Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by early impairment in social and communication domains and autonomic nervous system unbalance. This study evaluated ...heart rate (HR) as a possible indicator of stress response in children with ASD as compared to children with language disorder (LD). Twenty-four patients mean age = 42.62 months; SD = 8.14 months,12 with ASD (10 M/2F) and 12 with LD (8 M/4F) underwent clinical Leiter International Performance Scale-Revised, Autism Diagnostic Observation Schedule, second edition (ADOS-2) and physiological evaluation (HR monitoring) during five interactive activities, while wearing an HR measurement device. IQ (ASD:IQ = 103.33 ± 12.85 vs. LD:IQ = 111.00 ± 8.88, p = 0.103) and fluid reasoning on the Leiter-R Scale were within the normal range in all subjects. Increased HR during the third activity (ADOS-2 bubble play) significantly correlated with autistic symptoms (r = 0.415; p = 0.044), while correlations between ADOS-2 total score and HR during the first activity (ADOS-2 free play; r = 0.368; p = 0.077), second activity (Leiter-R figure ground subscale; r = 0.373, p = 0.073), and fifth activity (ADOS-2 anticipation of a routine with objects; r = 0.368; p = 0.076) did not quite reach statistical significance. Applying a linear regression model, we found that the ADOS-2 total score significantly influenced HR variations (p = 0.023). HR monitoring may provide a better understanding of the stress-provoking situations for children with ASD. Furthermore, it could help clinicians detect the impact of the stressful condition on the autistic core and adress treatment strategy.
Adult phenotype of KCNQ2 encephalopathy Boets, Stephanie; Johannesen, Katrine M; Destree, Anne ...
Journal of medical genetics,
06/2022, Letnik:
59, Številka:
6
Journal Article
Recenzirano
Odprti dostop
BackgroundPathogenic KCNQ2 variants are a frequent cause of developmental and epileptic encephalopathy.MethodsWe recruited 13 adults (between 18 years and 45 years of age) with KCNQ2 encephalopathy ...and reviewed their clinical, EEG, neuroimaging and treatment history.ResultsWhile most patients had daily seizures at seizure onset, seizure frequency declined or remitted during childhood and adulthood. The most common seizure type was tonic seizures (early) infancy, and tonic-clonic and focal impaired awareness seizures later in life. Ten individuals (77%) were seizure-free at last follow-up. In 38% of the individuals, earlier periods of seizure freedom lasting a minimum of 2 years followed by seizure recurrence had occurred. Of the 10 seizure-free patients, 4 were receiving a single antiseizure medication (ASM, carbamazepine, lamotrigine or levetiracetam), and 2 had stopped taking ASM. Intellectual disability (ID) ranged from mild to profound, with the majority (54%) of individuals in the severe category. At last contact, six individuals (46%) remained unable to walk independently, six (46%) had limb spasticity and four (31%) tetraparesis/tetraplegia. Six (46%) remained non-verbal, 10 (77%) had autistic features/autism, 4 (31%) exhibited aggressive behaviour and 4 (31%) destructive behaviour with self-injury. Four patients had visual problems, thought to be related to prematurity in one. Sleep problems were seen in six (46%) individuals.ConclusionSeizure frequency declines over the years and most patients are seizure-free in adulthood. Longer seizure-free periods followed by seizure recurrence are common during childhood and adolescence. Most adult patients have severe ID. Motor, language and behavioural problems are an issue of continuous concern.
The aim of the study was to explore the outcome of neurocognitive deficits and neuroimaging correlates in young adult early treated phenylketonuric (PKU) patients. We conducted a longitudinal study ...of 14 PKU patients that were assessed for IQ and neuropsychological functioning including executive functions (EF) over 14years of follow-up (age range at 1st and 2nd assessments were 7.8–13.5 and 22.2–27.7years, respectively). The IQ of all 14 PKU patients was within the normal range. With respect to the 1st assessment, mean IQ at follow-up did not decrease significantly. Compared to control subjects (n=14), mean IQ of patients was significantly lower (p=.0005). Throughout adolescence and early adulthood there was an improvement of neuropsychological functioning of PKU patients in spite of the relaxation of diet, however some deficits were still detectable when compared to controls. All patients that underwent a second MRI scan showed white matter alterations ranging from mild to severe which was correlated neither with IQ nor with EF scoring. Cognitive, neuropsychological and neuroimaging outcome was influenced from life-long and/or second decade of life metabolic control. Nevertheless patients' developmental trajectories were in some cases independent from metabolic control. Our results support the hypothesis of an individual vulnerability to phenylalanine. However, as long as individual factors that account for the vulnerability to Phe are not recognized, strict dietary control is recommended for all the patients also in the second decade of life.
