Cognition in children and young adults with myoclonus dystonia – A case control study

IntroductionIn adult patients with myoclonus dystonia (MD), cognitive deficits regarding information processing speed and executive functioning have been demonstrated, but it is unclear whether cognition is also affected in young MD patients. The present study investigates cognition in young MD patients and the role of an SGCE mutation.MethodsIn this case control study 20 young MD patients (9 children (5.75–12.58 years) and 11 adolescents/young adults (13.5–25.42 years)) were included and compared to an age-, IQ- and gender-matched healthy control group (n = 40). Within the patient group, we compared patients with (n = 12) and without (n = 8) an SGCE mutation (SGCE+/-). All participants completed neuropsychological tests for memory, attention/processing speed, executive functioning, social cognition and language.ResultsOverall, patients performed in the (low) average range, comparable to healthy controls. Only on a semantic fluency test, patients scored significantly lower. SGCE + patients had lower emotion recognition scores (a social cognition test) compared to SGCE-patients.ConclusionWe could not demonstrate cognitive deficits as found in adult MD patients in our younger group. Patients performed on the same level as healthy controls, with only a small difference in semantic fluency. We did not find executive deficits that were manifest in adult SGCE + patients, but we did find an association of an SGCE mutation and lower scores on a social cognition test. Similar to executive functioning, social cognition is a prefrontally regulated function, but had not been tested in adult MD. Hence, social cognition may precede executive problems in adulthood, suggesting growing into deficit.     

Neuropsychological functioning in adolescents and young adults with major depressive disorder – A review

While neuropsychological dysfunction is a contributor to major depressive disorder (MDD) in adult MDD, little is known about neuropsychological function in MDD during adolescence and early adulthood. The aim of this review is to evaluate literature on neuropsychological function in this young age group. A database search of Medline, the Cochrane database and PsycInfo was conducted. Inclusion/exclusion criteria yielded seven case-control studies on neuropsychological functioning in MDD (12–25 years of age) published since 1995. Effect sizes were calculated. Results show a broader range of statistically significant neuropsychological deficits in MDD compared to controls in the cognitive domains of executive function (EF), working memory (WM), psychomotor and processing speed (PPS), verbal fluency (VF) and visual (-spatial) memory (VM). Most convincingly, three out of four studies investigating WM and three out of four studies investigating PPS found statistically significant impairments in MDD with varying effect sizes. EF deficits were reported only in three out of seven studies with small, medium and large effect sizes. While some evidence was found for impaired VM and VF, no evidence was observed for attention and verbal learning and memory; however, these domains have been less extensively studied. Further research is required to broaden the study base.     

Deficits in the covert orienting of attention in children with Developmental Coordination Disorder: Does severity of DCD count?

Children with Developmental Coordination Disorder (DCD) show deficits in the covert orienting of visuospatial attention, suggesting an underlying issue in attentional disengagement and/or inhibitory control. However, an important theoretical issue that remains unclear is whether the pattern of deficits varies with DCD severity. Fifty-one children with moderate DCD (MDCD), 24 children with severe DCD (SDCD), and 38 typically developing (TD) children participated in the study. Their performance was compared on the covert orienting of visuospatial attention task (COVAT), specifically the voluntary control mode. Results showed that the pattern of performance differed between groups. At a short stimulus-response asynchrony (350 ms), the difference in response times for validly and invalidly cued trials was similar for all three groups. However, at the longer SOA (800 ms), both DCD groups continued to show a relative disadvantage for responses that followed invalid cues. This suggests that a deficit in response inhibition and/or attentional disengagement is manifest in children with both moderate and severe DCD. The implications of these findings for theory and treatment are discussed.     

Executive functions in preschool children with cerebral palsy – Assessment and early intervention – A pilot study

Objective: To assess the level of executive functioning among preschool children with cerebral palsy (CP) and evaluate effects of the Program Intensified habilitation (PIH). Methods: In this non-randomized, prospective study, 15 preschool children with CP, and their parents attended the PIH for a 1-year period. Executive functions were evaluated using the Behavior Rating Inventory of Executive functions – Preschool version (BRIEF-P), filled out by parents and preschool teachers. Results: Before PIH, scores of executive function difficulties were close to the general population mean. After PIH, fathers and preschool teachers reported reduced levels of executive difficulties on, respectively, the Emergent Metacognition Index and the Flexibility Index on the BRIEF-P. Mothers reported no changes. Conclusion: The children in our sample showed age-appropriate levels of executive functions before attending PIH. Some aspects of executive skills difficulties were reduced after PIH. Using BRIEF-P contributed to the differentiation of cognitive strengths and weaknesses among the children.     

