Currarino syndrome is an uncommon genetic disease, with autosomal dominant inheritance, that is characterized by sacrococcygeal bone defect, presacral mass and anorectal malformation. There are many cases only diagnosed in adulthood, but early diagnosis is important to avoid life-threatening complications and to reduce morbidity, but it requires a high suspicion index and a multidisciplinary approach. If it is an unknown disease in the family, prenatal diagnosis is rare but possible. We discuss a case report of Currarino syndrome with an early diagnosis through fetal magnetic resonance imaging, studied during pregnancy for prenatal diagnosis purposes which showed similar defects in fetus spine and in the asymptomatic mother. We emphasize the inclusion of this rare syndrome in the differential diagnosis of fetal neural tube defects and caudal regression syndrome. The recognition of at-risk subjects should lead to better planning of pregnancies and appropriate management of affected children at birth.
Digestive System Abnormalities , Syringomyelia , Child , Infant, Newborn , Female , Pregnancy , Humans , Adult , Anal Canal , Rectum/diagnostic imaging , Digestive System Abnormalities/diagnosis , Syringomyelia/diagnosis
Fingolimod is a multiple sclerosis treatment licensed in Europe since 2011. Its efficacy has been demonstrated in three large phase III trials, used in the regulatory submissions throughout the world. As usual, in these trials the inclusion and exclusion criteria were designed to obtain a homogeneous population, with interchangeable characteristics in the different treatment arms. Although this is the best strategy to achieve a robust answer to the investigation question, it does not guaranty the treatment efficacy in the clinical practice, since in the real world there are concomitant treatments, comorbidities, adherence, and persistence challenges. But, to make informed treatment decision for a real life patient, we need to have evidence of the treatment efficacy, what has been called treatment effectiveness. This work aims to review fingolimod effectiveness, using, as source of information, abstracts, posters, and manuscripts. This unorthodox strategy was developed because more than half of the published experience with fingolimod is still on abstracts and posters. Only a small part of the studies reviewed are already published in peer reviewed journals. Fingolimod seems to be, at least, as effective and safe as it was on clinical trials, and with its long-term experience no new safety signals were observed.
Multiple Sclerosis (MS) is a chronic autoimmune disease of the Central Nervous System causing inflammation and neurodegeneration. There are only 3 epidemiological studies in Portugal, 2 in the Centre and 1 in the North, and there is the need to further study MS epidemiology in this country. The objective of this work is to contribute to the MS epidemiological knowledge in Portugal, describing the patients' epidemiological, demographic, and clinical characteristics in the Braga district of Portugal. This is a cross-sectional study of 345 patients followed in two hospitals of Braga district. These hospitals cover a resident population of 866,012 inhabitants. The data was collected from the clinical records, and 31/12/2009 was established as the prevalence day. For all MS patients, demographic characteristics and clinical outcomes are reported. We have found an incidence of 2.74/100,000 and a prevalence of 39.82/100,000 inhabitants. Most patients have an EDSS of 3 or lower and a mean age of 42 years. The diagnosis was done at mean age of 35, with RRMS being the disease type in more than 80% of patients. In this cohort, we found a female : male ratio of 1.79. More than 50% of patients are treated with Interferon ß-1b IM or IFNß-1a SC 22 µg.
Ectopia cordis is a rare congenital malformation, with an estimated incidence of 5 to 8 per million live births. It is defined as a malformation in which the heart is located in an extra-thoracic position. Ectopia cordis may occur as an isolated malformation or associated with other anomalies such as omphalocele, congenital heart disease or integrating Cantrell syndrome. The size and location of the defect influence the prognosis. Description: we report a case of a 24-year-old nulliparous woman, with no relevant family or personal history, in which the prenatal fetal ultrasound, performed at 21 weeks of gestation, revealed adefect of the anterior chest wall with exteriorization of the heart. Discussion: fetal echocardiography revealed a severe congenital heart disease. The parents decided to continue the pregnancy, after being duly informed by a multidisciplinary team. Delivery occurred at 37 weeks of gestation but the female newborn died one hour afterwards. Pathological examination confirmed the sonographic findings...
