Adult Syndrome Research Articles

Lennox–Gastaut syndrome in adulthood: Long-term clinical follow-up of 38 patients and analysis of their recorded seizures

Lennox–Gastaut syndrome (LGS) is a severe epileptic encephalopathy with childhood onset that usually continues through adolescence and into adulthood. In the long term, patients with this condition still have intractable seizures, intellectual disability, behavioral problems, and physical comorbidities. The aim of this study was to describe the clinical and EEG characteristics of a group of adults with Lennox–Gastaut syndrome. We identified 38 (22 females, 16 males) patients with LGS older than age 18years at their last evaluation, with mean age of 43.3±10.6years. Median follow-up was 14.4years (range: 2–40).All of our patients had 3 or more seizure types during their clinical history. The most prevalent seizure types at follow-up were atypical absences (28/38), tonic (28/38), generalized tonic–clonic (17/38), focal (11/38), and myoclonic seizures (9/38). All patients had drug-resistant seizures. Besides epilepsy, intellectual disability and behavioral problems were prominent features. Surprisingly, paroxysmal nonepileptic seizures were reported in 3 patients. Our observations confirm the poor outcome of Lennox–Gastaut syndrome through adulthood, regardless of age at seizure onset, etiology, and history of previous West syndrome.

Overweight or obesity in children aged 0 to 6 and the risk of adult metabolic syndrome: A systematic review and meta-analysis.

To identify an association between overweight or obesity in early childhood and metabolic syndrome in adults. Early childhood overweight or obesity is important because it can predict metabolic syndrome in adulthood. A longer period of overweight or obesity leads to the accumulation of more risk factors. However, there are insufficient and inconsistent studies on this issue. A systematic review and meta-analysis. We followed the Meta-Analysis of Observational Studies in Epidemiology guideline, MEDLINE, EMBASE, Cochrane library and CINAHL electronic databases as well as reference lists of included studies were searched, without published date restriction. We used the Newcastle-Ottawa Scale to assess the quality of the observational studies in the systematic review, and the meta-analysis was performed using random-effects models. All of the included studies were published from 2008-2014, and the participants of this study were only Asians or Europeans. A total of 12 results from five studies were included in the meta-analysis. Overweight or obesity in early childhood was associated with a higher risk of adult metabolic syndrome compared with the controls. When confirmed in each age group (at birth, 0-2 and 2-6years), there was a statistically significant difference before and after the age of 2years. As a result of the meta-regression, when the age of the children increased, the effect size of adult metabolic syndrome for overweight or obesity also increased. The results confirm that the aetiology of metabolic syndrome includes long-term impacts from the early stage of life and indicate that early intervention for overweight or obesity is needed. these findings could help community and clinical health nurses recognize the risk of overweight or obesity in early life, and provide evidence to develop and implement the preventive intervention for early childhood.

Loss of Vagal Sensitivity to Cholecystokinin in Rats Born with Intrauterine Growth Retardation and Consequence on Food Intake.

Perinatal malnutrition is associated with low birth weight and an increased risk of developing metabolic syndrome in adulthood. Modification of food intake (FI) regulation was observed in adult rats born with intrauterine growth retardation induced by maternal dietary protein restriction during gestation and maintained restricted until weaning. Gastrointestinal peptides and particularly cholecystokinin (CCK) play a major role in short-term regulation of FI by relaying digestive signals to the hindbrain via the vagal afferent nerve (VAN). We hypothesized that vagal sensitivity to CCK could be affected in rats suffering from undernutrition [low protein (LP)] during fetal and postnatal life, leading to an altered gut–brain communication and impacting satiation. Our aim was to study short-term FI along with signals of appetite and satiation in adult LP rats compared to control rats. The dose–response to CCK injection was investigated on FI as well as the associated signaling pathways activated in nodose ganglia. We showed that LP rats have a reduced first-meal satiety ratio after a fasting period associated to a higher postprandial plasmatic CCK release, a reduced sensitivity to CCK when injected at low concentration and a reduced presence of CCK-1 receptor in nodose ganglia. Accordingly, the lower basal and CCK-induced phosphorylation of calcium/calmodulin-dependent protein kinase in nodose ganglia of LP rats could reflect an under-expressed vanilloid family of transient receptor potential cation channels on VAN. Altogether, the present data demonstrated a reduced vagal sensitivity to CCK in LP rats at adulthood, which could contribute to deregulation of FI reported in this model.