•Adult ETPKU patients have lower than expected IQs.•ETPKU patients show improvement of neuropsychological functioning after adolescence.•All adult ETPKU patients disclose white matter alterations on brain MRI.•Neurocognitive and neuroimaging outcome is influenced from metabolic control.•Developmental trajectories are sometimes independent from metabolic control.
Phenylketonuria (PKU) is an inherited metabolic disease characterized by a defective conversion of phenylalanine (Phe) to tyrosine, potentially leading to Phe accumulation in the brain. Dietary ...restriction since birth has led to normal cognitive development. However, PKU patients can still develop cognitive or behavioral abnormalities and subtle neurological deficits. Despite the increasing evidence in the field, the assessment of neurocognitive, psychopathological, and neurological follow-up of PKU patients at different ages is still debated. The high interindividual variability in the cognitive outcome of PKU patients makes the specificity of the neurocognitive and behavioral assessment extremely challenging. In the present paper, a multidisciplinary panel of Italian PKU experts discussed different tools available for cognitive, psychopathological, and neurological assessment at different ages based on the existing literature and daily clinical practice. This study aims to provide evidence and a real-life-based framework for a specific clinical assessment of pediatric, adolescent, and adult patients affected by PKU.
Selective mutism (SM) is classified in DSM-5 as an anxiety disorder. The aim of the study was to investigate the psychological features of children with SM and their parental psychological profiles, ...compared to generalized anxiety disorder (GAD) children and their parents. The parents of 26 preschool children with SM and 32 with children with GAD filled out the child behavior check list for 1½–5 years (CBCL1½–5) and the symptom checklist-90-revised (SCL-90-R). Information about the children and their parents’ histories was collected through clinical interviews. Children with SM scored higher than children with GAD on the CBCL1½–5 withdrawn scale and lower on the attention problems, aggressive behavior, and externalizing problems scales. Mothers of children with SM scored higher on the SCL-90-R obsessive–compulsive subscale and Global Severity Index than mothers of children with GAD, while fathers of children with SM scored higher on the SCL-90-R Phobic Anxiety subscale and on the Global Severity Index than fathers of children with GAD. Parents of children with SM displayed a greater presence of stressful life events than parents of children with GAD. Data appeared to confirm that SM and GAD share a common anxious core, though some differences in the children’s psychological profiles and the parents’ history and personality emerged. Future research should focus on the role of external factors, such as parent–child relationship, in the development of SM.
Abstract
Inherited disorders of neurotransmitter metabolism are rare neurodevelopmental diseases presenting with movement disorders and global developmental delay. This study presents the results of ...the first standardized deep phenotyping approach and describes the clinical and biochemical presentation at disease onset as well as diagnostic approaches of 275 patients from the registry of the International Working Group on Neurotransmitter related Disorders. The results reveal an increased rate of prematurity, a high risk for being small for gestational age and for congenital microcephaly in some disorders. Age at diagnosis and the diagnostic delay are influenced by the diagnostic methods applied and by disease-specific symptoms. The timepoint of investigation was also a significant factor: delay to diagnosis has decreased in recent years, possibly due to novel diagnostic approaches or raised awareness. Although each disorder has a specific biochemical pattern, we observed confounding exceptions to the rule. The data provide comprehensive insights into the phenotypic spectrum of neurotransmitter disorders.
The objective was to deepen the understanding of the causes of individual variability in phenylketonuria (PKU) by investigating which metabolic variables are most important for predicting cognitive ...outcomes (Phe average vs Phe variation) and by assessing the risk of cognitive impairment associated with adopting a more relaxed approach to the diet than is currently recommended.
