Long-term forgetting is independent of age in healthy children and adolescents.

Introduction: In clinical neuropsychology, the phenomenon of accelerated long-term forgetting (ALF) has advanced to be a marker for subtle but clinically relevant memory problems associated with a range of neurological conditions. The normal developmental trajectory of long-term memory, in this case, memory recall after 1 week, and the influence of cognitive variables such as intelligence have not extensively been described, which is a drawback for the use of accelerated long-term forgetting measures in pediatric neuropsychology. Methods: In this clinical observation study, we analyzed the normal developmental trajectory of verbal memory recall after 1 week in healthy children and adolescents. We hypothesized that 1-week recall and 1-week forgetting would be age-dependent and correlate with other cognitive functions such as intelligence and working memory. Sixty-three healthy participants between the ages of 8 and 16 years completed a newly developed auditory verbal learning test (WoMBAT) and the WISC-V intelligence test (General Ability Index, GAI). Using these tests, 1 week recall and 1 week forgetting have been studied in relation to GAI, verbal learning performance, and verbal working memory. Results: Neither 1-week recall nor 1-week forgetting seems to be age-dependent. They are also not significantly predicted by other cognitive functions such as GAI or working memory. Instead, the ability to recall a previously memorized word list after 7 days seems to depend solely on the initial learning capacity. Conclusion: In the clinical setting, this finding can help interpret difficulties in free recall after 7 days or more since they can probably not be attributed to young age or low intelligence.

Impaired episodic verbal memory recall after 1 week and elevated forgetting in children after mild traumatic brain injury - results from a short-term longitudinal study.

Objective: There is preliminary evidence that children after traumatic brain injury (TBI) have accelerated long-term forgetting (ALF), i.e., an adequate learning and memory performance in standardized memory tests, but an excessive rate of forgetting over delays of days or weeks. The main aim of this study was to investigate episodic memory performance, including delayed retrieval 1 week after learning, in children after mild TBI (mTBI). Methods: This prospective study with two time-points (T1: 1 week after injury and T2: 3-6 months after injury), included data of 64 children after mTBI and 57 healthy control children aged between 8 and 16 years. We assessed episodic learning and memory using an auditory word learning test and compared executive functions (interference control, working memory, semantic fluency and flexibility) and divided attention between groups. We explored correlations between memory performance and executive functions. Furthermore, we examined predictive factors for delayed memory retrieval 1 week after learning as well as for forgetting over time. Results: Compared to healthy controls, patients showed an impaired delayed recall and recognition performance 3-6 months after injury. Executive functions, but not divided attention, were reduced in children after mTBI. Furthermore, parents rated episodic memory as impaired 3-6 months after injury. Additionally, verbal learning and group, but not executive functions, were predictive for delayed recall performance at both time-points, whereas forgetting was predicted by group. Discussion: Delayed recall and forgetting over time were significantly different between groups, both post-acutely and in the chronic phase after pediatric mTBI, even in a very mildly injured patient sample. Delayed memory performance should be included in clinical evaluations of episodic memory and further research is needed to understand the mechanisms of ALF.

Different trajectories of post-concussive symptom subscales after pediatric mild traumatic brain injury: Data from a prospective longitudinal study.

