neurol 2016;80:434-442[Fleury, Agnes] Univ Nacl Autonoma Mexico, Inst Invest Biomed, Insurgentes Sur 3877, Mexico City 14269, DF, Mexico[Carpio, Arturo; Romo, Matthew L.] Univ Cuenca, Fac Ciencias Med, Cuenca, Ecuador[Carpio, Arturo] Columbia Univ, GH Sergievsky Ctr, New York, NY USA[Fleury, Agnes; Cardenas, Graciela; San-Juan, Daniel] Secretaria Salud Mexico, Inst Nacl Neurol & Neurocirugia, Mexico City, DF, Mexico[Romo, Matthew L.] CUNY, Grad Sch Publ Hlth & Hlth Policy, New York, NY 10021 USA[Abraham, Ronaldo] Universidade de Taubaté (Unitau), Sao Paulo, SP, Brazil[Fandino, Jaime] FIRE, Fdn Ctr Colombiano Epilepsia & Enfermedade Neurol, Cartagena, Colombia[Duran, Juan C.] Hosp Clin, Unidad Neurol, La Paz, Bolivia[Moncayo, Jorge] Univ Int Ecuador, Escuela Med, Quito, Ecuador[Rodrigues, Cleonisio Leite] Hosp Geral, Fortaleza, Ceara, Brazil[Serrano-Duenas, Marcos] Pontificia Univ Catolica Ecuador, Hosp Carlos Andrade Marin, Fac Med, Serv Neurol,IESS, Quito, Ecuador[Takayanagui, Oswaldo] Univ Sao Paulo, Fac Med, Ribeirao Preto, SP, Brazil[Sander, Josemir W.] UCL, Inst Neurol, NIHR Univ Coll London Hosp, Biomed Res Ctr, London, England[Sander, Josemir W.] SEIN, Heemstede, Netherland

Clinicogenetic lessons from 370 patients with autosomal recessive limb-girdle muscular dystrophy

Limb-girdle muscular dystrophies (LGMD) are a group of genetically heterogeneous disorders characterized by predominantly proximal muscle weakness. We aimed to characterize epidemiological, clinical and molecular data of patients with autosomal recessive LGMD2/LGMD-R in Brazil. A multicenter historical cohort study was performed at 13 centers, in which index cases and their affected relatives' data from consecutive families with genetic or pathological diagnosis of LGMD2/LGMD-R were reviewed from July 2017 to August 2018. Survival curves to major handicap for LGMD2A/LGMD-R1-calpain3-related, LGMD2B/LGMD-R2-dysferlin-related and sarcoglycanopathies were built and progressions according to sex and genotype were estimated. In 370 patients (305 families) with LGMD2/LGMD-R, most frequent subtypes were LGMD2A/LGMD-R1-calpain3-related and LGMD2B/LGMD-R2-dysferlin-related, each representing around 30% of families. Sarcoglycanopathies were the most frequent childhood-onset subtype, representing 21% of families. Five percent of families had LGMD2G/LGMD-R7-telethonin-related, an ultra-rare subtype worldwide. Females with LGMD2B/LGMD-R2-dysferlin-related had less severe progression to handicap than males and LGMD2A/LGMD-R1-calpain3-related patients with truncating variants had earlier disease onset and more severe progression to handicap than patients without truncating variants. We have provided paramount epidemiological data of LGMD2/LGMD-R in Brazil that might help on differential diagnosis, better patient care and guiding future collaborative clinical trials and natural history studies in the field964341353The authors are grateful to patients and their families for participationin this study and professionals who also attended these individuals,but were not directly involved in this research project. We also thankSanofi-Genzyme who supported genetic diagnosis investigations atsome centers. The study was funded by Fundo de Incentivo à Pes-quisa e Eventos-HCPA (Grant Number: 17-0340) and by researchgrant from PTC-Therapeutics. Bená MI received support fromConselho Nacional de Desenvolvimento Cientifico e Tecnológico(Grant Number: 134351/2015-0