Shared Features or Co-occurrence? Evaluating Symptoms of Developmental Coordination Disorder in Children and Adolescents with Autism Spectrum Disorder

Journal of Autism and Developmental Disorders - Motor differences are common in Autism Spectrum Disorder (ASD), but rarely evaluated against diagnostic criteria for Developmental Coordination...     

Developmental aspects of fear generalization – A MEG study on neurocognitive correlates in adolescents versus adults

BackgroundFear generalization is pivotal for the survival-promoting avoidance of potential danger, but, if too pronounced, it promotes pathological anxiety. Similar to adult patients with anxiety disorders, healthy children tend to show overgeneralized fear responses.ObjectiveThis study aims to investigate neuro-developmental aspects of fear generalization in adolescence – a critical age for the development of anxiety disorders.MethodsWe compared healthy adolescents (14–17 years) with healthy adults (19–34 years) regarding their fear responses towards tilted Gabor gratings (conditioned stimuli, CS; and slightly differently titled generalization stimuli, GS). In the conditioning phase, CS were paired (CS+) or remained unpaired (CS-) with an aversive stimulus (unconditioned stimuli, US). In the test phase, behavioral, peripheral and neural responses to CS and GS were captured by fear- and UCS expectancy ratings, a perceptual discrimination task, pupil dilation and source estimations of event-related magnetic fields.ResultsClosely resembling adults, adolescents showed robust generalization gradients of fear ratings, pupil dilation, and estimated neural source activity. However, in the UCS expectancy ratings, adolescents revealed shallower generalization gradients indicating overgeneralization. Moreover, adolescents showed stronger visual cortical activity after as compared to before conditioning to all stimuli.ConclusionVarious aspects of fear learning and generalization appear to be mature in healthy adolescents. Yet, cognitive aspects might show a slower course of development.     

The impact of the ketogenic diet on arterial morphology and endothelial function in children and young adults with epilepsy: A case–control study

PurposeThe present study aimed to assess the impact of the ketogenic diet on arterial morphology and endothelial function of the big vessels of the neck and on cardiac diastolic function, in a cohort of epileptic children and young adults treated with the ketogenic diet.MethodsPatients were recruited based on the following inclusion criteria: (1) patients who were or had been on the ketogenic diet for a time period of at least six months. Each patient underwent measurement of carotid intima media thickness, carotid artery stiffness, echocardiography, and diastolic function assessment. Patients with drug resistant epilepsy, matched for number, age and sex and never treated with ketogenic diet, were recruited as controls.ResultsThe population study was composed by 43 epilepsy patients (23 males), aged between 19 months and 31 years (mean 11 years). Twenty-three patients were or had been treated with ketogenic diet, and 20 had never been on it (control group). Subjects treated with the ketogenic diet had higher arterial stiffness parameters, including AIx and β-index and higher serum levels of cholesterol or triglycerides compared to those who had never been on the diet (control group) (p < 0.001).ConclusionsArterial stiffness is increased in children and young adults treated with the ketogenic diet, before the increase of the intima media thickness. This supports that arterial stiffness is an early marker of vascular damage.     

Effectiveness and tolerability of rufinamide in children and young adults with Lennox–Gastaut syndrome: A single center study in Korea

Purpose

Rufinamide is a novel antiepileptic drug (AED), which is known to be effective in the treatment of partial seizures and drop attacks in patients with Lennox–Gastaut syndrome (LGS). The aim of this study is to evaluate the efficacy and tolerability of rufinamide in those with LGS.

Methods

Patients with LGS who had received rufinamide adjunctive therapy were enrolled in this study. We retrospectively reviewed these patient's baseline clinical characteristics, and the reduction of seizure frequency and adverse events after the use of rufinamide.

Results

Twenty-three patients (15 males and 8 females, ages 4–22 years) were enrolled in the study. All the patients suffered from daily head drops and tonic seizures despite multiple antiepileptic drugs. After one month of rufinamide, one patient (4.3%) achieved freedom from seizures, ten (43.5%) achieved a ≥50% decrease in seizure frequency. After six months of rufinamide, eight patients (34.8%) maintained a satisfactory response (seizure free in one, and greater than 50% seizure reduction in seven). Adverse events were reported in six (26.0%) patients, which were somnolence in three, aggressive behavior in two, and aggravation of seizure in one patient.

Conclusions

Our results suggest that rufinamide is effective and safe in children and young adults with LGS.     

