Evaluation of a standardised protocol to measure the disease burden of respiratory syncytial virus infection in young children in primary care.

BACKGROUND: A better understanding of the burden of respiratory syncytial virus (RSV) infections in primary care is needed for policymakers to make informed decisions regarding new preventive measures and treatments. The aim of this study was to develop and evaluate a protocol for the standardised measurement of the disease burden of RSV infection in primary care in children aged < 5 years. METHODS: The standardised protocol was evaluated in Italy and the Netherlands during the 2019/20 winter. Children aged < 5 years who consulted their primary care physician, met the WHO acute respiratory infections (ARI) case definition, and had a laboratory confirmed positive test for RSV (RT-PCR) were included. RSV symptoms were collected at the time of swabbing. Health care use, duration of symptoms and socio-economic impact was measured 14 days after swabbing. Health related Quality of life (HRQoL) was measured using the parent-proxy report of the PedsQL™4.0 generic core scales (2-4 years) and PedsQL™4.0 infant scales (0-2 years) 30 days after swabbing. The standardised protocol was evaluated in terms of the feasibility of patient recruitment, data collection procedures and whether parents understood the questions. RESULTS: Children were recruited via a network of paediatricians in Italy and a sentinel influenza surveillance network of general practitioners in the Netherlands. In Italy and the Netherlands, 293 and 152 children were swabbed respectively, 119 and 32 tested RSV positive; for 119 and 12 children the Day-14 questionnaire was completed and for 116 and 11 the Day-30 questionnaire. In Italy, 33% of the children had persistent symptoms after 14 days and in the Netherlands this figure was 67%. Parents had no problems completing questions concerning health care use, duration of symptoms and socio-economic impact, however, they had some difficulties scoring the HRQoL of their young children. CONCLUSION: RSV symptoms are common after 14 days, and therefore, measuring disease burden outcomes like health care use, duration of symptoms, and socio-economic impact is also recommended at Day-30. The standardised protocol is suitable to measure the clinical and socio-economic disease burden of RSV in young children in primary care.

Classification of intellectual disability according to domains of adaptive functioning and between-domains discrepancy in adults with epilepsy.

BACKGROUND: In the Diagnostic and Statistical Manual of Mental Disorders-Fifth edition (DSM-5), the diagnostic criteria of intellectual disability (ID) include three domains of adaptive deficits: the conceptual, social and practical. Substantial intra-individual differences between domains can be considered an ID domain discrepancy. METHOD: We explored the associations between ID domains, discrepancies and epilepsy in 189 adults (mean age = 47.9; SD = 15.6). Each DSM-5 ID domain was assessed separately, using subscales of the Vineland II for the social and practical domains, and psychological instruments, including intelligence tests, for the conceptual domain. A set of standardised criteria is proposed to identify an ID domain discrepancy. RESULTS: An ID domain discrepancy seemed to be present in about one-third of subjects and was particularly present in subjects with moderate ID (53.4%). Impairment in the social domain was most often the reason for the discrepancy. The presence of a discrepancy was significantly related to a focal (localised) epilepsy type (OR = 2.3, P = .028) and a mixed seizure type (OR = 1.4, P = .009). Epilepsy characteristics that are indicative of a more severe and refractory epilepsy, including various seizure types, a high seizure frequency, a combined epilepsy type (both focal and generalised epilepsy) and an early age at onset, were significantly related to more severe impairments in conceptual, social and practical adaptive behaviour (all P values <.01). CONCLUSIONS: With a substantial proportion of the subjects who had both ID and epilepsy with an ID discrepancy, professionals should be aware of this and take all domains of ID into account when studying or working with this vulnerable population.

Diagnostic overshadowing in a population of children with neurological disabilities: A cross sectional descriptive study on acquired ADHD.