We analysed associations between metabolic and cognitive measures in a mixed sample of English and Italian early-treated adults with PKU (N = 56). Metabolic measures were collected through childhood, adolescence and adulthood; cognitive measures were collected in adulthood. Metabolic measures included average Phe levels (average of median values for each year in a given period) and average Phe variations (average yearly standard deviations). Cognition was measured with IQ and a battery of cognitive tasks.
Phe variation was as important, if not more important, than Phe average in predicting adult outcomes and contributed independently. Phe variation was particularly detrimental in childhood. Together, childhood Phe variation and adult Phe average predicted around 40% of the variation in cognitive scores. Poor cognitive scores (> 1 SD from controls) occurred almost exclusively in individuals with poor metabolic control and the risk of poor scores was about 30% higher in individuals with Phe values exceeding recommended thresholds.
Our results provide support for current European guidelines (average Phe value = < 360 μmol/l in childhood; = < 600 μmo/l from 12 years onwards), but they suggest an additional recommendation to maintain stable levels (possibly Phe SD = < 180 μmol/l throughout life).
We investigated the relationship between how well people with phenylketonuria control blood Phe throughout their life and their ability to carry out cognitive tasks in adulthood. We found that avoiding blood Phe peaks was as important if not more important that maintaining average low Phe levels. This was particularly essential in childhood. We also found that blood Phe levels above recommended European guidelines was associated with around 30% increase in the risk of poor cognitive outcomes.
Dietary treatment is the cornerstone of therapy for phenylketonuria (PKU), but adherence to low- phenylalanine diet progressively decreases after adolescence. We designed a survey to characterize the ...dietary habits of Italian adult PKU patients and to identify psychological factors influencing disease perception and adherence to diet. Participants to the survey (n = 111; response rate 94%) were asked to complete a structured questionnaire. Patients appeared to have an altered perception and awareness of the disease. About 40% of them did not consider PKU a disease and, despite declaring regular monitoring of phenylalanine levels (85%), nearly half of them reported a high plasma value over the last 6 months (>600 μmol/L, 48%) or were unable to specify it (31%). Adherence to PKU diet was unsatisfactory, with increased consumption of natural protein sources and reduced daily use of amino-acid supplements (<4–5 times/day in 82% patients). In addition to the intrinsic characteristics of AA formula (palatability, ease of use), the most important factor influencing their consumption was the increased social pressure associated with their use (55%). Plasma phenylalanine periodical measurements (61%) and examinations at metabolic centers (49%) were considered relevant for compliance to diet. In Italian adult PKU patients dietary management was found to be inadequate, likely due to inappropriate perception and knowledge of the disease, and lack of awareness of the negative impact of poor metabolic control in adult life. Clinicians should consider implementing more intense and tailored educational measures, as well as structured transitional care processes.
Background:
Generalized anxiety and oppositional defiant disorders are among the most common psychopathological disorders in pre-school children. We investigated the symptom rate and perception of ...the child's disorders in parents of preschool children with generalized anxiety disorder (GAD) or oppositional defiant disorder (ODD).
Methods:
The parents of preschool children (mean age 54.35 months, SD ± 11.60) with ODD, GAD, or typical development (TD) filled the Symptom Check List-90-Revised (SCL-90-R) and the Child Behavior Checklist- 1½−5 (CBCL 1½ 5). Parents and children's diagnoses were determined by clinical assessment.
Results:
The parents of children with ODD reported a symptoms rate higher than parents of children with GAD or TD on most of the SCL-90-R (Global Severity Index of mental distress,
p
= 0.010; Somatization,
p
= 0.002; Paranoid Ideation,
p
< 0.000; and Phobic Anxiety scales,
p
= 0.030).
Conclusions:
On the CBCL scales, the parents of the ODD group overestimated the children's problems, while parents of children with GAD reported mainly children's emotional difficulties. Parents of children with ODD seem to be psychologically more vulnerable than parents of children with GAD. Parenting programs might be tailored considering the child's diagnosis and family functioning.
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