Orthostatic hypotension and attention in Parkinson’s disease with and without dementia

Summary. To compare frequency and degree of orthostatic hypotension (OH) in Parkinson’s disease (PD) and Parkinson’s disease with dementia (PDD) and its effect on attention and word fluency, blood pressure (BP) and heart rate changes during tilt were determined in 10 PD and 8 PDD patients. Attention and word fluency were evaluated in supine and tilted position using standard neuropsychological tests. OH defined as systolic BP (SBP) drop of ≥20 mmHg and/or diastolic BP (DBP) drop of ≥10 mmHg was present in 5 PDD patients and in 2 PD patients. SBP drop was significantly greater in PDD than in PD patients (P < 0.05). Whereas word fluency was unaffected by tilt in both patient groups, attention as assessed with the Test of Everyday Attention (TEA) deteriorated significantly in the PDD group, correlating with blood pressure response (ΔSBP and TEA-2, r = 0.828, P < 0.05; ΔDBP and TEA-2, r = 0.828, P < 0.05). We conclude that OH is frequent in PDD and should be addressed therapeutically since it may exacerbate attentional dysfunction.     

The use of EEG in Alzheimer’s disease,with and without scopolamine – A pilot study

ObjectiveTo use multivariate statistical analysis of EEG data in order to separate EEGs of patients with Alzheimer’s disease (AD) from controls. A group of individuals with mild cognitive impairment (MCI) was evaluated using the same methodology. Additionally, the effects of scopolamine on this separation are studied.MethodsStatistical pattern recognition (SPR) is used in conjunction with information extracted from EEGs before and after administration of scopolamine.ResultsThere was complete separation of the AD group and controls before administration of scopolamine. The separation increased after scopolamine had been given. Of the 10 MCI individuals, five seemed to belong to the AD group. Three of those progressed to AD within 1 year and one after 3 years.ConclusionsUsing SPR on EEG recordings it is possible to separate AD from controls. This separation can be increased by the use of scopolamine but the medication is not a prerequisite for classification. The results indicate that SPR is useful for predicting progress of MCI to AD.SignificanceEEG registration is a simple and noninvasive method. If these results are confirmed in other studies, this method could be more widely applied than the highly specialized methods used today in detection of early AD.     

Peripheral polyneuropathy in children and young adults with ataxia–telangiectasia

Background and purpose

Ataxia–telangiectasia (A-T) is a rare, autosomal recessive, multisystem disorder that leads to progressive neurodegeneration with cerebellar ataxia and peripheral polyneuropathy. Cerebellar neurodegeneration is well described in A-T. However, peripheral nervous system involvement is an underdiagnosed but important additional target for supportive and systemic therapies. The aim of this study was to conduct neurophysiological measurements to assess peripheral neurodegeneration and the development of age-dependent neuropathy in A-T.

Methods

In this prospective study, 42 classical A-T patients were assessed. The motor and sensory nerve conduction of the median and tibial nerves was evaluated. Data were compared to published standard values and a healthy age- and gender-matched control group of 23 participants. Ataxia scores (Klockgether, Scale for the Assessment and Rating of Ataxia) were also assessed.

Results

In A-T, neurophysiological assessment revealed neuropathic changes as early as the first year of life. Subjective symptomatology of neuropathy is rarely described. In the upper extremities, motor neuropathy was predominantly that of a demyelinating type and sensory neuropathy was predominantly that of a mixed type. In the lower extremities, motor and sensory neuropathy was predominantly that of a mixed type. We found significant correlations between age and the development of motor and sensory polyneuropathy in A-T compared with healthy controls (p < 0.001).

Conclusions

In A-T, polyneuropathy occurs mostly subclinically as early as the first year of life. The current study of a large national A-T cohort demonstrates that development of neuropathy in A-T differs in the upper and lower extremities.     

A perceptual and electropalatographic study of /∫/ in young people with Down's syndrome

Speech production in young people with Down's syndrome has been found to be variable and inconsistent. Errors tend to be more in the production of sounds that typically develop later, for example, fricatives and affricates, rather than stops and nasals. It has been suggested that inconsistency in production is a result of a motor speech deficit. Late acquired fricatives such as /s/ and /∫/ are complex articulations, which may require more precise motor programming and may therefore show highly inconsistent productions. Other factors potentially affecting speech production in this population are abnormal palatal structure, hearing loss, and hypotonia. A group of 20 young people with Down's syndrome were recorded using Electropalatography (EPG), reading a wordlist containing the phrase ‘a sheep’. The wordlist contained seven other phrases and was repeated 10 times. Eight typically developing, cognitively matched children and eight adults were also recorded producing the same data set. Articulatory (EPG pattern analysis) and perceptual analyses of the 10 productions of /∫/ were carried out. /∫/ production was found to be inconsistent in the young people with Down's syndrome, with more errors both in the auditory analysis and articulatory analysis than in the typical sample, which may be due to a motor programming or motor control problem. There were a greater number of errors in the EPG analysis than in the perceptual analysis. This suggests that some young people with DS were able to produce perceptually acceptable /∫/ with atypical EPG patterns. The use of typical, adult-modelled /∫/ EPG patterns in therapy may be inappropriate for some children with DS who present with atypical palatal structures.     