AIM: Diagnostic overshadowing refers to the underdiagnosis of comorbid conditions in children with known neurological diagnoses. To demonstrate diagnostic overshadowing we determined the prevalence of attention deficit-hyperactivity disorders (ADHD) in a cohort of children with a wide range of neurological disabilities. METHOD: The study cohort consisted of 685 children (mean age 10.3 years, SD: 3.1; 425 boys and 260 girls) who visited a tertiary outpatient multidisciplinary clinic for neurological learning disabilities. Patients with ADHD were identified by retrospective chart review using DSM-IV criteria. RESULTS: The prevalence of ADHD in this cohort was 38.8% (266 children); of these children only 28.2% (75 children) were diagnosed with ADHD before referral. INTERPRETATION: ADHD is a common problem in children with neurological disabilities and may be underdiagnosed due to overshadowing of somatic, physical or syndromal features of the disability. In our heterogeneous population ADHD was overshadowed in 71.8% of the cases. This finding may have important implications for diagnosis and treatment of mental health needs in children with neurological disabilities.

Temporalis muscle hypertrophy and reduced skull eccentricity in Duchenne muscular dystrophy.

Muscle hypertrophy and muscle weakness are well known in Duchenne muscular dystrophy. Decreased muscle force can have secondary effects on skeletal growth and development such as facial and dental morphology changes. In this study, we quantified temporal muscle thickness, circumference, and eccentricity of the skull and the head on T1-weighted magnetic resonance imaging (MRI) scans of the head of 15 Duchenne muscular dystrophy patients and 15 controls. Average temporal muscle thickness was significantly increased in patients (12.9 ± 5.2 mm) compared to controls (6.8 ± 1.4 mm) (P < .0001), whereas the shape of the skull was significantly rounder compared to controls. Temporal muscle thickness and skull eccentricity were significantly negatively correlated in patients, and positively in controls. Hypertrophy of the temporal muscles and changes in skull eccentricity appear to occur early in the course of Duchenne muscular dystrophy. Further studies in younger patients are needed to confirm a causal relationship.

Diagnostic and prognostic prediction models.

Risk prediction models can be used to estimate the probability of either having (diagnostic model) or developing a particular disease or outcome (prognostic model). In clinical practice, these models are used to inform patients and guide therapeutic management. Examples from the field of venous thrombo-embolism (VTE) include the Wells rule for patients suspected of deep venous thrombosis and pulmonary embolism, and more recently prediction rules to estimate the risk of recurrence after a first episode of unprovoked VTE. In this paper, the three phases that are recommended before a prediction model may be used in daily practice are described: development, validation, and impact assessment. In the development phase, the focus is on model development commonly using a multivariable logistic (diagnostic) or survival (prognostic) regression analysis. The performance of the developed model is expressed by discrimination, calibration and (re-) classification. In the validation phase, the developed model is tested in a new set of patients using these same performance measures. This is important, as model performance is commonly poorer in a new set of patients, e.g. due to case-mix or domain differences. Finally, in the impact phase the ability of a prediction model to actually guide patient management is evaluated. Whereas in the development and validation phase single cohort designs are preferred, this last phase asks for comparative designs, ideally randomized designs; therapeutic management and outcomes after using the prediction model is compared to a control group not using the model (e.g. usual care).

Normal variability of children's scaled scores on subtests of the Dutch Wechsler Preschool and Primary scale of Intelligence - third edition.

Intelligence tests are included in millions of assessments of children and adults each year (Watkins, Glutting, & Lei, 2007a , Applied Neuropsychology, 14, 13). Clinicians often interpret large amounts of subtest scatter, or large differences between the highest and lowest scaled subtest scores, on an intelligence test battery as an index for abnormality or cognitive impairment. The purpose of the present study is to characterize "normal" patterns of variability among subtests of the Dutch Wechsler Preschool and Primary Scale of Intelligence - Third Edition (WPPSI-III-NL; Wechsler, 2010 ). Therefore, the frequencies of WPPSI-III-NL scaled subtest scatter were reported for 1039 healthy children aged 4:0-7:11 years. Results indicated that large differences between highest and lowest scaled subtest scores (or subtest scatter) were common in this sample. Furthermore, degree of subtest scatter was related to: (a) the magnitude of the highest scaled subtest score, i.e., more scatter was seen in children with the highest WPPSI-III-NL scaled subtest scores, (b) Full Scale IQ (FSIQ) scores, i.e., higher FSIQ scores were associated with an increase in subtest scatter, and (c) sex differences, with boys showing a tendency to display more scatter than girls. In conclusion, viewing subtest scatter as an index for abnormality in WPPSI-III-NL scores is an oversimplification as this fails to recognize disparate subtest heterogeneity that occurs within a population of healthy children aged 4:0-7:11 years.