PURPOSE: The aim of this study was to investigate the trajectory of parent-rated post-concussive symptoms (PCS), attentional performance and participation within 6 months in children after mild traumatic brain injury (mTBI). METHODS: For this prospective longitudinal study, we included data on 64 children after mTBI and 57 healthy control children (age 8-16 years). Parents rated PCS using the Post-Concussion Symptom Inventory (PCSI) immediately (T0), 1 week (T1), and 3-6 months after injury (T2). Attentional performance (alertness, selective and divided attention) was measured using the Test of Attentional Performance (TAP) at T1 and T2 and participation was measured using the Child and Adolescent Scale of Participation (CASP) at T2. RESULTS: Friedman tests showed different trajectories of PCS subscales over time: Compared to pre-injury level, the amount of somatic and cognitive PCS was still elevated at T1, while emotional PCS at T1 were already comparable to pre-injury level. The rating of sleep-related PCS at T2 was significantly elevated compared to the pre-injury rating. Quade ANCOVAs indicated group differences in PCS subscales between patients and controls at T1, but not at T2. Patients and controls showed a similar performance in tests of attention at T1 and T2, but parental rating of participation at school was significantly reduced. Although cognitive PCS and attention were not correlated, there were significantly negative Spearman correlations between participation at home and pre-injury and concurrent PCS at T2. CONCLUSIONS: Our data imply that sleep-related PCS are still elevated weeks after injury and are thus a target for interventions after mTBI.

Processing speed and its association with working memory and episodic memory 3-6 months after pediatric mild traumatic brain injury.

OBJECTIVE: Following mild traumatic brain injury (mTBI), children show reduced processing speed (PS). Evidence suggests that slowed PS after TBI is associated with working memory deficits. Our aim was to investigate several forms of PS and to examine its impact on working and episodic memory performance in children after mTBI. METHOD: We included data of 64 children after mTBI and 57 healthy control children aged 8-16 years. PS (Color Naming, Coding, Symbol Search, Alertness) was compared between groups 1 week (T1) and 3-6 months (T2) after the injury; working and episodic memory outcome was compared between groups at T2. RESULTS: Alertness at T1 and Color Naming at T1 and T2 were significantly reduced following mTBI compared to controls, although most group differences in PS disappeared when patients with previous impairments and mTBI were excluded. PS was predictive for episodic and working memory performance 3-6 months after injury, whereas group was a significant predictor of working memory. CONCLUSIONS: Compared to healthy controls, children after mTBI showed reduced performance in verbal PS, which was associated with working memory. In children who are symptomatic after mTBI, diagnostic screening of PS could be helpful in identifying patients that could profit from speed-improving strategies.

The long-term negative impact of childhood stroke on language.

Objectives: This study aims to investigate the long-term language outcome in children with unilateral childhood stroke in comparison to those with perinatal strokes and typically developing individuals and to explore the impact of lesion-specific modifiers. Methods: We examined nine patients with childhood stroke, acquired between 0;2 and 16;1 years (CHILD; 3 female, median = 13.5 years, 6 left-sided), 23 patients with perinatal strokes (PERI; 11 female, median = 12.5 years, 16 left-sided), and 33 age-matched typically developing individuals (CONTROL; 15 female, median = 12.33 years). The language outcome was assessed using age-appropriate tasks of the Potsdam Illinois Test of Psycholinguistic Abilities (P-ITPA) or the Peabody Picture Vocabulary Test (PPVT). For group comparisons, study-specific language z-scores were calculated. Non-verbal intelligence was assessed using the Test of Non-verbal Intelligence (TONI-4), language lateralization with functional MRI, and lesion size with MRI-based volumetry. Results: All four patients with childhood stroke who initially presented with aphasic symptoms recovered from aphasia. Patients with childhood stroke showed significantly lower language scores than those in the control group, but their scores were similar to those of the patients with perinatal stroke, after adjusting for general intelligence (ANCOVA, language z-score CHILD = -0.30, PERI = -0.38, CONTROL = 0.42). Among the patients with childhood stroke, none of the possible modifying factors, including lesion side, correlated significantly with the language outcome. Conclusion: Childhood stroke, regardless of the affected hemisphere, can lead to chronic language deficits, even though affected children show a "full recovery." The rehabilitation of children and adolescents with childhood stroke should address language abilities, even after the usually quick resolution of clear aphasic symptoms.

Atypical language organization following perinatal infarctions of the left hemisphere is associated with structural changes in right-hemispheric grey matter.

