Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.621
Filtrar
1.
Rev Neurol (Paris) ; 176(6): 507-515, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32354651

RESUMEN

In France, the epidemic phase of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in February 2020 and resulted in the implementation of emergency measures and a degradation in the organization of neuromuscular reference centers. In this special context, the French Rare Health Care for Neuromuscular Diseases Network (FILNEMUS) has established guidance in an attempt to homogenize the management of neuromuscular (NM) patients within the French territory. Hospitalization should be reserved for emergencies, the conduct of treatments that cannot be postponed, check-ups for which the diagnostic delay may result in a loss of survival chance, and cardiorespiratory assessments for which the delay could be detrimental to the patient. A national strategy was adopted during a period of 1 to 2months concerning treatments usually administered in hospitalization. NM patients treated with steroid/immunosuppressants for a dysimmune pathology should continue all of their treatments in the absence of any manifestations suggestive of COVID-19. A frequently asked questions (FAQ) sheet has been compiled and updated on the FILNEMUS website. Various support systems for self-rehabilitation and guided exercises have been also provided on the website. In the context of NM diseases, particular attention must be paid to two experimental COVID-19 treatments, hydroxycholoroquine and azithromycin: risk of exacerbation of myasthenia gravis and QT prolongation in patients with pre-existing cardiac involvement. The unfavorable emergency context related to COVID-19 may specially affect the potential for intensive care admission (ICU) for people with NMD. In order to preserve the fairest medical decision, a multidisciplinary working group has listed the neuromuscular diseases with a good prognosis, usually eligible for resuscitation admission in ICU and, for other NM conditions, the positive criteria suggesting a good prognosis. Adaptation of the use of noninvasive ventilation (NIV) make it possible to limit nebulization and continue using NIV in ventilator-dependent patients.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/epidemiología , Enfermedades Neuromusculares/terapia , Pandemias , Neumonía Viral/epidemiología , Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antibacterianos/uso terapéutico , Antimaláricos/uso terapéutico , Azitromicina/uso terapéutico , Capacidad Cardiovascular , Infecciones por Coronavirus/tratamiento farmacológico , Tratamiento de Urgencia , Francia/epidemiología , Enfermedad del Almacenamiento de Glucógeno Tipo II/terapia , Hospitalización , Humanos , Hidroxicloroquina/uso terapéutico , Enfermedades del Sistema Inmune/terapia , Inmunoglobulinas Intravenosas/uso terapéutico , Inmunosupresores/uso terapéutico , Atrofia Muscular Espinal/tratamiento farmacológico , Oligonucleótidos/uso terapéutico , Modalidades de Fisioterapia , Neumonía Viral/tratamiento farmacológico , Pronóstico , ARN Interferente Pequeño/uso terapéutico , Esteroides/uso terapéutico , Privación de Tratamiento , alfa-Glucosidasas/uso terapéutico
2.
Muscle Nerve ; 62(1): 46-49, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32329921

RESUMEN

The coronavirus disease 2019 (COVID-19) pandemic has resulted in reorganization of healthcare settings affecting the delivery of clinical care to patients with spinal muscular atrophy (SMA). There is a concern that patients with SMA may be at increased risk of manifesting severe symptoms of COVID-19. Currently approved therapies for SMA improve survival and motor function; however, their delivery requires an increased exposure to the health system and a dedicated healthcare team. In this study, we discuss consensus recommendations pertaining to care of SMA patients during the pandemic. We highlight that SMA treatments should not be perceived as elective. Decisions regarding the delay of treatments should be made with consideration of the potential risks of COVID-19 exposure and the risk of that delay. We emphasize the importance of collaborative treatment decisions between the patient, family, and healthcare provider, considering any geographic- or institution-specific policies and precautions for COVID-19.