Ketogenic diet effects on cognition, mood, and psychosocial adjustment in children.

INTRODUCTION: The ketogenic diet (KD) is increasingly used for the treatment of refractory epilepsy. The aim of this study was to evaluate possible adverse effects of the diet on cognition, behavior, psychosocial adjustment, and quality of life in school-aged children and adolescents. METHOD: Fifteen subjects were assessed before diet initiation. After approximately 6 months, on diet treatment 11 patients (73%) were reassessed. We used a combination of individually administered psychological tests for the children and parent report questionnaires. RESULTS: Five of 15 patients had a seizure reduction of more than 50%. Cognition showed a small trend toward improvement in most patients. Psychosocial adjustment, on the other hand, showed small trends toward worsening. For mood, two areas showed a larger change, revealing more mood problems although this was not on a statistically significant level. CONCLUSION: In this small group of children, there is no indication that the KD has a negative impact on cognition or social adaptation at short term. There is a tendency toward an increase in mood problems.

Cognitive effects of interictal epileptiform discharges in children.

Frequent interictal epileptiform discharges (IEDs) may have effects on cognition. We analysed a group of 182 children with different epilepsy syndromes as well as children with IEDs without observed seizures [corrected], with 24-h ambulatory EEG and cognitive tests. The IED index was estimated, in wakefulness and in sleep, as percentage of time in five categories (0%, <1%, 1-10%, ≥10-50% and ≥50%). IEDs were defined as spikes or spike-wave complexes, isolated or occurring serially (in runs) without evident clinical signs of a seizure. The IED categories were correlated to cognitive test results and epilepsy characteristics. The group of patients with diurnal IEDs in ≥10% of the EEG record showed impaired central information processing speed, short-term verbal memory and visual-motor integration. This effect was seen independently from other EEG-related and epilepsy-related characteristics, and independently from epilepsy syndrome diagnosis. The impact of the nocturnal IEDs was of less importance; only contributing partially to the slowing of central information processing speed. We conclude that frequent IEDs (in more than 10% of the record) in the awake EEG can impair cognitive performance in children. Whether children with a high diurnal spike frequency and low seizure frequency can benefit from antiepileptic treatment should be examined in controlled trials.

Psychosocial adjustment in a Dutch sample of children with cerebral palsy.

BACKGROUND: Over the last couple of years, there has been increasing interest for QoL in children with CP. Psychosocial adjustment in these children remains underrepresented in current literature. AIMS: To describe psychosocial adjustment in children with CP by means of the Psychosocial Adjustment and Role Skills Scale III (PARS-III), to describe the psychometric properties of this questionnaire, to identify a cut-off score for psychosocial maladjustment and to investigate the relationship between patient characteristics (i.e. predictive factors) and psychosocial adjustment. METHODS: The parents of 93 children with CP (59 boys, 34 girls; mean age 12.3 years, SD 3.8; 4-18; GMFCS 1: 28, GMFCS 2: 5, GMFCS 3: 19, GMFCS 4: 18, GMFCS 5: 23) completed the PARS-III and the Child Behavior Checklist (CBCL) concerning the psychosocial and behavioral functioning of their child. RESULTS: Cronbach's alpha-coefficient for the PARS-III was 0.89 indicating good internal consistency. High correlation with the CBCL was found. Confirmatory factor analysis confirmed the 6 domain structure of the PARS-III. Overall, children with CP achieved lower psychosocial adjustment scores compared to healthy children. A cut-off score (1 SD below the mean) of 78 was found. When predicting psychosocial maladjustment in children with CP, less gross motor function, hand function, communication skills and bilateral involvement of CP are the most important factors, but these can only explain 36% of variation in psychosocial adjustment. CONCLUSION: Using the by-proxy version of the PARS-III it was found that children with CP are reported to achieve lower psychosocial adjustment scores than healthy children.