Do executive function deficits differentiate between children with Attention Deficit Hyperactivity Disorder (ADHD) and ADHD comorbid with Oppositional Defiant Disorder? A cross-cultural study using performance-based tests and the Behavior Rating Inventory of Executive Function

This study examined the differential executive dysfunction of children with attention deficit hyperactivity disorder (ADHD) and those with ADHD and oppositional defiant disorder (ODD) in Han Chinese. A total of 258 children (89 ADHD, 53 ADHD + ODD, 116 controls) completed performance-based executive function tests and had their everyday life executive skills rated by their parents using the Behavior Rating Inventory of Executive Function (BRIEF). Both the ADHD and ADHD + ODD groups performed worse than the controls in the Stroop and Trail-making tests and the BRIEF. The ADHD + ODD group were rated worse than the ADHD group on the BRIEF, but the two groups showed no significant difference in the performance-based tests. These findings suggest Han Chinese children with ADHD display executive dysfunction in performance-based tests and everyday life scenarios, in a similar way to findings in Western counterparts. However, children with ADHD + ODD showed more severe executive dysfunction in everyday life scenarios than those with ADHD only.     

Executive dysfunction in medication-naïve children with ADHD: A multi-modal fNIRS and EEG study

ObjectiveChildren with attention deficit hyperactivity disorder (ADHD) exhibit deficits in executive function. Since there are no clear biomarkers for the disorder, this study aimed to investigate the neurophysiological biomarkers for deficits in executive function in children with ADHD using functional near-infrared spectroscopy (fNIRS) and electroencephalography.MethodsTwenty patients diagnosed with ADHD and 19 typically developing children (TDC; 8–11 years old) were included. Event related potentials (ERPs) were recorded using an electroencephalogram (EEG) and oxygenated hemoglobin concentrations (Oxy-Hb) were recorded using fNIRS during a colored Go/NoGo task, simultaneously. Latencies and amplitudes of NoGo-N2 and NoGo/Go-P3 tasks were measured using EEG.ResultsChildren with ADHD showed significantly decreased Oxy-Hb in the right frontal cortex as well as longer NoGo-P3 latencies and a decreased NoGo/Go-P3 amplitude. There was a significant positive correlation between the Oxy-Hb and NoGo/Go-P3 amplitude.ConclusionsThese results suggest that children with ADHD experience executive dysfunction. Hemodynamic and electrophysiological findings during the Go/NoGo task might be useful as a biomarker of executive function.SignificanceThese findings have key implications for understanding the pathophysiology of deficits in executive function in ADHD.     

Sex differences of ischemic stroke in young adults—A single-center Chinese cohort study

Background and ObjectiveStroke at a young age is a societal challenge with a rising incidence. Our aim was to investigate sex differences in risk factors, etiology, and diagnostic process of ischemic stroke in Chinese young adults.MethodsWe retrospectively recruited 411 consecutive patients with first-ever ischemic stroke who were 18 to 50 years of age (mean age, 38.2 ± 8.1 years, women 31.4%), admitted to Peking Union Medical College Hospital from 2007 to 2018. Sex differences in demographics, risk factors, etiology, and diagnostic testing were analyzed.ResultsFemales were significantly younger than males (36.9 versus 38.7 years, P<0.05). Hypertension (43.0%), smoking (41.1%), hyperlipidemia (37.2%), and hyperhomocysteinemia (27.9%) were common risk factors, statistically higher among males than females (P<0.05). Stroke etiology showed a significant sex difference that large-artery atherosclerosis and small-vessel diseases were more common among males than females (48.6% versus 19.4%, P<0.001; 9.9% versus 3.1%, P<0.05, respectively). Stroke of other determined etiology was more common among females (50.4% versus 19.1%, P<0.001). Relevant abnormality rates were higher among females on screening for autoimmune diseases and thrombophilia (23.3% versus 11.1%, P<0.05 and 50.0% versus 16.7%, P<0.001, respectively).ConclusionsA high rate of the traditional stroke risk factors and etiological subtype of large artery atherosclerosis in males were found, as well as prominent sex differences in relevant diagnostic testing abnormality rates, providing useful information for developing sex-specific strategies in stroke evaluation and prevention in young adults.