Maternal Separation Induced Visceral Hypersensitivity from Childhood to Adulthood.

Background/AimsEarly adverse life events (EALs) are relevant to irritable bowel syndrome in adulthood. Maternal separation (MS), as one of the EALs, has proved to induce visceral hypersensitivity in adult rats. However, the effect of MS on visceral hypersensitvity from the post-weaning period to adulthood remains unknown.MethodsOne hundred and ten neonatal Sprague-Dawley rats were randomly divided into 2 groups: rats in the MS group were exposed to 3 hours daily MS on postnatal day (PND) 2–14; the normal control (NC) group remained undisturbed. Visceral sensitivity was determined by measuring the visceromotor response to colorectal distention on PND21, 35, and 56. Anxiety-like behaviors were measured by the open field test.ResultsCompared with NC rats, MS rats showed significant visceral hypersensitivity from the post-weaning period to adult. The proportion of visceral hypersensitive rats decreased with age from 87.5% to 70.0% in the female MS group and from 90.0% to 66.7% in the male MS group. The relative VMR ratio of MS and NC on PND21 was higher than PND35 and PND56. MS rats showed decreased ability of movement and exploration to the novel environment in the post-weaning period, obesity in the prepubertal period, and more anxiety-like behaviors in adulthood.ConclusionsMS can significantly affect visceral sensitivity and behaviors of rats in different age stages, especially in the post-weaning period. Visceral hypersensitivity of MS rats is more pronounced in the post-weaning period and slightly restored in adults. Thus, visceral hypersensitivity in the post-weaning period might play a more meaningful pathophysiologic role in the formation of adult irritable bowel syndrome.

Stress reactivity and its effects on subsequent food intake in depressed and healthy women with and without adverse childhood experiences

BackgroundAdverse childhood experiences (ACE) increase the risk to develop major depressive disorder (MDD) and obesity or metabolic syndrome in adulthood. In addition, ACE may be associated with an exaggerated endocrine response to stress, which, in turn, may lead to enhanced food intake resulting in obesity and metabolic problems. MethodsWe systematically examined the stress response and consecutive food intake in 32 women with MDD and ACE as determined by a clinical interview (Early Trauma Inventory), 52 women with MDD without ACE, 22 women with ACE but no current or lifetime MDD and 37 healthy women without either MDD or ACE. All participants underwent a psychosocial stress test (Trier Social Stress Test, TSST) and a control condition (Placebo-TSST) before they were offered a buffet of snacks. Participants were not aware that the primary outcome variable was the amount of consumed kilocalories (kcal). ResultsThe four groups did not differ in demographic variables. Stress resulted in higher cortisol release and higher blood pressure compared to the control condition. Patients with MDD without ACE had a significantly lower cortisol response to stress compared to controls. Across groups, we found higher kcal intake after stress compared to the control condition. Comparing high and low cortisol responders to stress, higher kcal intake after stress was only seen in those with low cortisol release. ConclusionsThis study provides evidence that blunted rather than enhanced cortisol release to stress might lead to increased food intake, independent from MDD and ACE.

Neonatal bladder inflammation induces long-term visceral pain and altered responses of spinal neurons in adult rats