Asunto(s)
Betacoronavirus , Consenso , Infecciones por Coronavirus/complicaciones , Prestación de Atención de Salud/métodos , Manejo de la Enfermedad , Atrofia Muscular Espinal/terapia , Pandemias , Neumonía Viral/complicaciones , Infecciones por Coronavirus/epidemiología , Humanos , Atrofia Muscular Espinal/complicaciones , Neumonía Viral/epidemiología
3.
Zhonghua Er Ke Za Zhi ; 58(4): 308-313, 2020 Apr 02.
Artículo en Chino | MEDLINE | ID: mdl-32234138

RESUMEN

Objective: To investigate the coverage rate and the adverse reactions of National Immunization Program vaccines in children with spinal muscular atrophy (SMA). Methods: A cross-sectional retrospective cohort study was carried out from July 2016 to June 2019, 192 children (116 boys and 76 girls) with SMA registered by Capital Institute of Pediatrics and 191 healthy children (115 boys and 76 girls) vaccinated in Chaoyang Olympic Village Community Health Service Center from July 2016 to December 2018 were included. Questionnaire survey was designed to investigate the vaccination coverage rate and associated adverse events. The t-test and χ(2) test were used to compare the difference between SMA patients and healthy children. Results: The coverage rate of age-appropriate immunization in SMA children was 62.0% (119/192) in general, and were 52.2% (12/23), 55.7% (68/122), and 83.0% (39/47) for SMA type 1-3 patients, respectively (χ(2)=12.23, P=0.002). The vaccination coverage rates of Bacillus Calmette-Guerin (BCG) vaccine, the 3(rd) dose of hepatitis B, the 3(rd) dose of polio, the 3(rd) dose of diphtheria-pertussis-tetanus, the 1(st) dose of meningococcal polysaccharide group A, the 1(st) dose of measles or measles and rubella vaccine, the 1(st) dose of Japanese encephalitis vaccine, hepatitis A, measles-mumps-rubella, and group A+C meningococcal polysaccharide vaccine were 100.0% (192 cases), 94.3% (181 cases), 81.8% (157 cases), 88.5% (170 cases), 83.9% (161 cases), 76.6% (147 cases), 80.2% (154 cases), 68.2% (131 cases), 69.8% (134 cases), 54.7% (105 cases), respectively. Among the 73 patients who did not have their planned immunization completed, 57 cases (78.1%) gave up the vaccination due to parents' concern of potential aggravation of their disease, and 16 cases (21.9%) had the plan discontinued by the immunization department because of the disease. Fever, local redness and swelling were the most common side-effects after vaccination both in SMA patients and healthy children (19.8% (38/192) vs. 18.8% (36/191) , χ(2)=0.055, P=0.815). The main abnormal reactions of vaccination were rash and neurovascular edema, without significant difference between these two groups (2.6% (5/192) vs. 3.7% (7/191), χ(2)=0.355, P=0.551). The coverage rate of Influenza and pneumococcal vaccine in SMA patients were 22.4% (43 cases) and 31.8% (61 cases), respectively. The incidence of pneumonia in the SMA patients decreased from 59.0% (23/39) to 41.0% (16/39) after vaccination. And none of the Influenza vaccinated patients had the flu in the year of vaccination. Conclusions: The coverage rate of National Immunization Program vaccines in the SMA children is low, especially in type 1 SMA patients, which is mainly due to their guardians' concern of potential adverse events, even though the incidence of adverse reactions is similar in SMA patients and healthy children. Influenza and pneumococcal vaccine can reduce the risk of pneumonia and flu in children with SMA effectively.


Asunto(s)
Programas de Inmunización , Atrofia Muscular Espinal , Vacunación/estadística & datos numéricos , Vacunas/efectos adversos , Niño , China , Estudios Transversales , Femenino , Humanos , Masculino , Estudios Retrospectivos
4.
Yonsei Med J ; 61(4): 273-283, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32233169

RESUMEN

The reduction of survival motor neuron (SMN) protein causes spinal muscular atrophy (SMA), an autosomal recessive neuromuscular disease. Nusinersen is an antisense oligonucleotide, approved by the FDA, which specifically binds to the repressor within SMN2 exon 7 to enhance exon 7 inclusion and augment production of functional SMN protein. Nusinersen is the first new oligonucleotide-based drug targeting the central nervous system for the treatment of SMA. This review of nusinersen will discuss its action mechanism, cellular uptake, trafficking mechanisms, and administration approaches to cross the blood-brain barrier. Furthermore, nusinersen clinical trials will be assessed in terms of pharmacokinetics, tolerability and safety, the clinical outcomes of multiple intrathecal doses, and a discussion on the primary and secondary endpoints.