AIM: To assess how atypical language organization after early left-hemispheric brain lesions affects grey matter in the contralesional hemisphere. METHOD: This was a cross-sectional study with between-group comparisons of 14 patients (six female, 8-26 years) with perinatal left-hemispheric brain lesions (two arterial ischemic strokes, 11 periventricular haemorrhagic infarctions, one without classification) and 14 typically developing age-matched controls (TDC) with functional magnetic resonance imaging (fMRI) documented left-hemispheric language organization (six female, 8-28 years). MRI data were analysed with SPM12, CAT12, and custom scripts. Language lateralization indices were determined by fMRI within a prefrontal mask and right-hemispheric grey matter group differences by voxel-based morphometry (VBM). RESULTS: FMRI revealed left-dominance in seven patients with typical language organization (TYP) and right-dominance in seven patients with atypical language organization (ATYP) of 14 patients. VBM analysis of all patients versus controls showed grey matter reductions in the middle temporal gyrus of patients. A comparison between the two patient subgroups revealed an increase of grey matter in the middle frontal gyrus in the ATYP group. Voxel-based regression analysis confirmed that grey matter increases in the middle frontal gyrus were correlated with atypical language organization. INTERPRETATION: Compatible with a non-specific lesion effect, we found areas of grey matter reduction in patients as compared to TDC. The grey matter increase in the middle frontal gyrus seems to reflect a specific compensatory effect in patients with atypical language organization. WHAT THIS PAPER ADDS: Perinatal stroke leads to decreased grey matter in the contralesional hemisphere. Atypical language organization is associated with grey matter increases in contralesional language areas.

Reduced structural connectivity in non-motor networks in children born preterm and the influence of early postnatal human cytomegalovirus infection.

Introduction: Preterm birth is increasingly recognized to cause lifelong functional deficits, which often show no correlate in conventional MRI. In addition, early postnatal infection with human cytomegalovirus (hCMV) is being discussed as a possible cause for further impairments. In the present work, we used fixel-based analysis of diffusion-weighted MRI to assess long-term white matter alterations associated with preterm birth and/or early postnatal hCMV infection. Materials and methods: 36 former preterms (PT, median age 14.8 years, median gestational age 28 weeks) and 18 healthy term-born controls (HC, median age 11.1 years) underwent high angular resolution DWI scans (1.5 T, b = 2 000 s/mm2, 60 directions) as well as clinical assessment. All subjects showed normal conventional MRI and normal motor function. Early postnatal hCMV infection status (CMV+ and CMV-) had been determined from repeated screening, ruling out congenital infections. Whole-brain analysis was performed, yielding fixel-wise metrics for fiber density (FD), fiber cross-section (FC), and fiber density and cross-section (FDC). Group differences were identified in a whole-brain analysis, followed by an analysis of tract-averaged metrics within a priori selected tracts associated with cognitive function. Both analyses were repeated while differentiating for postnatal hCMV infection status. Results: PT showed significant reductions of fixel metrics bilaterally in the cingulum, the genu corporis callosum and forceps minor, the capsula externa, and cerebellar and pontine structures. After including intracranial volume as a covariate, reductions remained significant in the cingulum. The tract-specific investigation revealed further reductions bilaterally in the superior longitudinal fasciculus and the uncinate fasciculus. When differentiating for hCMV infection status, no significant differences were found between CMV+ and CMV-. However, comparing CMV+ against HC, fixel metric reductions were of higher magnitude and of larger spatial extent than in CMV- against HC. Conclusion: Preterm birth can lead to long-lasting alterations of WM micro- and macrostructure, not visible on conventional MRI. Alterations are located predominantly in WM structures associated with cognitive function, likely underlying the cognitive deficits observed in our cohort. These observed structural alterations were more pronounced in preterms who suffered from early postnatal hCMV infection, in line with previous studies suggesting an additive effect.

Delayed episodic memory recall after one week is associated with executive functions and divided attention in pediatric epilepsy patients.

