scholarly journals Dravet Syndrome: Addressing the Needs of Patients and Families: Introduction

2016 ◽  
Vol 43 (S3) ◽  
pp. S1-S2
Author(s):  
Charlotte Dravet
Keyword(s):  
Therapeutic Strategy ◽  
Seizure Control ◽  
Epileptic Seizures ◽  
Dravet Syndrome ◽  
First Year ◽  
Family Needs ◽  
Live Births ◽  
Number Of Patients ◽  
Underlying Mechanisms ◽  
First Year Of Life

AbstractDravet syndrome is not one of the most frequent severe epilepsies affecting infants during the first year of life. In the most recent epidemiological study, in Sweden, its estimated incidence was 1 in 33,000 live births. On December 31, 2011, its prevalence was 1 in 45,700 children aged less than 18 years. Nonetheless, it is now well known by many child neurologists for several reasons. First, its genetic aetiology was demonstrated almost 15 years ago, and an animal model was created shortly thereafter, allowing experimental work focused on the underlying mechanisms of the disease. Second, the clinical characteristics of the typical form of Dravet syndrome are well defined, enough to allow early diagnosis. Third, although the epileptic seizures are highly pharmacoresistant, we now have at our disposal a specific therapeutic strategy that allows one to avoid the most severe seizures in a number of patients due to the new drug stiripentol, used in different associations. Nevertheless, this therapeutic strategy should not be limited to seizure control and needs to take into account all other aspects of the disease. The aim of this symposium is to present a synthesis of the diagnosis and treatment of Dravet syndrome with a focus on family needs.

scholarly journals Dravet syndrome associated mutations in GABRA1, GABRB2 and GABRG2 define the genetic landscape of defects of GABAA receptors

2021 ◽  
Author(s):  
Ciria C Hernandez ◽  
XiaoJuan Tian ◽  
Ningning Hu ◽  
Wangzhen Shen ◽  
Mackenzie A Catron ◽  
...  
Keyword(s):  
Gabaa Receptor ◽  
De Novo ◽  
Epileptic Encephalopathy ◽  
Dravet Syndrome ◽  
First Year ◽  
Genes Encoding ◽  
Genetic Landscape ◽  
Clonic Seizures ◽  
Trafficking Defects ◽  
First Year Of Life

Abstract Dravet syndrome is a rare, catastrophic epileptic encephalopathy that begins in the first year of life, usually with febrile or afebrile hemiclonic or generalized tonic-clonic seizures followed by status epilepticus. De novo variants in genes that mediate synaptic transmission such as SCN1A and PCDH19 are often associated with Dravet syndrome. Recently, GABAA receptor subunit genes (GABRs) encoding α1 (GABRA1), β3 (GABRB3) and γ2 (GABRG2), but not β2 (GABRB2) or β1 (GABRB1), subunits are frequently associated with Dravet syndrome or Dravet syndrome-like phenotype. We performed next generation sequencing on 870 patients with Dravet syndrome and identified nine variants in three different GABRs. Interestingly, the variants were all in genes encoding the most common GABAA receptor, the α1β2γ2 receptor. Mutations in GABRA1 (c.644T>C, p.L215P; c.640C>T, p.R214C; c.859G>A; V287I; c.641G>A, p.R214H) and GABRG2 (c.269C>G, p.T90R; c.1025C>T, p.P342L) presented as de novo cases, while in GABRB2 two variants were de novo (c.992T>C, p.F331S; c.542A>T, p.Y181F) and one was autosomal dominant and inherited from the maternal side (c.990_992del, p.330_331del). We characterized the effects of these GABR variants on GABAA receptor biogenesis and channel function. We found that defects in receptor gating were the common deficiency of GABRA1 and GABRB2 Dravet syndrome variants, while mainly trafficking defects were found with the GABRG2 (c.269C>G, p.T90R) variant. It seems that variants in α1 and β2 subunits are less tolerated than in γ2 subunits, since variant α1 and β2 subunits express well but were functionally deficient. This suggests that all of these GABR variants are all targeting GABR genes that encode the assembled α1β2γ2 receptor, and regardless of which of the three subunits are mutated, variants in genes coding for α1, β2 and γ2 receptor subunits make them candidate causative genes in the pathogenesis of Dravet syndrome.

scholarly journals Efficacy and safety of fenfluramine in the treatment of Dravet syndrome - literature review