A ectopia cordis é uma malformação congênita rara, com uma incidência estimada de 5 a 8 por milhão de nados vivos. Define-se como uma malformação em que o coração se localiza numa posição extratorácica. Pode surgir como malformação isolada ou associada a outras anomalias como onfalocelo, doença cardíaca congênita ou integrando o síndrome de Cantrell. A dimensão e o local do defeito influenciam o prognóstico. Descrição: descreve-se um caso de uma mulher de 24 anos, nulípara, sem antecedentes pessoais oufamiliares relevantes, em que a ultrassonografiaobstétrica, realizada às 21 semanas, revelou um defeito da parede torácica anterior com exteriorização do coração. Discussão: o ecocardiograma fetal revelou uma cardiopatia congênita grave. Os pais decidiram continuar com a gravidez, após de devidamente informados por uma equipe multidisciplinar. O partoocorreu às 37 semanas, tendo o recém-nascido falecido cerca de 1 hora após o mesmo. O estudo anatomopatológico confirmou os achados ultrassonográficos...
Humans , Female , Pregnancy , Heart Defects, Congenital , Prenatal Care , Ectopia Cordis/diagnosis , Ectopia Cordis , Ultrasonography, Prenatal
Introducción. El fingolimod, un modulador del receptor de la esfingosina-1-fosfato (S1P) dotado de un mecanismo de acción novedoso, fue el primer tratamiento oral aprobado para la esclerosis múltiple remitente recurrente. Su unión a los receptores S1P1 de los linfocitos promueve la retención selectiva de los linfocitos T vírgenes y de memoria central en los tejidos linfoides secundarios, lo que impide su salida hacia el sistema nervioso central (SNC). Asimismo, el fingolimod atraviesa con facilidad la barrera hematoencefálica, y diversos estudios le atribuyen un efecto neuroprotector directo en el SNC. Objetivo. Revisar la información disponible acerca de los efectos centrales del fingolimod. Desarrollo. El desequilibrio entre los procesos lesivos y reparadores constituye un reflejo de la desmielinización crónica, la degeneración axonal y la gliosis, y parece contribuir a la discapacidad que la esclerosis múltiple acarrea. La facilidad con la que el fingolimod atraviesa la barrera hematoencefálica le permite actuar directamente sobre los receptores S1P localizados en las células del SNC. Una vez en el interior del SNC, ocupa los receptores S1P de los oligodendrocitos y de sus células precursoras, de los astrocitos, los microgliocitos y las neuronas, fomentando la remielinización, la neuroprotección y los procesos endógenos de regeneración. La eficacia evidenciada en los ensayos clínicos concuerda con un mecanismo de acción que incluiría efectos directos sobre las células del SNC. Conclusiones. Los datos disponibles indican que la eficacia del fingolimod en el tratamiento de la esclerosis múltiple se debe a su ambivalencia como molécula inmunomoduladora y moduladora directa de los receptores S1P del SNC. Tanto es así que estudios recientes le atribuyen efectos neuroprotectores en varios modelos que suscitan expectativas en torno a su posible aplicación terapéutica en la enfermedad de Alzheimer, el paludismo cerebral y el neuroblastoma, así como en la neuroprotección frente a la radioterapia craneal (AU)
Introduction. Fingolimod, a sphingosine-1-phosphate receptor modulator, was the first oral therapy approved for relapsingremitting multiple sclerosis, and shows a novel mechanism of action. Upon binding to S1P1 receptors in lymphocytes, the selective retention of naïve and central memory T cells in secondary lymphoid tissues is promoted, preventing their egress to the central nervous system (CNS). In addition, fingolimod readily crosses the blood brain barrier, and several reports suggest a direct neuroprotective effect in the CNS. Aim. To review the available data on the central effects of fingolimod. Development. Imbalances between damage and repair processes are a reflection of chronic demyelination, axonal degeneration and gliosis, and seem to contribute to multiple sclerosis associated disability. Given fingolimod readily crosses the blood brain barrier, it can exert its action directly on S1P receptors present in CNS cells. Fingolimod occupies S1P receptors in oligodendrocytes, oligodendrocyte precursor cells, astrocytes, microglial cells and neurons, promoting remyelination, neuroprotection, and endogenous regeneration processes. Efficacy results from clinical trials are consistent with a mechanism of action that includes direct effects in CNS cells. Conclusions. Current evidence suggests that the efficacy of fingolimod in the treatment of Multiple Sclerosis is due to its dual action as an immunomodulatory molecule and as a direct modulator of S1PRs in the CNS. In fact, recent reports propose that fingolimod has neuroprotective effects in several models, and open new avenues of potential therapeutic applications, such as Alzheimers disease, cerebral malaria, neuroblastoma and neuroprotection in cranial irradiation (AU)