Painful events early in life have been shown to increase the incidence of interstitial cystitis/painful bladder syndrome in adulthood. However, the intrinsic mechanism is not well studied. We previously reported that neonatal bladder inflammation causes chronic visceral hypersensitivity along with molecular disruption of spinal GABAergic system in rats. The present study investigates whether these molecular changes affect the integrative function and responses of bladder-sensitive primary afferent and spinal neurons. Neonatal bladder inflammation was induced by intravesicular injection of zymosan during postnatal (P) days 14–16. In adulthood (P60), the viscero-motor response (VMR) to visceral stimuli was significantly inhibited by intrathecal (i.t) HZ166 (GABAAα-2 agonist) only in neonatally saline-treated, but not in neonatally zymosan-treated rats. HZ166 significantly inhibited the responses of bladder-responsive lumbosacral (LS) spinal neurons to urinary bladder distension (UBD) and slow infusion (SI) in neonatally saline-treated rats. Similar results were also observed in naïve adult rats where HZ166 produced significant inhibition of bladder-responsive spinal neurons. However, HZ166 did not inhibit responses of UBD-responsive spinal neurons from neonatally zymosan-treated rats. The drug did not attenuate the responses of UBD-sensitive pelvic nerve afferent (PNA) fibers to UBD and SI in either group of rats tested. Immunohistochemical studies showed a significantly lower level of GABAAα-2 receptor expression in the LS spinal cord of neonatally zymosan-treated rats compared to saline-treated rats. These findings indicate that neonatal bladder inflammation leads to functional and molecular alteration of spinal GABAAα-2 receptor subtypes, which may result in chronic visceral hyperalgesia in adulthood.

ARCAPA Syndrome in Adulthood

ARCAPA Syndrome in Adulthood

Hyper-IgE syndrome in adulthood: a case report and literature review

Objective: To describe the clinical features of hyper-IgE syndrome (HIES), with emphasis on refractory pulmonary cystic lesions as the initial presentation in adulthood. Methods: A case of HIES presenting with pulmonary cystic lesions in an adult patient was retrospectively analyzed. We used "hyper-IgE syndrome" as the Chinese keywords, "hyper-IgE syndrome, China" as the English keywords to retrieve the literature from Wanfang database/CNKI database and Pubmed database until April 2016. The clinical data were pooled and analyzed. Results: A 19 year old female patient was admitted to our hospital because of recurrent cough and expectoration as the chief complaint. Physical examination revealed broad nasal bridge and scoliosis, and chest CT showed gradually enlarged and increased cystic lesions. Laboratory studies demonstrated significantly increased blood eosinophils and serum level of total IgE, together with a definite chemotactic dysfunction of neutrophils. A further detection of STAT3 mutation was negative. The diagnosis of HIES was made and antibiotic treatment resulted in disease remission. Literature review found 45 reports including 37 in Chinese and 11 in English. Eight cases of adult HIES were reported, and all the patients were male, aging 18 to 31 years. Prolonged disease course, recurrent infection and formation of cystic lesions in the lungs were important features of HIES. Early diagnosis and treatment with specific antibiotics were important for improving outcome of the patients. Conclusion: Refractory pulmonary cystic lesions can be the initial presentation in adult HIES. Understanding of the clinical characteristics of HIES will be helpful to avoid misdiagnosis and improve prognosis.

Moderate Maternal Energy Restriction During Gestation in Pigs Attenuates Fetal Skeletal Muscle Development Through Changing Myogenic Gene Expression and Myofiber Characteristics.

Maternal undernutrition during gestation influences the development of the fetus, thereby increasing the risk of metabolic syndrome in adulthood. Skeletal muscle, one of the key insulin-responsive organs, is susceptible to maternal nutritional programming. This study aimed to evaluate the effect of moderate maternal energy restriction during gestation in pigs on basic events of fetal skeletal myogenesis. Primiparous, purebred Meishan sows were fed a control (normal energy intake) or a low-energy (LE) diet from mating to day 90 of gestation. Biochemical characteristics, myogenic gene expression, and myofiber characteristics were assessed in longissimus dorsi (LD) muscle of fetuses on days 55 and 90 of gestation. Fetal weights, myofiber density, and fetal umbilical vein serum triiodothyronine (T3) concentration decreased in LE group on both days 55 and 90 of gestation. The expression and activity of creatine kinase, the messenger RNA (mRNA) expression of myosin heavy chain ( MYH/ MyHC) genes ( MYH2 and MYH4), concentration of muscular DNA and protein, and protein expression of fast-MyHC isoforms were reduced in LD muscle of LE fetuses on day 55 or 90 of gestation. Meanwhile, myogenic gene expression was reduced in LE fetuses on day 55 or 90 of gestation, indicating the downregulation of myogenesis. Additionally, the exposure to LE diet led to increased isocitrate dehydrogenase activity and slow MyHC (MYH7) mRNA expression on day 90 of gestation, suggesting the elevation of oxidative muscle metabolism. These findings suggest that moderate energy restriction during gestation attenuates fetal skeletal muscle development in pigs, resulting in the delay of skeletal muscle differentiation and maturity.