2022 ◽  
Vol 12 (1) ◽  
pp. 106-116
Author(s):  
Martyna Stefaniak ◽  
Zofia Pietrzak ◽  
Piotr Dzikowski ◽  
Emilia Nowicka ◽  
Michał Obel ◽  
...  
Keyword(s):  
Oral Solution ◽  
Dravet Syndrome ◽  
First Year ◽  
Efficacy And Safety ◽  
Anti Epileptic Drug ◽  
Drug Regimens ◽  
Pulmonary Arterial ◽  
First Year Of Life ◽  
Patients Experience ◽  
Oral Doses

Dravet Syndrome is a severe, drug-resistant, and rare epileptiform disorder that is typically presented in the first year of life in an otherwise healthy child. It is characterized by prolonged seizures that are often resistant to current anti-epileptic drug regimens, which made them poorly controlled, and almost 50% of patients experience at least four tonic-clonic seizures per month. There are three new medicines: stiripentol, cannabidiol, and fenfluramine, with documented efficacy and safety as adjunctive therapies in pharmacoresistant Dravet syndrome treatment. This study aimed to assess the efficacy and safety of fenfluramine in the treatment of Dravet syndrome. Our study material consisted of publications, which were found in PubMed, Google Scholar, and Embase databases. In order to find the proper publications, the search has been conducted with the use of a combination of keywords like: “fenfluramine”, “Dravet syndrome”, “epilepsy treatment”, “Dravet syndrome pediatric patients”. The first step was to find proper publications from the last 10 years. The second step was to carry out an overview of the found publications. Results of mentioned studies proved that in Dravet syndrome, fenfluramine provided a significantly greater reduction in convulsive seizure frequency compared with placebo. No patient developed valvular heart disease or pulmonary arterial hypertension, the side effects that occurred during its use were mild and the drug was generally well-tolerated. The bioequivalence and tolerability of single oral doses of fenfluramine hydrochloride oral solution in the fed and fasted states support drug administration without regard to meals. Fenfluramine may represent a new important treatment option for Dravet syndrome.

Complex Congenital Heart Defect, Heterotaxy, Imperforate Anus, and Other Congenital Anomalies in a 27-Week Infant: A Case Study

2014 ◽  
Vol 33 (4) ◽  
pp. 199-203 ◽  
Author(s):  
Angela Koerner
Keyword(s):  
Congenital Anomalies ◽  
Intraventricular Hemorrhage ◽  
Congenital Heart ◽  
Surgical Intervention ◽  
First Year ◽  
Risk Of Infection ◽  
Cardiac Defects ◽  
Live Births ◽  
First Year Of Life

According to multiple researchers and studies, congenital heart disease (CHD) occurs in approximately 4.8–12.0 of 1,000 live births in the general population, and 2.4 per 1,000 cases are serious enough to require surgery or cardiac catheterization in the first year of life.1 Historically, it has been assumed that the earlier the gestational age with CHD, the poorer the outcome; however, with continued improvements in neonatal care, this hypothesis should be looked at more closely. This case illustrates the challenges associated with prematurity, complex cardiac defects, intraventricular hemorrhage (IVH), and other congenital anomalies that increase the risk of infection and/or surgical intervention. It will discuss the hospital course of a twin, born at 27 weeks gestation, who was found to have all of these diagnoses, yet, despite the complexity of his case, he had a predominantly uncomplicated hospital course.

scholarly journals Analysis of the health status of children of the first year of life

2020 ◽  
pp. 24-32
Author(s):  
R.V. Marushko ◽  
◽  
О.О. Dudina ◽  
T.L. Marushko ◽  
◽  
...  
Keyword(s):  
Growth Rate ◽  
Birth Weight ◽  
Infant Mortality ◽  
Low Birth Weight ◽  
Negative Trend ◽  
Child Health Service ◽  
First Year ◽  
Live Births ◽  
The Past ◽  
First Year Of Life