Asunto(s)
Exones/genética , Atrofia Muscular Espinal/terapia , Oligonucleótidos Antisentido/uso terapéutico , Oligonucleótidos/uso terapéutico , Barrera Hematoencefálica , Humanos , Atrofia Muscular Espinal/genética
5.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(4): 384-388, 2020 Apr 10.
Artículo en Chino | MEDLINE | ID: mdl-32219818

RESUMEN

OBJECTIVE: To perform carrier screening for spinal muscular atrophy (SMA) among 3049 reproductive-age individuals from Yunnan region and determine the copy number of survival motor neuron (SMN) gene and carrier frequencies. METHODS: Multiplex ligation-dependent probe amplification (MLPA) was used to determine the copy number of exon 7 of SMN1 and SMN2 genes and identify those with a single copy of SMN1 gene. Prenatal diagnosis was performed for couples whom were both found to be SMA carriers. RESULTS: In total 62 SMA carriers were identified among the 3049 subjects, which yielded a carrier frequency of 1 in 49 (2.03%). No statistical difference was found in the carrier frequency between males and females (1.91% vs. 2.30%, P>0.05). Respectively, 1.3% (41/3049) and 0.69% (21/3049) of the carriers were caused by heterozygous deletion and conversion of the SMN1 gene. The average copy number for SMN1 alleles was 1.99. Two couples were found to be both as SMA carriers, for whom the birth of an affected fetus was avoided by prenatal diagnosis. CONCLUSION: No difference was found in the carrier frequency of SMA-related mutations between the two genders in Yunnan region, which was in keeping to an autosomal recessive inheritance pattern. Determination of the carrier frequency for SMA and SMN gene variants may provide a basis for genetic counseling and prenatal diagnosis for the disease.


Asunto(s)
Tamización de Portadores Genéticos , Atrofia Muscular Espinal/genética , Proteína 1 para la Supervivencia de la Neurona Motora/genética , China , Femenino , Asesoramiento Genético , Variación Genética , Heterocigoto , Humanos , Masculino , Embarazo , Diagnóstico Prenatal , Proteína 2 para la Supervivencia de la Neurona Motora/genética
6.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(3): 263-268, 2020 Mar 10.
Artículo en Chino | MEDLINE | ID: mdl-32128742

RESUMEN

Spinal muscular atrophy (SMA) is one of the most common fatal autosomal recessive genetic disorders among infants. It is caused by mutations of motor neuron survival gene 1 (SMN1). The incidence of SMA among newborns is approximately 1/10 000 - 1/6000, and the carrier rate is 1/72 - 1/47 with an ethnic variance. Based on the time of onset and clinical phenotype, SMA can be divided into types I - IV. Approximately 95% of SMA patients have carried homozygous deletions of exon 7 of the (SMN1)] gene. For its significant phenotypic difference, abundant changes of (SMN1)] gene copy number, presence of pseudogene interference and high carrier rate, early diagnosis, genetic consultation, treatment and prevention of SMA can be difficult. This guideline summarizes the relevant research, guideline and consensus issued at home and abroad, clinical manifestations and pathogenesis of SMA patients, and experience in its diagnosis and genetic counseling, with an aim to promote a standardized diagnosis and treatment and reduce the births of children affected with the disease.