AIM: Recent studies suggest that although children with epilepsy may show normal learning and memory performance, accelerated long-term forgetting (ALF) may become evident over time. Our study examined associations between delayed episodic memory performance (recall 1-week after learning) and executive functions. METHOD: A consecutive sample of children with a diagnosis of idiopathic epilepsy with focal or generalized seizures, without morphologic or metabolic abnormalities (n = 20, mean age: 11.70 years) was compared to an IQ-matched healthy control group (n = 20, mean age: 11.55 years). We also assessed parents' and children's rating of forgetting in everyday life and explored its association with delayed episodic memory recall. RESULTS: Similar to results from recent studies of pediatric patients with temporal lobe epilepsy or genetic generalized epilepsy, our pediatric epilepsy patients showed a significantly elevated recall loss over time, although verbal learning, immediate and 30-minute recall was comparable to the matched control group. Additionally, delayed memory recall in patients was moderately associated with their subjective rating of forgetting, as well as with executive functions (verbal fluency and switching) and divided attention. INTERPRETATION: We assume that executive functions play a crucial role in deep memory encoding, facilitating stronger and more enduring memory traces. Given that approximately 20% of epilepsy patients - compared to a healthy reference sample - had a significantly reduced delayed recall and due to the clinical relevance of long-term memory, age-appropriate standard norms for free memory recall after 1-week are desirable.

Systematic Review of Accelerated Long-term Forgetting in Children and Adolescents With Neuropediatric Diseases.

Purpose of Review: Accelerated long-term forgetting (ALF) describes the phenomenon of normal learning and memory performance after short delays, but greater forgetting after longer delays, which is not objectified in standardized memory tests. The topic is attracting increasing interest due to its clinical importance. Studies investigating pediatric ALF remain rare, and no systematic review exists. Recent Findings: Based on our systematic literature search, 12 studies were found. Although most studies investigated ALF in children with epilepsy (n = 9), there is also evidence of ALF in children after traumatic brain injury (n = 1) and 22q11.2 deletion syndrome (n = 1). Summary: To date, only a dozen of studies have investigated pediatric ALF. There is evidence that ALF is not an epilepsy-specific disorder, replicating findings of studies with adult patients. Because ALF is missed using standardized assessments, we propose to add delayed time points of testing memory performance.

Enhancing the Follow-up Assessment of Very Preterm Children with Regard to 5-Year IQ Considering Socioeconomic Status.

BACKGROUND: Specifying peri- and postnatal factors in children born very preterm (VPT) that affect later outcome helps to improve long-term treatment. AIM: To enhance the predictability of 5-year cognitive outcome by perinatal, 2-year developmental and socio-economic data. SUBJECTS AND OUTCOME MEASURES: 92 VPT infants, born 2007-2009, gestational age<32 weeks and/or birthweight of 1500 g, were assessed longitudinally including basic neonatal, socio-economic (SES), 2-year Mental Developmental Index (MDI, Bayley Scales II), 5-year Mental Processing Composite (MPC, Kaufman-Assessment Battery for Children), and Language Screening for Preschoolers data. 5-year infants born VPT were compared to 34 term controls. RESULTS: The IQ of 5-year infants born VPT was 10 points lower than that of term controls and influenced independently by preterm birth and SES. MDI, SES, birth weight and birth complications explained 48% of the variance of the MPC. The MDI proved highly predictive (r=0.6, R2=36%) for MPC but tended to underestimate the cognitive outcome. A total of 61% of the 2-year infants born VPT were already correctly classified (specificity of .93, sensitivity of .54). CHAID decision tree technique identified SES as decisive for the outcome for infants born VPT with medium MDI results (76-91): They benefit from effects associated to a higher SES, while those with a poor MDI outcome and a birth weight≤890 g do not. CONCLUSION: Developmental follow-up of preterm children enhances the quality of prognosis and later outcome when differentially considering perinatal risks and SES.