Impaired language performance as a precursor or consequence of Rolandic epilepsy?

OBJECTIVES: A correlation between language impairment and Rolandic epilepsy is frequently reported. It is unknown whether this language impairment develops gradually as a consequence of Rolandic epilepsy or precedes the onset of seizures. In the latter case both language impairment and Rolandic epilepsy may be symptoms of an underlying syndrome or both develop during the process of epileptogenesis. METHODS: Non-comparative clinical cohort study of 48 children with Rolandic epilepsy (children's mean age is 9 years, and 7 months; SD is 1 year, and 8 months). They were screened for previous and current language impairment and their reading skills were examined. RESULTS: 23% of children with Rolandic epilepsy had speech therapy in the past and 35% repeated a year on primary school, which is more often compared to the Dutch population of children. Their results on a reading task revealed lower scores. CONCLUSIONS: Language is impaired in children with Rolandic epilepsy. In some children this impairment of language may even be a precursor, for the Rolandic epilepsy. It is undecided however, whether the language impairment develops gradually after the onset of epilepsy, whether Rolandic epilepsy and language impairment are both symptoms of an underlying syndrome or both develop during the process of epileptogenesis as we observed in some children the onset of language impairment before the onset of epilepsy.

Nocturnal epileptiform EEG discharges, nocturnal epileptic seizures, and language impairments in children: review of the literature.

This review addresses the effect on language function of nocturnal epileptiform EEG discharges and nocturnal epileptic seizures in children. In clinical practice, language impairment is frequently reported in association with nocturnal epileptiform activity. Vice versa, nocturnal epileptiform EEG abnormalities are a common finding in children with specific language impairment. We suggest a spectrum that is characterized by nocturnal epileptiform activity and language impairment ranging from specific language impairment to rolandic epilepsy, nocturnal frontal lobe epilepsy, electrical status epilepticus of sleep, and Landau-Kleffner syndrome. In this spectrum, children with specific language impairment have the best outcome, and children with electrical status epilepticus of sleep or Landau-Kleffner syndrome, the worst. The exact nature of this relationship and the factors causing this spectrum are unknown. We suggest that nocturnal epileptiform EEG discharges and nocturnal epileptic seizures during development will cause or contribute to diseased neuronal networks involving language. The diseased neuronal networks are less efficient compared with normal neuronal networks. This disorganization may cause language impairments.

Psychogenic non-epileptic seizures--definition, etiology, treatment and prognostic issues: a critical review.

In this review we systematically assess our currently available knowledge about psychogenic non-epileptic seizures (PNES) with an emphasis on the psychological mechanisms that underlie PNES, possibilities for psychological treatment as well as prognosis. Relevant studies were identified by searching the electronic databases. Case reports were not considered. 93 papers were identified; 65 of which were studies. An open non-randomized design, comparing patients with PNES to patients with epilepsy is the dominant design. A working definition for PNES is proposed. With respect to psychological etiology, a heterogeneous set of factors have been identified. Not all factors have a similar impact, though. On the basis of this review we propose a model with several factors that may interact in both the development and prolongation of PNES. These factors involve psychological etiology, vulnerability, shaping, as well as triggering and prolongation factors. A necessary first step of intervention in patients with PNES seems to be explaining the diagnosis with care. Although the evidence for the efficacy of additional treatment strategies is limited, variants of cognitive (behavioural) therapy showed to be the preferred type of treatment for most patients. The exact choice of treatment should be based on individual differences in the underlying factors. Outcome can be measured in terms of seizure occurrence (frequency, severity), but other measures might be of greater importance for the patient. Prognosis is unclear but studies consistently report that 1/3rd to 1/4th of the patients become chronic.