Asunto(s)
Atrofia Muscular Espinal/diagnóstico , Atrofia Muscular Espinal/terapia , Guías de Práctica Clínica como Asunto , Exones , Dosificación de Gen , Asesoramiento Genético , Heterocigoto , Humanos , Recién Nacido , Fenotipo , Eliminación de Secuencia , Proteína 1 para la Supervivencia de la Neurona Motora/genética
7.
Am J Occup Ther ; 74(2): 7402205080p1-7402205080p10, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32204786

RESUMEN

IMPORTANCE: People with Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA) develop impaired oral function because of reduced temporomandibular joint range of motion (ROM), which affects feeding and oral hygiene activities of daily living (ADLs). OBJECTIVE: To assess whether the TheraBite®, an intraoral stretching device, improves ROM. DESIGN: Case series, with intervention duration varying from 7 to 30 mo. Treatment frequency varied from weekly to consultative (several times per year). SETTING: Varied depending on the ease of transportation for the participant and caregivers. Two participants were treated in an outpatient medical clinic. The other was provided consultative care during multidisciplinary medical clinics and completed a home program. PARTICIPANTS: Two adults with DMD and one with SMA. INTERVENTION: Stretching protocol using the TheraBite. OUTCOMES AND MEASURES: Temporomandibular active ROM (AROM) was determined using a disposable TheraBite oral goniometer. Passive ROM (PROM) was determined using the adhesive scale on the TheraBite. Measures were taken at baseline, each intervention or consultation, and the end of care. ADL participation and caregiver burden were measured at the end of intervention. RESULTS: For participants with DMD, AROM remained unchanged, but PROM increased by 40%-65%. The participant with SMA demonstrated 33% and 47% improvements in AROM and PROM, respectively. Participants or caregivers reported improved feeding function, improved oral hygiene, or reduced fatigue. CONCLUSION: TheraBite may improve temporomandibular PROM in people with DMD and temporomandibular AROM and PROM in people with SMA. It may also improve ADL function and consequently reduce caregiver burden. Further investigation is warranted. WHAT THIS ARTICLE ADDS: Temporomandibular contracture in people with DMD and SMA contributes to reduced lifespan and loss of function. Use of the TheraBite with this population may preserve temporomandibular ROM and improve feeding, hygiene, and quality-of-life outcomes.


Asunto(s)
Atrofia Muscular Espinal , Distrofia Muscular de Duchenne , Actividades Cotidianas , Adulto , Humanos , Atrofia Muscular Espinal/fisiopatología , Distrofia Muscular de Duchenne/fisiopatología , Calidad de Vida , Rango del Movimiento Articular
8.
PLoS One ; 15(3): e0230677, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32203538

RESUMEN

BACKGROUND: The advent of new therapies has increased the need to achieve early diagnosis in Spinal Muscular Atrophy (SMA). The aim of the present study was to define the age of diagnosis in the three main types of SMA with pediatric-onset and the timing between the recognition of clinical signs and confirmed genetic diagnosis. METHODS: All patients with a confirmed diagnosis of type I, II, III SMA followed in 5 Italian centers were included in this study, assessing age at symptoms onset, presenting sign or symptom, age at diagnosis, interval between clinical onset and diagnosis and type of medical investigations conducted in order to obtain the diagnosis. RESULTS: The cohort included 480 patients, 191 affected by SMA type I, 210 by type II and 79 by type III. The mean age at diagnosis was 4.70 months (SD ±2.82) in type I, 15.6 months (SD±5.88) in type II, and 4.34 years (SD±4.01) in type III. The mean time between symptom onset and diagnosis was 1.94 months (SD±1.84) in type I, 5.28 months (SD±4.68) in type II and 16.8 months (SD±18.72) in type III. CONCLUSIONS: Our results suggest that despite improved care recommendations there is still a marked diagnostic delay, especially in type III. At the time new therapies are becoming available more attention should be devoted to reducing such delay as there is consistent evidence of the benefit of early treatment.


