Congenital myopathies: Clinical phenotypes and new diagnostic tools

Congenital myopathies are a group of genetic muscle disorders characterized clinically by hypotonia and weakness, usually from birth, and a static or slowly progressive clinical course. Historically, congenital myopathies have been classified on the basis of major morphological features seen on muscle biopsy. However, different genes have now been identified as associated with the various phenotypic and histological expressions of these disorders, and in recent years, because of their unexpectedly wide genetic and clinical heterogeneity, next-generation sequencing has increasingly been used for their diagnosis. We reviewed clinical and genetic forms of congenital myopathy and defined possible strategies to improve cost-effectiveness in histological and imaging diagnosis

Lipoprotein(a) Genotype Influences the Clinical Diagnosis of Familial Hypercholesterolemia

: Background Evidence suggests that LPA risk genotypes are a possible contributor to the clinical diagnosis of familial hypercholesterolemia (FH). This study aimed at determining the prevalence of LPA risk variants in adult individuals with FH enrolled in the Italian LIPIGEN (Lipid Transport Disorders Italian Genetic Network) study, with (FH/M+) or without (FH/M-) a causative genetic variant. Methods and Results An lp(a) [lipoprotein(a)] genetic score was calculated by summing the number risk-increasing alleles inherited at rs3798220 and rs10455872 variants. Overall, in the 4.6% of 1695 patients with clinically diagnosed FH, the phenotype was not explained by a monogenic or polygenic cause but by genotype associated with high lp(a) levels. Among 765 subjects with FH/M- and 930 subjects with FH/M+, 133 (17.4%) and 95 (10.2%) were characterized by 1 copy of either rs10455872 or rs3798220 or 2 copies of either rs10455872 or rs3798220 (lp(a) score ≥1). Subjects with FH/M- also had lower mean levels of pretreatment low-density lipoprotein cholesterol than individuals with FH/M+ (t test for difference in means between FH/M- and FH/M+ groups <0.0001); however, subjects with FH/M- and lp(a) score ≥1 had higher mean (SD) pretreatment low-density lipoprotein cholesterol levels (223.47 [50.40] mg/dL) compared with subjects with FH/M- and lp(a) score=0 (219.38 [54.54] mg/dL for), although not statistically significant. The adjustment of low-density lipoprotein cholesterol levels based on lp(a) concentration reduced from 68% to 42% the proportion of subjects with low-density lipoprotein cholesterol level ≥190 mg/dL (or from 68% to 50%, considering a more conservative formula). Conclusions Our study supports the importance of measuring lp(a) to perform the diagnosis of FH appropriately and to exclude that the observed phenotype is driven by elevated levels of lp(a) before performing the genetic test for FH

COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context

Background and objectives: It is unclear how multiple sclerosis (MS) affects the severity of COVID-19. The aim of this study is to compare COVID-19-related outcomes collected in an Italian cohort of patients with MS with the outcomes expected in the age- and sex-matched Italian population. Methods: Hospitalization, intensive care unit (ICU) admission, and death after COVID-19 diagnosis of 1,362 patients with MS were compared with the age- and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher risk: Expanded Disability Status Scale [EDSS] score > 3 or at least 1 comorbidity, lower risk: EDSS score ≤ 3 and no comorbidities) by the χ2 test, and the risk excess was quantified by risk ratios (RRs). Results: The risk of severe events was about twice the risk in the age- and sex-matched Italian population: RR = 2.12 for hospitalization (p < 0.001), RR = 2.19 for ICU admission (p < 0.001), and RR = 2.43 for death (p < 0.001). The excess of risk was confined to the higher-risk group (n = 553). In lower-risk patients (n = 809), the rate of events was close to that of the Italian age- and sex-matched population (RR = 1.12 for hospitalization, RR = 1.52 for ICU admission, and RR = 1.19 for death). In the lower-risk group, an increased hospitalization risk was detected in patients on anti-CD20 (RR = 3.03, p = 0.005), whereas a decrease was detected in patients on interferon (0 observed vs 4 expected events, p = 0.04). Discussion: Overall, the MS cohort had a risk of severe events that is twice the risk than the age- and sex-matched Italian population. This excess of risk is mainly explained by the EDSS score and comorbidities, whereas a residual increase of hospitalization risk was observed in patients on anti-CD20 therapies and a decrease in people on interferon

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

Efeitos cardiovasculares da apomorfina, um agonista dopaminérgico D1/D2, em ratos hipertensos Doca-Sal, acordados : estudo do mecanismo de ação