Humans , Sphingosine/pharmacokinetics , Multiple Sclerosis, Relapsing-Remitting/drug therapy , T-Lymphocytes , Astrocytes , Oligodendroglia , Demyelinating Diseases/physiopathology , Neurodegenerative Diseases/physiopathology , Microglia , Neuroprotective Agents/pharmacokinetics
INTRODUCTION: Fingolimod, a sphingosine-1-phosphate receptor modulator, was the first oral therapy approved for relapsing-remitting multiple sclerosis, and shows a novel mechanism of action. Upon binding to S1P1 receptors in lymphocytes, the selective retention of naive and central memory T cells in secondary lymphoid tissues is promoted, preventing their egress to the central nervous system (CNS). In addition, fingolimod readily crosses the blood brain barrier, and several reports suggest a direct neuroprotective effect in the CNS. AIM: To review the available data on the central effects of fingolimod. DEVELOPMENT: Imbalances between damage and repair processes are a reflection of chronic demyelination, axonal degeneration and gliosis, and seem to contribute to multiple sclerosis associated disability. Given fingolimod readily crosses the blood brain barrier, it can exert its action directly on S1P receptors present in CNS cells. Fingolimod occupies S1P receptors in oligodendrocytes, oligodendrocyte precursor cells, astrocytes, microglial cells and neurons, promoting remyelination, neuroprotection, and endogenous regeneration processes. Efficacy results from clinical trials are consistent with a mechanism of action that includes direct effects in CNS cells. CONCLUSIONS: Current evidence suggests that the efficacy of fingolimod in the treatment of Multiple Sclerosis is due to its dual action as an immunomodulatory molecule and as a direct modulator of S1PRs in the CNS. In fact, recent reports propose that fingolimod has neuroprotective effects in several models, and open new avenues of potential therapeutic applications, such as Alzheimer's disease, cerebral malaria, neuroblastoma and neuroprotection in cranial irradiation.
TITLE: Efectos del fingolimod en el sistema nervioso central.Introduccion. El fingolimod, un modulador del receptor de la esfingosina-1-fosfato (S1P) dotado de un mecanismo de accion novedoso, fue el primer tratamiento oral aprobado para la esclerosis multiple remitente recurrente. Su union a los receptores S1P1 de los linfocitos promueve la retencion selectiva de los linfocitos T virgenes y de memoria central en los tejidos linfoides secundarios, lo que impide su salida hacia el sistema nervioso central (SNC). Asimismo, el fingolimod atraviesa con facilidad la barrera hematoencefalica, y diversos estudios le atribuyen un efecto neuroprotector directo en el SNC. Objetivo. Revisar la informacion disponible acerca de los efectos centrales del fingolimod. Desarrollo. El desequilibrio entre los procesos lesivos y reparadores constituye un reflejo de la desmielinizacion cronica, la degeneracion axonal y la gliosis, y parece contribuir a la discapacidad que la esclerosis multiple acarrea. La facilidad con la que el fingolimod atraviesa la barrera hematoencefalica le permite actuar directamente sobre los receptores S1P localizados en las celulas del SNC. Una vez en el interior del SNC, ocupa los receptores S1P de los oligodendrocitos y de sus celulas precursoras, de los astrocitos, los microgliocitos y las neuronas, fomentando la remielinizacion, la neuroproteccion y los procesos endogenos de regeneracion. La eficacia evidenciada en los ensayos clinicos concuerda con un mecanismo de accion que incluiria efectos directos sobre las celulas del SNC. Conclusiones. Los datos disponibles indican que la eficacia del fingolimod en el tratamiento de la esclerosis multiple se debe a su ambivalencia como molecula inmunomoduladora y moduladora directa de los receptores S1P del SNC. Tanto es asi que estudios recientes le atribuyen efectos neuroprotectores en varios modelos que suscitan expectativas en torno a su posible aplicacion terapeutica en la enfermedad de Alzheimer, el paludismo cerebral y el neuroblastoma, asi como en la neuroproteccion frente a la radioterapia craneal.
Neuroprotective Agents/pharmacology , Propylene Glycols/pharmacology , Sphingosine/analogs & derivatives , Animals , Blood-Brain Barrier , Chemotaxis, Leukocyte/drug effects , Clinical Trials as Topic , Disease Models, Animal , Fingolimod Hydrochloride , Humans , Immunologic Memory , Mice , Mice, Knockout , Mice, Neurologic Mutants , Multicenter Studies as Topic , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Neurogenesis/drug effects , Neuroglia/drug effects , Neuroprotective Agents/pharmacokinetics , Propylene Glycols/pharmacokinetics , Propylene Glycols/therapeutic use , Rats , Receptors, Lysosphingolipid/drug effects , Sphingosine/pharmacokinetics , Sphingosine/pharmacology , Sphingosine/therapeutic use , T-Lymphocyte Subsets/drug effects , T-Lymphocyte Subsets/immunology