Asunto(s)
Atrofia Muscular Espinal/diagnóstico , Edad de Inicio , Estudios de Cohortes , Femenino , Humanos , Lactante , Masculino , Atrofia Muscular Espinal/genética
10.
Medicine (Baltimore) ; 99(5): e18975, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32000428

RESUMEN

INTRODUCTION: Spinal muscular atrophy (SMA) was the second most fatal autosomal recessive hereditary disease in clinic. There had been no detailed study to characterize the prevalence of SMA carrier among people in China. So, we conducted a systematic review and meta-analysis to obtain a reliable estimation of the prevalence of SMA carrier to characterize its epidemiology for the first time. METHODS: We systematically searched for articles in kinds of important electronic databases, including PubMed, Embase, Wanfang Database and China National Knowledge Infrastructure (CNKI) to identify all relevant literatures about carrier rates of SMA in China. The prevalence was performed by forest plot choosing random effect models. The publication bias was evaluated by means of funnel plots and Egger test. The sensitivity analysis was carried out by the method of omitting any literature at a time. Combined with the results of subgroup analysis, the source of heterogeneity was also discussed absolutely. RESULTS: A total of 10 studies published between 2005 and 2016 were included in our analysis at last. The sample size ranged from 264 to 107,611 in included studies. The random effect models of meta-analysis showed that the overall carrier rate of SMA was 2.0% (95% confidence interval [CI], 1.7%-2.3%) in a heterogeneous set of studies (I = 64%). There was a gradual rise trend observed in the SMA carrier rate during the study period. The funnel plots and Egger test (Coef = 0.02, t = -0.45, P = .667 > .05) showed no obvious potential risk of publication bias. CONCLUSION: The overall carrying rate of SMA was high as 2.0% and may be on a slow upward trend. So it was recommended that the countries should take active and effective measures to roll out routine prenatal screening and health genetic counseling for SMA as early as possible. What is more, further studies also need to be conducted to explore the etiology and epidemic factors of SMA to better control the risk of this common birth defect.


Asunto(s)
Heterocigoto , Atrofia Muscular Espinal/epidemiología , Atrofia Muscular Espinal/genética , China/epidemiología , Humanos , Prevalencia
11.
Medicine (Baltimore) ; 99(3): e18809, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32011487

RESUMEN

In this article, the correlation between the copy number of survival motor neuron 2 (SMN2) gene, neuronal apoptosis inhibitory protein (NAIP), and the phenotype of spinal muscular atrophy patients were analyzed.Forty patients with spinal muscular atrophy (SMA) were included in the study at the Department of Medical Genetics of the First People's Hospital and the Department of Neurology of the Second People's Hospital in Yunnan Province from January 2012 to September 2018. Multiplex ligation-dependent probe amplification assay was performed to determine the copy numbers of SMN2 and NAIP genes. Statistical analysis was performed to determine the correlation between copy numbers of the SMN2 and NAIP genes and the clinical phenotypes of SMA.Our results show that among the 40 SMA patients, there were 13 type I cases, 16 type II cases and 11 type III cases. A total of 37 patients possessed a homozygous deletion of SMN1 exons 7 and 8, while the other 3 SMA patients possessed a single copy of SMN1 exon 8. There was no correlation between SMA subtypes and the deletion types of SMN1 exon 7 and 8 (P = .611). The percentage of 2, 3, and 4 copies of SMN2 exon 7 was 25.0%, 62.5%, and 12.5%, respectively. The percentage of 0, 1, and 2 copies of NAIP exon 5 was 10%, 57.5%, and 32.5%, respectively. The distributions of SMN2 and NAIP copy numbers among various SMA types were significantly different (all P < .05). Five combined SMN1-SMN2-NAIP genotypes were detected, of which 0-3-1 genotype had the highest proportion than the others, accounting for 42.5%. The copy number of SMN2 and NAIP gene had synergistic effect on SMA phenotype. The combined SMN1-SMN2-NAIP genotypes with fewer copies were associated with earlier onset age, higher mortality, and smaller average age at death in SMA patients.Therefore, we conclude that the copy number variance of SMN2 and NAIP is correlated with the SMA phenotype. Analysis of the copy number structure of the SMN1-SMN2-NAIP gene is helpful for SMA typing, disease prognosis prediction, and genetic counseling.