Ukraine entered the 21st century with one of the worst vital signs in Europe and the burden of many socio-economic and demographic problems. Adverse quantitative and especially qualitative indicators of population reproduction have become stable. Therefore, the most important medical and social task and one of the main activities of the Ministry of Health of Ukraine is the formation and maintenance of public health. The defining stage in the formation of human health is the first year of life. Purpose — to study the state and trends of changes in the main indicators of the health of children in the first year of life for the period 2000–2019. Materials and methods. A retrospective analysis of the incidence of children in the first year of life, infant mortality, over the past 20 years in the context of individual pathological conditions is carried out. The information base of the study was the data of state and industry statistics for 2000–2019. Methods of a systematic approach, statistical data processing, epidemiological analysis of graphic images were used. Results. The study revealed that the unfavorable demographic situation in Ukraine is accompanied by an unsatisfactory state of the main predictors of a healthy start in the life of infants, the formation and maintenance of their health. Over the past two decades, there has been a high level with a negative trend of diseases of the reproductive system of women, a high frequency of the combination of pregnancy and extragenital diseases remains. There is a negative trend towards an increase in the generalized objective criterion of the health of the generation, which is born and the socio-economic well-being of the population — the frequency of premature, low birth weight, incl. With very low birth weight. Only thanks to the introduction of modern medical organizational technologies with proven efficiency in the activities of the maternal and child health service was it possible to achieve a decrease in the incidence of newborns from 280.8 per 1000 live births in 2000 up to 172.14 in 2019. At the same time, the increase in the incidence of newborns with diseases that have a direct impact on the development of chronic and disabling diseases at all stages of life is of concern — congenital pneumonia, neonatal sepsis, other disorders of the cerebral status of the newborn, neonatal jaundice. According to the assessment of the dynamics of the general morbidity of children in the first year of life, its level is still high, with a positive trend — 2018.8 per 1000 children who reached 1 year in 2000 and 1393.1 in 2019, the growth rate is -30.9% with a traditionally leading position in the level and structure of the incidence of respiratory diseases — 810.2 per 1000 children who have reached one year of life and 58.15%, certain conditions occurring in perinatal period — 126.7 ‰ and 9.06%, diseases of the skin and subcutaneous tissue — 63.9‰ and 4.59%, diseases of the blood and hematopoietic organs and certain disorders involving the immune mechanism — 63.0‰ and 4.52%. Conclusions. The positive dynamics of morbidity in children of the first year of life is confirmed by a decrease in infant mortality from its maximum level of 11.9 per 1000 live births in 2000 up to 7.0 in 2019, the growth rate is -41.2% due to all its components with a more intensive reduction in postneonatal mortality from 5.28‰ to 2.57‰, the growth rate is -51.3% against the background of an increase in the concentration of mortality in the neonatal period from 55.9% to 64.5%, respectively. No conflict of interest was declared by the authors. Key words: newborns, children of the first year of life, low birthweight newborns, morbidity, infant mortality.

Bilateral ocular involvement in congenital toxoplasmosis: A case report and literature review

2021 ◽  
pp. 004947552098638
Author(s):  
Melis Deniz ◽  
Anıl Tapısız ◽  
Hasan Tezer ◽  
Tugba Bedir Demirdag
Keyword(s):  
Case Report ◽  
Literature Review ◽  
Primary Infection ◽  
Visual Loss ◽  
Parasitic Infection ◽  
Congenital Toxoplasmosis ◽  
First Year ◽  
Ocular Involvement ◽  
Live Births ◽  
First Year Of Life

We report a case of neuro-ophthalmological complications of congenital toxoplasmosis, a parasitic infection caused by Toxoplasma gondi. Its congenital form occurs either as a primary infection or as reactivation of the same due to immunosuppression during pregnancy. With an incidence rate of 1.5/1000 live births, this disease is an important cause of visual loss from chorio-retinal lesions in >82%. Recent studies have shown that treatment given in utero and in the first year of life can reduce ophthalmological complications.

scholarly journals Epilepsy combined with Wolf-Hirschhorn syndrome: a literature review and description of clinical cases

2019 ◽  
Vol 10 (4) ◽  
pp. 39-52
Author(s):  
M. B. Mironov ◽  
N. V. Chebanenko ◽  
S. O. Ayvazyan ◽  
S. A. Vladimirova ◽  
K. V. Osipova ◽  
...  
Keyword(s):  
Epileptiform Activity ◽  
Epileptic Seizures ◽  
Febrile Seizures ◽  
First Year ◽  
Eeg Activity ◽  
Epileptic Spasms ◽  
High Incidence ◽  
Clonic Seizures ◽  
First Year Of Life ◽  
Patients With Epilepsy

This article presents the anamnestic, clinical, electro-encephalographic and neuroimaging findings in 5 patients with epilepsy combined with Wolf-Hirschhorn syndrome (WHS). According to our data and the results of others, this combination has its specific characteristics. These include: a high incidence of epilepsy in patients with WHS (50-100% of cases), an early debut of seizures (mainly in the first year of life), fever-provoked seizures, and a variety of seizure types – focal paroxysms, bilateral tonic-clonic seizures, atypical febrile seizures, atypical absences and epileptic spasms. In addition, there may be frequent epileptic seizures tending toward status epilepticus, a slowing of the major EEG activity, a local EEG slowing (mainly in the posterior and bi-frontal areas), and regional / multiregional epileptiform activity. In more than 50% of cases, the diffuse peakwave activity is observed; the broad spectrum anti-epileptic drugs are highly efficient in 80% of cases. Based on this study, we propose recommendations for the management of patients with epilepsy combined with WHS.