Cognitive development after perinatal unilateral infarctions: No evidence for preferential sparing of verbal functions.

BACKGROUND: Even children with extensive perinatal left-sided lesions have been reported to show normal language functions based on right-hemispheric language reorganization. This reorganization can lead to deficits in originary right hemispheric functions ("crowding hypothesis"). In a previous study, however, we identified epilepsy (even when well-controlled), and not language reorganization, as the major risk factor for impaired nonverbal functions. Here, we asked whether verbal and nonverbal functions develop differently, and whether they share the same risk factors. METHODS: We investigated 23 patients (11f, Md = 12.56 years) with perinatal strokes (16 left-sided, 8 with epilepsy), and 23 healthy age-matched controls (8 f, Md = 12.42years). Language functions were assessed using the Potsdam Illinois Test of Psycholinguistic Abilities, nonverbal intelligence with the Test of Nonverbal Intelligence, language lateralization with functional MRI, and lesion size with MRI-based volumetry. RESULTS: We found no systematic difference between verbal and nonverbal skills in our patients or controls [median difference Z(PITPA)-Z(TONI): patients = -0.03, controls = -0.06]. Accordingly, verbal and nonverbal functions were strongly correlated in patients (r = 0.80) and in controls (r = 0.74). Language ability correlated significantly with epilepsy. Furthermore, in patients with epilepsies, verbal skills were significantly lower than in controls. CONCLUSION: In our cohort, we found no evidence for a differential effect of perinatal strokes on the development of verbal versus nonverbal functions, and, specifically, no evidence for a preferential sparing of verbal functions. Epilepsy, even when well-controlled, was confirmed as a single key risk factor for verbal functions.

Non-verbal Intelligence in Unilateral Perinatal Stroke Patients With and Without Epilepsies.

Background: The risk factors for impaired cognitive development after unilateral perinatal stroke are poorly understood. Non-verbal intelligence seems to be at particular risk, since language can shift to the right hemisphere and may thereby reduce the capacity of the right hemisphere for its originary functions. Pharmaco-refractory epilepsies, a frequent complication of perinatal strokes, often lead to impaired intelligence. Yet, the role of well-controlled epilepsies is less well-understood. Here, we investigated whether well-controlled epilepsies, motor impairment, lesion size, lesion side, and lateralization of language functions influence non-verbal functions. Methods: We recruited 8 patients with well-controlled epilepsies (9-26 years), 15 patients without epilepsies (8-23 years), and 23 healthy controls (8-27 years). All underwent the Test of Non-verbal Intelligence, a motor-independent test, which excludes biased results due to motor impairment. Language lateralization was determined with functional MRI, lesion size with MRI-based volumetry, and hand motor impairment with the Jebson-Taylor Hand Function-Test. Results: Patients with epilepsies showed significantly impaired non-verbal intelligence [Md = 89.5, interquartile range (IQR) = 13.5] compared with controls (Md = 103, IQR = 17). In contrast, patients without epilepsies (Md = 97, IQR = 15.0) performed within the range of typically developing children. A multiple regression analysis revealed only epilepsy as a significant risk factor for impaired non-verbal functions. Conclusion: In patients with unilateral perinatal strokes without epilepsies, the neuroplastic potential of one healthy hemisphere is able to support the development of normal non-verbal cognitive abilities, regardless of lesion size, lesion side, or language lateralization. In contrast, epilepsy substantially reduces this neuroplastic potential; even seizure-free patients exhibit below-average non-verbal cognitive functions.

Computerized Symbol Digit Modalities Test in a Swiss Pediatric Cohort - Part 2: Clinical Implementation.