Psychogenic non-epileptic seizures--diagnostic issues: a critical review.

In this review we systematically assess our current knowledge about psychogenic non-epileptic seizures (PNES), epidemiology, etiology, with an emphasis on the diagnostic issues. Relevant studies were identified by searching the electronic databases. Case reports were not considered. Articles were included when published after 1980 up till 2005 (26 years). A total of 84 papers were identified; 60 of which were actual studies. Most studies have serious methodological limitations. An open non-randomized design, comparing patients with PNES to patients with epilepsy is the dominant design. The incidence of PNES in the general population is low. However, a relatively high prevalence is seen in patients referred to epilepsy centres (15-30%). Caution is needed in the clinical interpretation of ictal features suggested to be pathognomic for PNES. Video-EEG is widely considered to be the gold standard for diagnosing PNES. Still the differential diagnosis epileptic/non-epileptic seizures can be difficult. Despite the current available technical facilities, the mean latency between onset of PNES and final diagnosis as being non-epileptic and psychogenic is approximately 7 years. One of the reasons for diagnostic delay is that the diagnosis of PNES is often limited to a 'negative' process and consequently PNES is characterized as a 'non-disease' (i.e. 'not epilepsy'). The psychological diagnosis is thus an important, although not a conclusive, 'second phase' aspect of medical decision making. Specific relations between seizure presentation and underlying psychological mechanisms are not conclusive. A classification between major motor manifestations and unresponsiveness is recognized. With respect to psychological etiology, a heterogeneous set of factors have been identified that may be involved in the causation, development and provocation of PNES.

Levetiracetam therapy for treatment of choreoathetosis in dyskinetic cerebral palsy.

Dyskinetic cerebral palsy (CP) is a movement disorder that is difficult to treat and which causes major disability. We report on two female patients (aged 5y and 8y) who experienced severe perinatal asphyxia and developed dyskinetic CP, clinically characterized by choreoathetosis. Neuropsychological testing of these children showed a low average developmental quotient and no attentional deficit. Monotherapy with levetiracetam was initiated to improve balance control and fine motor skills. Treatment was evaluated by use of video and the Visual Analog Scale. In both children an impressive improvement of balance control and fine motor skills was observed. No side effect occurred. Furthermore, both patients showed more interest and pleasure during activities according to their parents. In a recent multidisciplinary evaluation of the initiated therapy, the parents, the therapist, and the rehabilitation doctor all confirmed that the effect initially observed was still present at 14 and 26 months later. To our knowledge, this report on two patients with dyskinetic CP is the first suggesting that levetiracetam may offer an alternative to the standard therapy of involuntary, uncontrolled movements in this group of patients.

Cognitive functioning of adolescents and young adults with meningomyelocele and level of everyday physical activity.

PURPOSE: To explore whether cognitive functioning in patients with meningomyelocele (MMC) is related to level of everyday physical activity. METHOD: In a cross-sectional study in 14 patients with MMC (aged 14 - 26 years) a neuropsychological test battery was administered to each patient. Everyday physical activity of the patients was measured with an accelerometry-based Activity Monitor (AM), and compared to 14 healthy comparison subjects. RESULTS: Intellectual ability of 10 patients was in the normal range. For memory and verbal learning, executive functioning, divided attention and reaction speed subnormal scores were present in six or more patients. Time spent on dynamic activities was low in patients with MMC as compared to healthy subjects. After controlling for intellectual ability, we found that in patients with MMC (i) executive functioning was positively related, and (ii) word production was negatively related to everyday physical activity. CONCLUSION: We found some indication that specific impairments in executive functioning might be related to everyday physical activity of adolescents and young adults with MMC.

Long-term neuropsychological performance in a cohort of children and adolescents after severe paediatric traumatic brain injury.