Asunto(s)
Dosificación de Gen , Atrofia Muscular Espinal/genética , Proteína Inhibidora de la Apoptosis Neuronal/genética , Adolescente , Niño , Preescolar , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Lactante , Masculino , Proteína 1 para la Supervivencia de la Neurona Motora/genética , Proteína 2 para la Supervivencia de la Neurona Motora/genética , Adulto Joven
12.
Nucleic Acids Res ; 48(6): 2853-2865, 2020 04 06.
Artículo en Inglés | MEDLINE | ID: mdl-32103257

RESUMEN

Spinal muscular atrophy (SMA) is a motor neuron disease. Nusinersen, a splice-switching antisense oligonucleotide (ASO), was the first approved drug to treat SMA. Based on prior preclinical studies, both 2'-O-methoxyethyl (MOE) with a phosphorothioate backbone and morpholino with a phosphorodiamidate backbone-with the same or extended target sequence as nusinersen-displayed efficient rescue of SMA mouse models. Here, we compared the therapeutic efficacy of these two modification chemistries in rescue of a severe mouse model using ASO10-29-a 2-nt longer version of nusinersen-via subcutaneous injection. Although both chemistries efficiently corrected SMN2 splicing in various tissues, restored motor function and improved the integrity of neuromuscular junctions, MOE-modified ASO10-29 (MOE10-29) was more efficacious than morpholino-modified ASO10-29 (PMO10-29) at the same molar dose, as seen by longer survival, greater body-weight gain and better preservation of motor neurons. Time-course analysis revealed that MOE10-29 had more persistent effects than PMO10-29. On the other hand, PMO10-29 appears to more readily cross an immature blood-brain barrier following systemic administration, showing more robust initial effects on SMN2 exon 7 inclusion, but less persistence in the central nervous system. We conclude that both modifications can be effective as splice-switching ASOs in the context of SMA and potentially other diseases, and discuss the advantages and disadvantages of each.


Asunto(s)
Amidas/química , Morfolinos/uso terapéutico , Atrofia Muscular Espinal/tratamiento farmacológico , Oligonucleótidos Antisentido/uso terapéutico , Ácidos Fosfóricos/química , Animales , Modelos Animales de Enfermedad , Exones/genética , Humanos , Ratones Transgénicos , Morfolinos/farmacología , Actividad Motora/efectos de los fármacos , Neuronas Motoras/efectos de los fármacos , Neuronas Motoras/patología , Músculos/patología , Atrofia Muscular Espinal/patología , Atrofia Muscular Espinal/fisiopatología , Unión Neuromuscular/patología , Unión Neuromuscular/fisiopatología , Oligonucleótidos Antisentido/farmacología , Fenotipo , Empalme del ARN/efectos de los fármacos , Empalme del ARN/genética , Médula Espinal/patología , Proteína 2 para la Supervivencia de la Neurona Motora/genética , Resultado del Tratamiento
13.
RNA ; 26(5): 595-612, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32051223

RESUMEN

Axonal protein synthesis has been shown to play a role in developmental and regenerative growth, as well as in the maintenance of the axoplasm in a steady state. Recent studies have begun to identify the mRNAs localized in axons, which could be translated locally under different conditions. Despite that by now hundreds or thousands of mRNAs have been shown to be localized into the axonal compartment of cultured neurons in vitro, knowledge of which mRNAs are localized in mature myelinated axons is quite limited. With the purpose of characterizing the transcriptome of mature myelinated motor axons of peripheral nervous systems, we modified the axon microdissection method devised by Koenig, enabling the isolation of the axoplasm RNA to perform RNA-seq analysis. The transcriptome analysis indicates that the number of RNAs detected in mature axons is lower in comparison with in vitro data, depleted of glial markers, and enriched in neuronal markers. The mature myelinated axons are enriched for mRNAs related to cytoskeleton, translation, and oxidative phosphorylation. Moreover, it was possible to define core genes present in axons when comparing our data with transcriptomic data of axons grown in different conditions. This work provides evidence that axon microdissection is a valuable method to obtain genome-wide data from mature and myelinated axons of the peripheral nervous system, and could be especially useful for the study of axonal involvement in neurodegenerative pathologies of motor neurons such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophies (SMA).