Statement on Infant Mortality

PEDIATRICS ◽  
1986 ◽  
Vol 78 (6) ◽  
pp. 1155-1160
Author(s):  
Keyword(s):  
Mortality Rate ◽  
Child Health ◽  
Infant Mortality ◽  
Neonatal Mortality ◽  
Mortality Rates ◽  
First Year ◽  
Postneonatal Mortality ◽  
Factors Affecting ◽  
Live Births ◽  
First Year Of Life

Why Is Infant Mortality Important? Rates of infant mortality are sensitive indicators of a broad range of factors affecting children's health. As such, infant mortality is the "tip of the iceberg" of child health problems, and changes in infant mortality are a signal of factors affecting child health more broadly. In addition to its role as a general gauge of child health, infant mortality itself represents an important health problem. It is well to remember that infant death rates are the highest of any age group less than 65 years. The message conveyed by infant mortality rates if better understood in terms of the causes of mortality at different times during the first year of life. Neonatal Mortality Neonatal mortality rate is defined as the number of infants dying between 0 and 27 days of life per 1,000 live births. These deaths in the first month of life reflect primarily factors associated with health of the mother before and during pregnancy and the special problems of the newborn. Deaths in this age range result chiefly from inadequate intruterine growth (prematurity, intrauterine growth retardation) and congenital anomalies. As a result, neonatal mortality rates provide an indicator of the factors affecting pregnancy, delivery, and the neonate and the adequacy of services in the prenatal, intrapartum, and neonatal periods. Postneonatal Mortality Postneonatal mortality rate is defined as the number of infants dying between 28 days and 11 months of life per 1,000 live births, ie, deaths occurring during the remainder of the first year of life.

ECHO 9 VIRUS INFECTION AND CONGENITAL ABNORMALITIES: A NEGATIVE REPORT

PEDIATRICS ◽  
1962 ◽  
Vol 29 (2) ◽  
pp. 261-269
Author(s):  
Herman Kleinman ◽  
James T. Prince ◽  
Wayne E. Mathey ◽  
Abraham B. Rosenfleld ◽  
Jacob E. Bearman ◽  
...  
Keyword(s):  
Public Health ◽  
Cord Blood ◽  
Congenital Anomalies ◽  
First Trimester ◽  
Public Health Nurses ◽  
Congenital Defects ◽  
First Year ◽  
Live Births ◽  
Echo Virus ◽  
First Year Of Life

Approximately 200,000 residents of Hennepin and Ramsey counties in Minnesota developed an aseptic meningitis syndrome during the summer and fall of 1957. One fourth of the patients had a maculopapular rash very similar to that of rubella. The etiologic agent was found to be ECHO virus type 9. This epidemic provided an opportunity to determine whether infection with this virus during the first trimester of pregnancy could be related to the appearance of congenital defects such as occurs in rubella. From March 3 through June 13, 1958, 10,109 liveborn infants and 105 stillborn infants were delivered in the 12 Minneapolis and 10 St. Paul hospitals serving these two counties. All mothers had been exposed to the 1957 epidemic. Public health nurses interviewed 9,990 mothers in the hospitals within a few days after birth for detailed histories of infection during pregnancy. On the basis of these interviews it was judged that 6.5% of the mothers had historic evidence of an ECHO 9 infection during pregnancy. Serologic evidence of ECHO 9 infection in the recent past was present in 19% of 853 antibody titrations carried out on cord blood specimens from abnormals and normals (controls). To discover anomalies not recognized at birth, a follow-up was carried out 11 to 12 months later by the public health nurses by telephone interviews of some 9,600 mothers. There were 356 major and minor congenital anomalies recognized during the first year of life. An additional 63 hernias were diagnosed during the first year for a total of 419 anomalies found in 10,109 live births in the study. This rate of 41.4 total anomalies per 1,000 live births, or 4.1%, is well within the rates reported by other authors. A total of 39.6% of the anomalies were diagnosed at birth and 60.4% during the first year of life. Of the anomalies, 61% occurred in males and 39% in females; 1.5% of the infants had major abnormalities and 0.74% died as a result of these anomalies during their first year of life. There were 105 stillbirths recorded, or 10.4 per 1,000 live births. This compares with a rate of 13.6 for Hennepin and Ramsey counties for the year. Among the stillbirths, 11.4% died from congenital anomalies, in comparison with 10.95% statewide for the year. A statistical analysis of the findings which compares the ECHO 9 antibody titer distributions in the cord blood of the normal and the abnormal infants does not justify the conclusion that ECHO 9 infection in the mother increases the incidence of congenital anomalies in the offspring. The only exception to this generalization is in the case of skin abnormalities, where there is a statistical suggestion of association.