BACKGROUND: Information processing speed (IPS) is a marker for cognitive function. It is associated with neural maturation and increases during development. Traditionally, IPS is measured using paper and pencil tasks requiring fine motor skills. Such skills are often impaired in patients with neurological conditions. Therefore, an alternative that does not need motor dexterity is desirable. One option is the computerized symbol digit modalities test (c-SDMT), which requires the patient to verbally associate numbers with symbols. METHODS: Eighty-six participants (8-16 years old; 45 male; 48 inpatients) were examined, 38 healthy and 48 hospitalized for a non-neurological disease. All participants performed the written SDMT, c-SDMT, and the Test of Non-verbal Intelligence Fourth Edition (TONI-4). Statistical analyses included a multivariate analysis of covariance (MANCOVA) for the effects of intelligence (IQ) and hospitalization on the performance of the SDMT and c-SDMT. A repeated measures analysis of variance (repeated measures ANOVA) was used to compare performance across c-SDMT trials between inpatients and outpatients. RESULTS: The MANCOVA showed that hospitalization had a significant effect on IPS when measured with the SDMT (p = 0.04) but not with the c-SDMT (p = 0.68), while IQ (p = 0.92) had no effect on IPS. Age (p < 0.001) was the best predictor of performance of both tests. The repeated measures ANOVA revealed no significant difference in within-test performance (p = 0.06) between outpatient and inpatient participants in the c-SDMT. CONCLUSION: Performance of the c-SDMT is not confounded by hospitalization and gives within-test information. As a valid and reliable measure of IPS for children and adolescents, it is suitable for use in both inpatient and outpatient populations.

Computerized Symbol Digit Modalities Test in a Swiss Pediatric Cohort Part 1: Validation.

OBJECTIVE: The objective of this study was to validate the computerized Symbol Digit Modalities Test (c-SDMT) in a Swiss pediatric cohort, in comparing the Swiss sample to the Canadian norms. Secondly, we evaluated sex effects, age-effects, and test-retest reliability of the c-SDMT in comparison to values obtained for the paper and pencil version of the Symbol Digit Modalities Test (SDMT). METHODS: This longitudinal observational study was conducted in a single-center setting at the University Children's Hospital of Bern. Our cohort consisted of 86 children (45 male and 41 female) aged from 8 to 16 years. The cohort included both healthy participants (n = 38) and patients (n = 48) hospitalized for a non-neurological disease. Forty eight participants were assessed during two testing sessions with the SDMT and the c-SDMT. RESULTS: Test-retest reliability was high in both tests (SDMT: ICC = 0.89, c-SDMT: ICC = 0.90). A reliable change index was calculated for the SDMT (RCIp = -3.18, 14.01) and the c-SDMT (RCIp = -5.45, 1.46) corrected for practice effects. While a significant age effect on information processing speed was observed, no such effect was found for sex. When data on the c-SDMT performance of the Swiss cohort was compared with that from a Canadian cohort, no significant difference was found for the mean time per trial in any age group. Norm values for age groups between 8 and 16 years in the Swiss cohort were established. CONCLUSION: Norms for the c-SDMT between the Swiss and the Canadian cohort were comparable. The c-SDMT is a valid alternative to the SDMT. It is a feasible and easy to administer bedside tool due to high reliability and the lack of motor demands.

Predicting Language Outcome After Left Hemispherotomy: A Systematic Literature Review.

OBJECTIVE: Hemidecortication is a therapeutic option in patients with drug-resistant structural epilepsy. If surgery is performed early enough in left-hemispheric pathology, the plasticity of the developing brain may enable the right hemisphere to take over language-if this has not occurred before surgery. A systematic overview of potential predictors of language outcome after left hemidecortication in children is warranted. METHODS: In a systematic literature review, we analyzed 58 studies on language lateralization after congenital or postneonatally acquired left-hemispheric pathology, and on language outcome after left-sided hemidisconnection, such as hemispherotomy. Single-subject data were pooled to determine the distribution of lateralization across etiologies in congenital lesions and across age groups in acute postneonatal lesions. A hierarchical linear regression assessed the influence of age at surgery, lesion type, age at seizure onset, and presurgery language function on language outcome after left hemidecortication. RESULTS: In acute postneonatal lesions, younger age at injury was significantly associated with right-sided language lateralization (Cramér V = 0.458; p = 0.039). In patients with hemidecortication, age at surgery was not significantly associated with language outcome (Cramér V = -0.056; p = 0.584). Presurgical language function was the most powerful predictor for postsurgical language outcome (F 4,47 = 7.35, p < 0.0001), with good presurgical language bearing the risk of postsurgical deterioration. In congenital pathology, right-sided language lateralization was most frequent in pre-/perinatal stroke (Cramér V = 0.357; p < 0.0001). CONCLUSIONS: We propose a presurgical decision algorithm with age, presurgical language function, language lateralization, and left-hemispheric structural pathology as decision points regarding surgery.