Asunto(s)
Esclerosis Amiotrófica Lateral/genética , Neuronas Motoras/metabolismo , Atrofia Muscular Espinal/genética , ARN/genética , Esclerosis Amiotrófica Lateral/metabolismo , Animales , Axones/metabolismo , Axones/patología , Diferenciación Celular/genética , Perfilación de la Expresión Génica , Humanos , Microdisección , Atrofia Muscular Espinal/metabolismo , Atrofia Muscular Espinal/patología , Sistema Nervioso Periférico/metabolismo , Sistema Nervioso Periférico/patología , ARN Mensajero/genética , RNA-Seq , Transcriptoma/genética
14.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(2): 116-122, 2020 Feb 10.
Artículo en Chino | MEDLINE | ID: mdl-32034734

RESUMEN

OBJECTIVE: To carry out genetic testing and prenatal diagnosis for 90 families affected with spinal muscular atrophy (SMA), and discuss the necessity for carrier screening. METHODS: All families were subjected to multiplex ligation-dependent probe amplification (MLPA) analysis. Combined MLPA and allele-specific PCR (AS-PCR) was used for prenatal diagnosis of the pregnant women. RESULTS: Among the 90 couples, 84 (93%) had a negative family history, 85 (94%) had given birth to an affected child before. Eighty-five husbands and 88 wives carried heterozygous deletion of exon 7 of the SMN1 gene. Two wives had homozygous deletion of exon 7 of the SMN1 gene and were affected. Prenatal diagnosis showed that 19 fetuses were SMA patients, 48 fetuses were carriers, and 23 fetuses were normal. Of note, eighteen affected fetuses were conceived by couples without a family history, which accounted for 20% of all pregnancies and 95% of all affected fetuses. CONCLUSION: To screen SMA carriers using MLPA and carry out prenatal diagnosis using combined MLPA and AS-PCR can ensure accurate diagnosis, which has a significant value for the prevention of SMA affected births.


Asunto(s)
Atrofia Muscular Espinal , Femenino , Pruebas Genéticas , Homocigoto , Humanos , Atrofia Muscular Espinal/genética , Embarazo , Diagnóstico Prenatal , Eliminación de Secuencia , Proteína 1 para la Supervivencia de la Neurona Motora
15.
Muscle Nerve ; 61(4): 530-534, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32012296

RESUMEN

INTRODUCTION: We aimed to investigate the correlation between body composition (BC) and spinal muscular atrophy (SMA)-specific motor function assessments. METHODS: Patients with SMA types I or II, aged 1 to 10 years, were recruited in this cross-sectional study. The protocol included anthropometric measurements, and dual-energy X-ray absoprtiometry to assess fat mass (FM), lean mass (LM), fat-free mass (FFM), FM and FFM indexes (FMI, FFMI), and motor function assessments (Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders scale for SMAI, and Hammersmith Functional Motor Scale-Expanded for SMAII). RESULTS: Eighty-eight children were included. All had a higher FM percentage than reference values. Motor function was moderately correlated with body mass index (BMI), FFMI, and LMI in SMAI, and weakly correlated with FFMI, LMI, and LM:FM ratio in SMAII. DISCUSSION: BC shows promise as a potential biomarker for SMA, but further studies are needed.


Asunto(s)
Tejido Adiposo/fisiopatología , Composición Corporal/fisiología , Atrofia Muscular Espinal/diagnóstico , Absorciometría de Fotón , Tejido Adiposo/diagnóstico por imagen , Biomarcadores , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Lactante , Masculino , Atrofia Muscular Espinal/diagnóstico por imagen , Atrofia Muscular Espinal/fisiopatología
16.
J Clin Neurosci ; 72: 114-118, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31980274

RESUMEN

Fluoroscopic-guided lumbar puncture (LP) is a procedure commonly performed by radiologists, which in some circumstances may be difficult or impossible using a traditional posterior interspinous or interlaminar approach. Alternatives to LP include cervical and cisternal punctures, placement of an Ommaya reservoir, and lumbar laminectomy. More recently, however, there has been a move toward access of the thecal sac through a transforaminal approach in patients with challenging anatomy. This report outlines our approach and experience using transforaminal LP (TFLP) in patients with spinal muscular atrophy (SMA) with a 100% success rate. We discuss its utility in other patients with difficult access and compare TFLP with other techniques to access the intrathecal space.