Este estudo investiga os efeitos da apomorfina (APO) sobre a pressão arterial e o principal sítio de ação deste agonista em ratos hipertensos, após tratamento durante quatro semanas com acetato de deoxicorticosterona (DOCA), acordados. A administração intravenosa (i.v.) de APO (0,50-1 mg/Kg) produziu uma redução da pressão arterial média de curta duração e dosedependente. A magnitude desta resposta foi similar em ratos normotensos uninefrectomizados. Em ratos hipertensos DOCA-sal, a resposta hipotensora para APO (0,3 mg/Kg) não foi modificada pelo pré-tratamento i.v. com metil-atropina (1 mg/Kg) ou propranolol (2 mg/Kg), mas foi revertida em um efeito pressor significativo, com o uso de hexametônio (30 mg/Kg, i.v.), sendo amplificada pelo pré-tratamento i.v. com d(CH2)5Tyr(Me)arginina vasopressina (AVP) (10 mg/Kg) e/ou prazosina (1 mg/Kg). O efeito depressor da APO foi suprimido pela metoclopramida (5 mg/Kg, i.v.), não foi alterado pelo SCH 23390 (0,2 mg/Kg, i.v.), foi parcialmente reduzido pela domperidona intratecal (40 μg/rato a nível T9-T10), e revertido em um efeito pressor significativo pela pré-tratamento i.v. com domperidona (0,5 mg/Kg). Este último efeito pressor foi maior do que nos ratos normotensos controles, sendo parcialmente reduzido pelo antagonista do AVP (10 mg/Kg, i.v.), e totalmente abolido pela combinação do pré-tratamento i.v. com o antagonista da AVP e prazosina. Em resumo, estes resultados mostram que, em ratos DOCA-sal acordados, a APO induz um efeito inicial depressor, breve, que se opõe ao componente pressor central. O componente depressor esta relacionado a inibição da noradrenalina liberada das terminações nervosas através da ativação de receptores D2, alguns dos quais localizados na medula espinhal e alguns na circulação periférica. O componente pressor central manifesta-se após o bloqueio dos receptores dopaminérgicos D2 periféricos, e parece estar relacionado ao aumento da liberação de AVP e do tônus simpático através da ativação dos receptores dopaminérgicos D2 cerebrai

PERFIL EPIDEMIOLÓGICO DE SUJEITOS COM DISFUNÇÃO TEMPOROMANDIBULAR TRATADOS NA FACULDADE DE ODONTOLOGIA DE CARUARU PERNAMBUCO

A articulação temporomandibular (ATM) é constituída pela fossa mandibular do osso temporal e côndilo da mandíbula. Ela é responsável pela movimentação da mandíbula durante a mastigação, deglutição e conversação. Entretanto, o excesso de uso e a perda de harmonia de seus constituintes articulares e musculares predispõem ao aparecimento da Disfunção Temporomandibular (DTM). Essa disfunção apresenta uma etiologia multifatorial com complexidade de sinais e sintomas que dificultam seu diagnóstico. Este estudo teve por objetivo traçar o perfil epidemiológico dos sujeitos com DTM, tratados na Faculdade de Odontologia de Caruaru Pernambuco. Foram coletados dados de 53 prontuários de sujeitos com DTM e as variáveis seguintes analisadas: sexo, idade, abertura bucal, ausculta, presença de dores no ouvido, região cervical e cefaléia, dor muscular e hábitos gerais. Os resultados mostraram que a DTM acometeu em maior percentual o sexo feminino, na faixa etária entre 28 e 39 anos. Cerca de 41,5% dos sujeitos referiram estalidos durante os movimentos da ATM. O bruxismo estava presente em 28,3% dos sujeitos. E os dados em relação à dor mostraram que 75,5% dos sujeitos referiram dor cervical, 71,1% cefaléia associada e 28,3% referiram dor no músculo masseter. Esta pesquisa mostrou que os principais fatores envolvidos nas DTMs seguem o padrão da literatura que trata do assunto

Targeted Audiological Surveillance Program in Campania, Italy

To identify children with postnatal hearing loss, a structured monitoring system is needed. The goal of this study was to describe a targeted surveillance program in Italy to identify children with postnatal hearing loss

Postural Evaluation of Vertebral Column in Children and Teenagers with Hearing Loss

Introduction: Posture is determined by the performance of the visual, somatosensory and vestibular systems. Children with hearing loss can present problems in their posture or postural control, enabling postural deviations and alterations to appear in their vertebral column, possibly provoked by a hypoactivity of the vestibular system as a result of deafness. Objective: To evaluate the posture of the vertebral column in children and teenagers with hearing loss at school age, taking into consideration the sample gender and age. Method: A descriptive and prospective study was performed at both Duque de Caxias School and Rotary Rehabilitation and Special Education Center in Caruaru - Pernambuco. 44 students aged between 7-17 years old, out of whom 22 were female and 22 were male, with hearing loss were evaluated. The study was developed by way of a postural evaluation, using a symmetrograph, marking specific anatomical points with stickers placed over polystyrene balls and fixed with double-sided adhesive tape. Results:The results showed that all of the individuals evaluated in this study presented some kind of postural alteration in their vertebral column. Scoliosis was the most observed alteration among the students (84.1%), followed by thoracic hyperkyphosis (68.2%). Conclusion: It has been concluded that children and teenagers with hearing loss are exposed to postural alteration in their vertebral column. Such a condition can be associated with a number of factors comprising unfavorable ergonomics of the school environment, bad postural habits and impairment of the vestibular system by virtue of the hearing loss

Postural control assessment in students with normal hearing and sensorineural hearing loss

INTRODUCTION: Children with sensorineural hearing loss can present with instabilities in postural control, possibly as a consequence of hypoactivity of their vestibular system due to internal ear injury.OBJECTIVE: To assess postural control stability in students with normal hearing (i.e., listeners) and with sensorineural hearing loss, and to compare data between groups, considering gender and age.METHODS: This cross-sectional study evaluated the postural control of 96 students, 48 listeners and 48 with sensorineural hearing loss, aged between 7 and 18 years, of both genders, through the Balance Error Scoring Systems scale. This tool assesses postural control in two sensory conditions: stable surface and unstable surface. For statistical data analysis between groups, the Wilcoxon test for paired samples was used.RESULTS: Students with hearing loss showed more instability in postural control than those with normal hearing, with significant differences between groups (stable surface, unstable surface) (p < 0.001).CONCLUSIONS: Students with sensorineural hearing loss showed greater instability in the postural control compared to normal hearing students of the same gender and age