OBJECTIVE: The purpose of the present study was to evaluate progress in neuropsychological performance in children and adolescents with severe paediatric traumatic brain injury (TBI), from admission to the rehabilitation centre up to 3-12 years after the trauma. METHODS: Children and adolescents (n = 31, mean age at injury 11.8 years, SD = 3.8; at follow-up 18.8 years; SD = 4.5) who all had suffered a TBI participated. A comprehensive neuropsychological test battery was administered at the start of rehabilitation (T1), around discharge (T2) and in the long-term (at least 3 years after rehabilitation; T3). T1 and T2 were clinical assessments; T3 was executed as a follow-up measurement for this study. RESULTS: At T1 and T2, most problems were in the domains of attention, memory and executive functioning. At the start of rehabilitation most deficits were with performal intelligence (61%); at discharge (mean length of stay 411 days) considerably less children had severe deficits on the intelligence domain (23%). At long-term follow-up, most problems were in the domains attention, mental speed and memory. From admission to discharge 42% of the children improved on two or more cognitive tests; from discharge to follow-up this percentage was 13%. CONCLUSIONS: In this unique study a clinical cohort of children with severe TBI was followed for many years after injury. Most cognitive deficits were found in the early phase of rehabilitation. Most children did improve on cognitive functioning (40%) during the first year after their injury, whereas at follow-up most children had not changed. At follow-up, more than half of the children (54%) attended a regular school or had a regular job, corresponding to their age and pre-morbid functioning.

Semantic category fluency versus initial letter fluency over 60 seconds as a measure of automatic and controlled processing in healthy school-aged children.

Verbal fluency was operationalized as the number of words produced in a restricted category (i.e., semantic category [SCF] and words beginning with a given letter [ILF]) in 60 seconds. Word production in the first 15 seconds of either type of fluency task was defined as a measure of automatic information processing, whereas word production in the remaining 45 seconds (in 15-second periods) was taken as a measure of controlled information processing. Data revealed that over 60 seconds healthy children aged 8.4-9.7 years (n = 91) produced significantly more words and less incorrect responses on the SCF task than on the ILF task. Although word production was a function of both type of task and time, it was highest in the initial time slice of either type of fluency and decreased as time on task increased. Finally, no sex differences were found for any measure of performance on either type of fluency task. In contrast, the level of occupational achievement of the caregiver (LOA) appeared to be a determinant of the child's performance on either type of fluency task, indicating that LOA affects higher-order processes, such as the automation of newly learned verbal skills and effortful processing.

Controlled visuomotor preparation deficits in attention-deficit/hyperactivity disorder.

To the best of the authors' knowledge, there are no published reports on visuomotor preparation in attention-deficit/hyperactivity disorder (ADHD). This is unfortunate, because research suggests that ADHD is an output-related deficit, and suboptimal execution of tasks may be the result of incomplete visuomotor preparation. The authors compared 19 children with ADHD with 124 healthy and 120 pathological controls in terms of their performance (speed, speed variability, and accuracy) on the finger precuing test, a test measuring (automatic and controlled) visuomotor preparation. The data implied that children with ADHD have an impaired ability to engage in effortful, controlled visuomotor preparation activities. Fast, automatic response preparation was not affected by ADHD. In addition, children with ADHD showed more variability in overall test performance than other children. No group differences were found in response accuracy.

Verbal fluency over time as a measure of automatic and controlled processing in children with ADHD.

The performance of ADHD children on semantic category fluency (SCF) versus initial letter fluency (ILF) tasks was examined. For each participant, word production was recorded for each 15-s time slice on each task. Performance on both fluency tasks was compared to test the hypothesis that children with ADHD are characterized by a performance deficit on the ILF task because performance on this task is less automated than performance on the SCF. Children classified with ADHD (N = 20) were compared to children with other psychopathology (N = 118) and healthy controls (N = 130). Results indicated that the groups could not be differentiated by the total number of words produced in 60 s in either fluency task. As hypothesized, a significant interaction of group by productivity over time by type of fluency task was found: ADHD children had more problems finding words in the first 15 s of the IFL than did children in the other two groups, and as compared with their performance on the SCF. Results were taken to indicate that children with ADHD symptoms show a delay in the development of automating skills for processing abstract verbal information.