Asunto(s)
Laminectomía/métodos , Complicaciones Posoperatorias/epidemiología , Punción Espinal/métodos , Femenino , Fluoroscopía/métodos , Humanos , Laminectomía/efectos adversos , Masculino , Persona de Mediana Edad , Atrofia Muscular Espinal/diagnóstico por imagen , Atrofia Muscular Espinal/patología , Atrofia Muscular Espinal/cirugía , Complicaciones Posoperatorias/etiología , Punción Espinal/efectos adversos
17.
Rev Med Suisse ; 16(678): 154-155, 2020 Jan 22.
Artículo en Francés | MEDLINE | ID: mdl-31967762
18.
Expert Opin Pharmacother ; 21(3): 307-315, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31973611

RESUMEN

Introduction: Spinal muscular atrophy (SMA) is one of the most common inherited neuromuscular disorders. It causes progressive muscle weakness and results in significant disability. Until recently, there were no drugs available for the treatment of SMA. Several phase 1-3 studies, including three double-blind randomized placebo-controlled studies have demonstrated the efficacy of disease-modifying approaches including gene replacement therapy, antisense oligonucleotides, and splicing modifiers.Areas covered: This article covers the publically available data on therapeutic strategies that address the underlying cause of SMA and clinical data available on approved treatments and drugs in the pipeline.Expert opinion: The newer therapeutic options in SMA have a good safety profile and deliver a therapeutic benefit in most patients. It is essential that the recommended standards of care are delivered along with the drugs for the best outcomes. No biomarkers to distinguish responders from non-responders are available; it is important that biomarkers be identified. Early treatment is essential for the maximum efficacy of the newly available treatments.


Asunto(s)
Terapia Genética/métodos , Atrofia Muscular Espinal/terapia , Oligonucleótidos Antisentido/uso terapéutico , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto
19.
Rev Med Suisse ; 16(679): 248-249, 2020 Jan 29.
Artículo en Francés | MEDLINE | ID: mdl-31995327
20.
Neurol Neurochir Pol ; 54(1): 8-13, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31922583

RESUMEN

Spinal muscular atrophy (SMA) is a progressive neurodegenerative disease with an autosomal recessive trait of inheritance and great variability of its clinical course - from the lethal congenital type (SMA0) to the adult-onset form (SMA4). The disease is associated with a deficiency of SMN protein, which is encoded by two genes SMN1 and SMN2. Clinical symptoms depend on mutations in the SMN1 gene. The number of copies of twin similar SMN2 gene, which produces small amounts of SMN protein, is the main phenotype modifier, which determines the clinical severity of the disease. Until recently, it was considered that spinal cord motoneurons undergo selective loss. Recent studies have shown the role of SMN protein in various cellular processes and the multisystemic character of SMA. The aim of the therapeutic strategies developed so far has been to increase the expression of SMN protein by modifying the splicing of SMN2 gene (intrathecally administered antisense oligonucleotide - nusinersen; orally available small molecules: RG7916 and LMI070 or SMN1 gene replacement therapy (AAV9-SMN). The first SMN2-directed antisense oligonucleotide (nusinersen) has demonstrated in clinical trials high efficiency, and it has now been registered. The best effects were obtained in patients who were introduced to the drug in the pre symptomatic period. Studies on other substances are ongoing. The great advances in SMA therapy and increased understanding of the pathogenesis of the disease raise hopes for changes to the natural history of the disease. Simultaneously, it increases awareness of the need to improve the standard of patient care and early diagnosis (newborn screening). Many questions (e.g. emerging phenotypes, combined therapies, systemic vs. intrathecal administration, long-term consequences, and complications of the therapy) will require further studies and observations.


Asunto(s)
Atrofia Muscular Espinal , Humanos , Recién Nacido , Mutación , Fenotipo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA