ABSTRACT
Asparagine synthetase deficiency is a rare autosomal recessive neurometabolic disorder caused by mutations in the asparagine synthetase gene. It is characterized by congenital microcephaly, intellectual disability, progressive cerebral atrophy, and intractable seizures. A decrease in asparagine in CSF or plasma guides subsequent investigations in some cases, but normal values are described in other cases. Therefore, reaching a diagnosis is challenging and relies on exome sequencing. We report the case of a child with progressive microcephaly, irritability, startle reflexes, and jitteriness since birth. Focal clonic and myoclonic seizures, status epilepticus, and infantile spasms appeared in the first months of life. At first, the EEG showed multifocal epileptic activity which later turned into modified hypsarrhythmia and discontinuous activity. Brain MRI showed brain atrophy, a simplified gyral pattern, and poor myelination. Plasma asparagine levels were normal. Due to remote parental consanguinity, a study of contiguous regions of runs of homozygosity was performed, showing a 5-Mb region (chr7:95629078-100679007) including the asparagine synthetase gene. The molecular analysis of this gene led to identification of a novel homozygous missense mutation, c.761G>T(p.Gly254Val), in our patient. The peculiar electroclinical phenotype may lead to diagnostic suspicion and molecular analysis which may benefit genetic counselling. [Published with video sequence].
Subject(s)
Aspartate-Ammonia Ligase/deficiency , Brain Diseases/physiopathology , Intellectual Disability/physiopathology , Microcephaly/physiopathology , Atrophy/diagnosis , Atrophy/physiopathology , Brain Diseases/diagnosis , Brain Diseases/genetics , Electroencephalography/methods , Humans , Infant, Newborn , Intellectual Disability/diagnosis , Intellectual Disability/genetics , Male , Microcephaly/diagnosis , Microcephaly/genetics , Seizures/genetics , Seizures/physiopathologyABSTRACT
OBJECTIVE: To meta-analytically examine the trends and correlates of antipsychotic use in youth with mood disorders. METHODS: Systematic literature search without language restriction in PubMed/MEDLINE/PsycINFO from database inception through March 2015 using the following search terms: (antipsychotic* OR neuroleptic* OR "dopamine blocker*" OR antidopaminergic) AND (child* OR adolescen* OR pediatric OR youth) AND (prescription* OR prescrib* OR use OR utilization OR database OR pharmacoepidemiolog* OR frequency OR rate OR rates). Random effects meta-analysis and meta-regression analyses were conducted. STUDY SELECTION: Included were studies reporting on the frequency of (1) mood disorders in antipsychotic-treated youth (≤ 19 years) and (2) antipsychotic use in youth with mood disorders. DATA ABSTRACTION: Two independent investigators abstracted data on study, patient, and treatment characteristics. RESULTS: Forty-one studies were meta-analyzed (N = 518,919, mean ± SD age = 12.8 ± 1.8 years, males = 65.7%). Altogether, 24.2% of antipsychotic-treated youth had a mood disorder diagnosis (studies = 34, depression spectrum disorder = 10.9%, bipolar spectrum disorder = 13.6%). In longitudinal studies, the overall proportion increased significantly from 17.3% in 2000 (range, 1996-2009) to 24.5% in 2006 (range, 2004-2011) (odds ratio [OR] = 1.50; 95% confidence interval [CI], 1.26-1.79; P < .0001). This increase was driven entirely by bipolar spectrum diagnoses (2001 = 11.1%, 2006 = 16.3%, P < .0001), rather than depression spectrum diagnoses (2001 = 9.1%, 2007 = 9.2%, P = .77). Among youth with mood disorders (8 studies), 24.0% received antipsychotics (depression spectrum disorder = 4.6%; bipolar spectrum disorder = 44.0%). CONCLUSIONS: The proportion of youth with mood disorder diagnoses increased significantly among antipsychotic-treated youth, driven entirely by an increase in youth with bipolar spectrum disorders. Progress in understanding the reasons for these trends and for an evaluation of the appropriateness of the observed antipsychotic prescribing requires more detailed information than is available in traditional pharmacoepidemiologic databases.
Subject(s)
Antipsychotic Agents/therapeutic use , Mood Disorders/drug therapy , Adolescent , Antipsychotic Agents/adverse effects , Bipolar Disorder/diagnosis , Bipolar Disorder/drug therapy , Bipolar Disorder/epidemiology , Bipolar Disorder/psychology , Child , Cross-Sectional Studies , Drug Utilization/trends , Female , Humans , Longitudinal Studies , Male , Mood Disorders/diagnosis , Mood Disorders/epidemiology , Mood Disorders/psychology , Off-Label Use , Regression AnalysisABSTRACT
BACKGROUND: Although caregiver burden is relevant to the outcome for psychiatrically ill youth, most studies have focused on caregiver burden in the community or research settings. Therefore, we aimed at evaluating the subjective caregiver strain (SCS) at the time of presentation of youth to a pediatric psychiatric emergency room (PPER), assessing potential correlates to provide leads for improvements in formal support systems. METHODS: In this retrospective cohort study, the internalized, externalized, and total SCS were assessed in caregivers of youth <18 years of age consecutively evaluated at a PPER during a 1 year period using the Caregiver Strain Questionnaire. Sociodemographic and a broad range of clinical data were collected during the PPER visit using a 12-page semistructured institutional evaluation form. The Appropriateness of Pediatric Psychiatric Emergency Room Contact scale, incorporating acuity, severity and harm potential, was used to rate appropriateness of the visit. RESULTS: In caregivers of 444 youth, the internalized SCS was significantly higher than the externalized SCS (p < 0.001). Multivariable analyses indicated that higher total and externalized SCS were associated with disruptive behavior or substance abuse/dependent disorder diagnosis, presenting complaint of aggression, and discharge plan to the police. Higher total and internalized SCS were associated with lower child functioning, whereas total and internalized SCS were lower in adopted children. In addition, higher externalized SCS was associated with investigator-rated inappropriateness of the emergency visit, presenting complaint of defiance, and a lack of prior psychiatric ER visits. CONCLUSIONS: High levels of CS in PPER highlight the necessity to adhere to existing guidelines regarding the inclusion of caregivers' perceptions into comprehensive psychiatric assessments. The particularly high strain in caregivers of children with externalizing disorders and in families with low-functioning youth may need to prompt PPER staff to provide efficient information on appropriate treatment options for these children and on support facilities for the parents.
Subject(s)
Caregivers/psychology , Mental Disorders/psychology , Parents/psychology , Stress, Psychological/epidemiology , Adolescent , Child , Child, Preschool , Cohort Studies , Emergency Service, Hospital , Female , Guideline Adherence , Humans , Internal-External Control , Male , Mental Disorders/epidemiology , Practice Guidelines as Topic , Retrospective Studies , Surveys and QuestionnairesABSTRACT
OBJECTIVE: Although irritability and aggression are relevant treatment targets in autism spectrum disorders (ASDs) and intellectual disability (ID) that may prompt antipsychotic use, antipsychotic prescribing patterns in such youth have not been systematically reviewed. METHOD: We systematically searched PubMed/MEDLINE/PsycInfo until March 2015 for studies reporting data on the frequency of youth diagnosed with ASDs and/or ID among antipsychotic-treated youth, as well as antipsychotic use in youth with ASD/ID, conducting a meta-analysis and meta-regression analysis of potential moderators, including publication year, study time point, country, setting, sample size, age, sex, and race/ethnicity. RESULTS: A total of 39 studies were meta-analyzed (n = 365,449, age = 11.4 ± 6.2 years, males = 70.0% ± 10.0%). Among 27 studies (n = 273,139, age = 11.9 ± 8.0 years, males = 67.0% ± 12.9%) reporting on antipsychotic-treated youth, 9.5% (95% CI = 7.8%-11.5%) were diagnosed with ASD/ID. In 20 studies (n = 209,756) reporting data separately for ASD, 7.9% (95% CI = 6.2%-9.9%) had an ASD diagnosis. In 5 longitudinal studies, the proportion of antipsychotic-treated youth with ASD did not change significantly from 1996 to 2011 (6.7% to 5.8%, odds ratio = 0.9, 95% CI = 0.8-1.0, p =.17). However, later study time point moderated greater ASD/ID proportions (ß = 0.12, p < .00001). In 13 studies (n = 96,688, age = 9.8 ± 1.2 years, males = 78.6% ± 2.0%) reporting on antipsychotic use in ASD samples, 17.5% (95% CI = 13.7%-22.1%) received antipsychotics. Again, later study time point moderated higher antipsychotic use among patients with ASD (ß = 0.10, p = .004). CONCLUSION: Almost 1 in 10 antipsychotic-treated youth were diagnosed with ASD and/or ID, and 1 in 6 youth with ASD received antipsychotics. Both proportions increased in later years; however, clinical reasons and outcomes of antipsychotic use in ASD/ID require further study.