COMPARATIVE FREQUENCY OF DETECTION OF ENTEROPATHOGENIC E. COLI, SALMONELLA AND SHIGELLA IN RECTAL SWAB CULTURES FROM INFANTS AND YOUNG CHILDREN

PEDIATRICS ◽  
1957 ◽  
Vol 19 (3) ◽  
pp. 411-423
Author(s):  
Merlin L. Cooper ◽  
Helen M. Keller ◽  
Edward W. Walters
Keyword(s):  
Young Children ◽  
Rectal Swab ◽  
Multiple Infections ◽  
First Year ◽  
Isolation And Identification ◽  
E Coli ◽  
Salmonella Infections ◽  
Number Of Patients ◽  
First Year Of Life ◽  
Infants And Young Children

The present report supplies the details and results of a study of 2,865 patients during a period of 2 years, March 1, 1954, to March 1, 1956. The purpose of the study was to determine the comparative frequency of isolation of Salmonella, Shigella and nine serotypes of enteropathogenic E. coli from rectal swab cultures obtained from infants and young children admitted to the Children's Hospital. The technic for the isolation and identification of enteropathogenic E. coli is described. A diagnostic polyvalent E. coli antiserum prepared in our laboratory was very helpful in the preliminary detection of nine serotypes of enteropathogenic E. coli. Salmonellae were isolated from 85 patients, Shigellae from 88 and one of the nine serotypes of enteropathogenic E. coli from each of 188 patients. Seventeen serotypes of Salmonella were isolated from 85 patients. Salmonella sp. (Type oranienburg) and Sal. typhimurium were isolated most frequently. Shigellae were isolated from a total of 88 patients; Sh. sonnei from 53 and five serotypes of Sh. flexneri from 35 patients. One of the nine serotypes of enteropathogenic E. coli was isolated from each of 188 patients. E. coli 055:B5 was detected in cultures from 63 patients and was detected most frequently. E. coli 0111:B4, 0126:B16 and 026:B6 were found next most frequently. Of the 361 patients from whom Salmonella, Shigella or enteropathogenic E. coli were isolated, rectal swab cultures were obtained at the time of admission from 317. Of these, 287 (91%) were positive. The incidence of diarrhea in the three groups was comparable: 95% of the patients from whom Salmonellae were isolated, 98% of patients from whom Shigellae were isolated and 92% of patients harboring enteropathogenic E. coli. Infections due to Salmonella or enteropathogenic E. coli were more frequent in the first year of life and infections due to Shigella occurred more frequently in the second year of life. The majority of patients with diarrhea and with rectal swab cultures negative for Salmonella, Shigella and enteropathogenic E. coli were in the first year of life. The incidence of Salmonella infections did not show any seasonal predominance; the Shigella infections were most frequent in September and October and the enteropathogenic E. coli infections in November and October. The highest incidence of diarrheal infections among patients whose rectal swab cultures were negative for these three groups of bacteria occurred in December and January of each of the 2 years of this study. The incidence of enteropathogenic E. coli infections exceeded those due to Shigella or Salmonella during 15 of the 24 months of this study. Sporadic infections due to these three groups of bacteria occurred throughout the 2-year period. Successive and/or multiple infections with Salmonella, Shigella or enteropathogenic E. coli occurred in 15 paients. Infection with one serotype of enteropathogenic E. coli did not protect seven patients from subsequent infection with another serotype. The convalescent carrier rate was 36.6% for the patients with Salmonella infections, 2.6% for those with Shigella infections and 8.3% for those from whom enteropathogenic E. coli had been isolated. The mortality rate was 1.2% among patients with Salmonella infections and 1.6% among the patients from whom enteropathogenic E. coli had been isolated. None of the patients with Shigella infections died. The large number of patients, 889, with diarrhea and with rectal swab cultures negative for Salmonella, Shigella and enteropathogenic E. coli indicates a need for continued investigation into the etiology of diarrhea in infants and young children.

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