Oxidative stress in intrauterine growth retardation

Intrauterine growth retardation (IUGR) is the failure of the fetus to achieve his/her intrinsic growth potential, due to anatomical and/or functional disorders and diseases in the feto-placental-maternal unit. Fetal growth within the uterus is a complex biological event influenced by genetic, epigenetic, and environmental factors, as well as maternal nutrition. These factors impact on the size and functional capacity of the placenta, uteroplacental blood flows and transfer of nutrients and oxygen from mother to fetus. Oxidative stress can influence metabolic pathways that alter the epigenetic state (stable alterations of gene expression through DNA methylation and histone modifications) of the fetal genome. This may provide a molecular mechanism for the role of oxidative stress on fetal programming. IUGR results in significant perinatal and long-term complications, including the development of insulin resistance/metabolic syndrome in adulthood. By linking oxidative stress with dysregulation of specific target genes, we may be able to develop therapeutic strategies that protect against organ dysfunction in the programmed offspring.

Dietary intake in young adults born small or appropriate for gestational age: data from the Haguenau cohort

ObjectivesCompare the dietary intake of young adults born small for gestational age (SGA) versus those born appropriate for gestational age (AGA).DesignCross-sectional analysis.SettingData at the 8-year follow-up Haguenau cohort (France). Data...

Urinary bladder hypersensitivity and dysfunction in female mice following early life and adult stress

Early adverse events have been shown to increase the incidence of interstitial cystitis/painful bladder syndrome in adulthood. Despite high clinical relevance and reports of stress-related symptom exacerbation, animal models investigating the contribution of early life stress to female urological pain are lacking. We examined the impact of neonatal maternal separation (NMS) on bladder sensitivity and visceral neuroimmune status both prior-to, and following, water avoidance stress (WAS) in adult female mice. The visceromotor response to urinary bladder distension was increased at baseline and 8d post-WAS in NMS mice, while colorectal sensitivity was transiently increased 1d post-WAS only in naïve mice. Bladder micturition rate and output, but not fecal output, were also significantly increased following WAS in NMS mice. Changes in gene expression involved in regulating the stress response system were observed at baseline and following WAS in NMS mice, and WAS reduced serum corticosterone levels. Cytokine and growth factor mRNA levels in the bladder, and to a lesser extent in the colon, were significantly impacted by NMS and WAS. Peripheral mRNA levels of stress-responsive receptors were differentially influenced by early life and adult stress in bladder, but not colon, of naïve and NMS mice. Histological evidence of mast cell degranulation was increased in NMS bladder, while protein levels of protease activated receptor 2 (PAR2) and transient receptor potential ankyrin 1 (TRPA1) were increased by WAS. Together, this study provides new insight into mechanisms contributing to stress associated symptom onset or exacerbation in patients exposed to early life stress.

The dangerous link between childhood and adulthood predictors of obesity and metabolic syndrome

The purpose of this review is to evaluate whether some risk factors in childhood work as significant predictors of the development of obesity and the metabolic syndrome in adulthood. These factors include exposures to risk factors in the prenatal period, infancy and early childhood, as well as other socio-demographic variables. We searched articles of interest in PubMed using the following terms: 'predictors AND obesity OR Metabolic syndrome AND (children OR adolescents) AND (dyslipidemia OR type 2 diabetes OR atherosclerosis OR hypertension OR hypercholesterolemia OR cardiovascular disease)' AND genetic OR epigenetic. Maternal age, smoking and weight gain during pregnancy, parental body mass index, birth weight, childhood growth patterns (early rapid growth and early adiposity rebound), childhood obesity and the parents' employment have a role in early life. Furthermore, urbanization, unhealthy diets, increasingly sedentary lifestyles and genetic/epigenetic variants play a role in the persistence of obesity in adulthood. Health promotion programs/agencies should consider these factors as reasonable targets to reduce the risk of adult obesity. Moreover, it should be a clinical priority to correctly identify obese children who are already affected by metabolic comorbidities.

Dysregulation of sirtuins and key metabolic genes in skeletal muscle of pigs with spontaneous intrauterine growth restriction is associated with alterations of circulating IGF-1

Prenatal and early postnatal life determines future health, and intrauterine growth restriction (IUGR) – associated low birth weight predisposes to metabolic syndrome in adulthood. We hypothesize here that IUGR might induce hormonal and gene expression alterations predisposing to metabolic disease.Using a porcine model of spontaneous IUGR, we determined in utero (71, 112days post-conception) and early-postnatal (2days post-birth) IGF-1, insulin and leptin levels, and in parallel we investigated, in skeletal muscle, the developmental expression patterns of sirtuins and metabolic and signaling genes IRS1, GLUT4, HK2 and GAPDH.IUGR was associated with impaired IGF-1 plasmatic levels. Gene expression of sirtuin 1, 5, 6, 7, GLUT4 and HK2 exhibited significant correlations with gestational age or body weight. SIRT1 and HK2 expression displayed an age- and weight-dependent downregulation in controls, which was lost in IUGR pigs. Conversely, SIRT2 and GLUT4 were upregulated in IUGR pigs. Within the set of genes studied, we found a significant correlation between IGF-1 levels and gene expression in control, but not IUGR samples, indicating that lower IGF-1 may be a limiting factor in IUGR. IUGR-dependent gene alterations were partly linked to epigenetic changes on histone H3 acetylation and methylation.Overall, our data indicate that several sirtuins and metabolic genes display specific gene expression trajectories during fetal and early postnatal life. Gene expression alterations observed in IUGR are correlated to IGF-1 dysregulation. Given the importance of the genes studied in metabolic control, their perinatal alterations might contribute to the predisposition to metabolic disease of adulthood.

Lower body weight and BMI at birth were associated with early adiposity rebound in 21-hydroxylase deficiency patients.

21-hydroxylase deficiency (21-OHD) is the most common type of congenital adrenal hyperplasia. In addition to the clinical problems caused by adrenal insufficiency and androgen excess, a risk for obesity and metabolic syndrome during young adulthood is a major ramification of the disease. Although glucocorticoid therapy is very likely to be one of the contributory factors, the precise causes of the metabolic status of adult 21-OHD patients remain to be clarified. Previously we reported that 21-OHD patients developed early onset AR, a condition which might create a risk for obesity and metabolic syndrome in adulthood. In order to elucidate the association between the onset of AR and factors during the fetal period to early infancy, we conducted a retrospective longitudinal analysis of 29 21-OHD patients (male: 14 cases, female: 15 cases, salt wasting type: 16, simple virilizing type: 13), who were identified by newborn screening and followed up at least until the age 10 years. Body size at birth, lower body weight, and lower BMI were found to precipitate the timing of AR. On the other hand, no significant association was observed between the timing of AR and sex, gestational age, treatment regimen (including cumulative dose of HDC), and disease severity (the type of the disease, the value of DHEA-S and 17-OHP). There are two points to consider: first, in 21-OHD patients treated with glucocorticoid substitution therapy, the risk for early AR cannot be reduced by adjusting the dose of glucocorticoid; second, fetal factors might affect the metabolic status of 21-OHD patients.

Childhood Obesity and Hypertension

The epidemic of obesity along with hypertension (HTN) and cardiovascular disease is a growing contributor to global disease burden. The prevalence of HTN and pre-hypertension in children has been rising steadily over the decades to nearly 4% and 10% respectively [1,2]. Paediatric hypertension is one of the strongest predictor of adult hypertension, which increases the cardiovascular mortality risk in adults [3]. Obesity in childhood is found to be associated with hypertension, dyslipidemia, impaired glucose metabolism and other metabolic and physical consequences like left ventricular hypertrophy, nonalcoholic steatohepatitis, obstructive sleep apnea, orthopedic problems, and psychosocial problems. A literature review found that the risk of adult obesity is at least twice as high for obese children as for non-obese children, as about a third of obese preschool children were obese as adults, and about half of obese school-age children were obese as adults [4]. Adults who have been obese as children may have an even greater prevalence of risk factors for CVD, including hypertension and dyslipidemia, compared with those who had normal weight as children. It has also been shown that childhood obesity and central adiposity increased the risk for the metabolic syndrome in adulthood [5].

Erişkin Asperger Sendromu: Olgu sunumu

Asperger's Syndrome in adulthood: a case report Asperger's Syndrome (AS) is characterized by social deficits, communication difficulties, and stereotypical behaviors. Unlike autism, delays in language and cognitive development are not seen in Asperger's syndrome. AS is typically diagnosed in childhood, although some cases may be diagnosed in adulthood. Due to the clinical features of AS, diagnostically it can be confused with schizophrenia, anxiety disorders, obsessive-compulsive disorder, and personality disorders; hence, diagnosis of AS may be missed, especially in adulthood. This case is presented to emphasize the importance of adult AS, given that it is generally diagnosed in childhood, which leads to difficulties in diagnosis and differential diagnosis in adulthood if the condition has not been diagnosed in childhood.

Juvenile rheumatoid arthritis, endocrine arthropathy or hypermobility syndrome?

Оbjective. Evaluation of the frequency of detection of various associated diseases, including endocrine pathology in patients with a history of juvenile rheumatoid arthritis (JRA), which could affect the formation of joint syndrome in adulthood. An important task of the doctor-internist is the ability to differentiate articular syndrome in rheumatic arthropathies from joint damage due to many endocrine disorders, accompanied by a similar clinical picture.Materials and methods. 64 adult patients with history of JRA were examined in a rheumatological department of Alexander Hospital, Kyiv. Particular attention was paid to combination of rheumatic and endocrine diseases that may be accompanied by articular syndrome.Results and discussion. In 12.5% of patients with JRA in anamnesis endocrine pathology was found, in whom 4,7% of patients pituitary pathology was observed, including pituitary adenoma.Conclusions. The combination of rare diseases such as pituitary adenoma and JRA needs further study the impact of these diseases on the development of articular syndrome.

The famine exposure in early life and metabolic syndrome in adulthood

Epidemiologic studies have revealed that early-life conditions influence later risk of chronic diseases. We aimed to explore whether exposure to Chinese famine between 1959 and 1962 during fetal and childhood period was related with metabolic syndrome (MS) in adulthood. 6445 subjects from SPECT-China study were divided into fetal-exposed (1959-1962), childhood-exposed (1949-1958), adolescence/young adult-exposed (1921-1948), non-exposed (1963-1974) and non-exposed (after 1975). MS was defined by the International Diabetes Federation criteria. The prevalences of MS in the non-exposed (1963-1974), fetal and childhood-exposed were 16.4%, 20.1% and 19.1% in men and 13.5%, 23.7% and 33.5% in women, respectively. After adjustment for age, compared with non-exposed (1963-1974), fetal and childhood-exposed women had significantly higher prevalences of MS (P<0.05), but not in men. Famine exposure during the fetal period (OR 1.47, 95% CI 1.05, 2.07) and childhood (OR 1.80, 95% CI 1.22, 2.67) was associated with higher risk of MS in women after adjusting for age (both P<0.05). Further adjustments for age, smoking, rural/urban residence and economic status did not significantly attenuate this association. Exposure to famine in early life had sex-specific association with MS. It also suggests the adverse effects of malnutrition might extend beyond the 'first 1000 days' and last 9 years.

The Role of Maternal Dietary Proteins in Development of Metabolic Syndrome in Offspring.

The prevalence of metabolic syndrome and obesity has been increasing. Pre-natal environment has been suggested as a factor influencing the risk of metabolic syndrome in adulthood. Both observational and experimental studies showed that maternal diet is a major modifier of the development of regulatory systems in the offspring in utero and post-natally. Both protein content and source in maternal diet influence pre- and early post-natal development. High and low protein dams’ diets have detrimental effect on body weight, blood pressure191 and metabolic and intake regulatory systems in the offspring. Moreover, the role of the source of protein in a nutritionally adequate maternal diet in programming of food intake regulatory system, body weight, glucose metabolism and blood pressure in offspring is studied. However, underlying mechanisms are still elusive. The purpose of this review is to examine the current literature related to the role of proteins in maternal diets in development of characteristics of the metabolic syndrome in offspring.