Subject(s)
Antipsychotic Agents/therapeutic use , Autism Spectrum Disorder/drug therapy , Drug Prescriptions/statistics & numerical data , Intellectual Disability/drug therapy , Practice Patterns, Physicians'/statistics & numerical data , Adolescent , Child , Child, Preschool , Humans , Practice Patterns, Physicians'/trendsABSTRACT
BACKGROUND: The quality of general movements (GMs) and its predictive value have never been evaluated in late-preterm (LP) infants. AIMS: To determine the characteristics of GMs and their predictive value for neurodevelopmental outcome in a cohort of infants born between 34 and 36 weeks' gestation. STUDY DESIGN AND SUBJECTS: 574 LP infants were examined using the standard methodological principles of Prechtl's method for assessing GMs both during writhing and fidgety periods. OUTCOME MEASURES: Infants were assessed at 2 years of age with neuromotor and developmental scales. RESULTS: A significant correlation was found between GMs and outcome both at writhing (rs 0.68; p < 0.001) and at fidgety age (rs 0.78; p < 0.001). The assessment at 1 month showed 100% sensitivity and 86% specificity of predicting the development of cerebral palsy (CP), that at 3 months was 100% sensitivity and 97% specificity. CONCLUSIONS: During the fidgety age GMs predict CP with very high sensitivity and specificity. The qualitative assessment of GMs should be employed to help identify LP infants who require early intervention for neurological abnormalities.
Subject(s)
Cerebral Palsy/diagnosis , Child Development/physiology , Infant, Premature/physiology , Movement/physiology , Age Factors , Child, Preschool , Humans , Infant, Newborn , Italy , Predictive Value of Tests , Sensitivity and SpecificityABSTRACT
OBJECTIVES: Adolescence is a tough age for patients with inflammatory bowel disease (IBD) because they transition from child to adult medicine. Although a better understanding of the experience of illness and therefore a better response to the patient's needs have often been stressed, no studies have yet investigated the paediatricians' insight into their IBD adolescent patients. METHODS: A group of adolescents (ages 12-19) diagnosed as having IBD was administered a questionnaire listing 22 items of concern. They were asked to rank each item on a 5-point scale according to the degree of effect on the quality of their everyday life. The same questionnaire was administered to a group of paediatricians experienced in treating IBD and to a group of paediatric residents. Paediatricians and residents were asked to estimate how much each item would affect the quality of an average patient's life, according to the same scale. The questionnaire was also used in a face-to-face approach, asking a paediatrician to apply the estimation to an individual patient, instead of an average imaginary one. RESULTS: Fifteen paediatric gastroenterologists, 11 paediatric residents, and 28 patients (female:male = 16:12; median age 16.3 years) took part in the study. The majority of patients experienced Crohn disease (17 vs 11 with ulcerative colitis). We found only 6 items overlapping when comparing the top 10 items ranked by patients and paediatricians. The patients' number 1 concern occupies the ninth position in the paediatricians' list. The number 1 item for paediatricians is not even mentioned in the patients' top 10 list. Overall, both paediatricians' and residents' rankings were significantly higher than those given by patients. CONCLUSIONS: We found a significant misalignment in the estimation of health concerns between IBD adolescent patients and their paediatricians. A better insight into IBD patients' worries and concerns is crucial for the improvement of the patient's quality of life and disease outcome.