Cognitive and academic profiles in children with cerebral palsy: A narrative review.

BACKGROUND: Considerable effort has recently been made to improve the accurate diagnosis of cerebral palsy (CP) in childhood and to establish early intervention aiming to improve functional outcome. Besides the visible motor impairments, cognitive abilities are frequently affected but might remain unrecognised in children with mild forms. On the other hand, some severely disabled children with presumed intellectual disabilities might demonstrate normal-range reasoning capacities. Most studies on this topic have emphasized a variety of cognitive profiles (cognitive level) related to the type of cerebral palsy and the underlying brain lesions (biological level). However, little is known at the behavioural level, namely learning skills and educational achievement. OBJECTIVE: This narrative review aimed to discuss cognitive and scholastic skills typically affected in children with CP. METHODS: Online literature research for studies of cerebral palsy, cognition and academic achievement, extracting all relevant articles regardless of article type. RESULTS: In children with CP, intellectual disability is frequent and correlated with the degree of motor impairment and early epilepsy. Speech and language problems are prevalent in all forms of CP and might hamper everyday participation on varying levels depending on the degree of motor disability. Most children with CP have neuropsychological deficits affecting predominantly visuospatial functions, attention, and/or executive functions. These problems relate to academic performance and social participation. DISCUSSION: An adequate interdisciplinary follow-up of children with CP requires a sensitization of clinicians to the complex topic of cognitive and academic problems in this population and a better synergy between the medical and educational worlds.

Health-Related Quality of Life in Young Adults Following Pediatric Arterial Ischemic Stroke.

Background and Purpose- Pediatric arterial ischemic stroke (AIS) is a rare disease leading to long-lasting neurological sequelae. Little is known about the long-term health-related quality of life (HRQoL) of these patients. The study aims to compare HRQoL in young adults who have had pediatric AIS with a healthy control group. Methods- A cross-sectional study compared self-rated HRQoL, depression, fatigability, and behavior in pediatric stroke survivors to healthy controls. Patients with a confirmed diagnosis of pediatric AIS who were ≥18 years at the time of recruitment and ≥2 years after acute AIS, as well as healthy controls ≥18 years matched for age, sex, and socioeconomic status were included. Primary outcome was HRQoL measured with the Short Form Health Survey. Results- Thirty-three patients (median [interquartile range] aged 22 years [20-26]; 22 males, 67%) and 71 controls (median [interquartile range] aged 23 years [21-25]; 41 males, 58%) were included. Overall, HRQoL, depression, or fatigability did not differ between the patients and the control group. Patients rated themselves lower on the disinhibition scale (P=0.049) and tended to rate themselves lower on the executive dysfunction scale (P=0.076). Patients with a poor outcome 24 months after AIS showed a clear trend toward impairment of executive functioning (P=0.056) and work/productivity in the stroke-specific QoL (P=0.05). Conclusions- Self-rated HRQoL, depression, and fatigability in adult pediatric stroke survivors are comparable to healthy adult peers. A poor outcome 24 months after acute stroke might affect work performance and executive functioning in adulthood.

Attention Deficit Predicts Intellectual Functioning in Children with Neurofibromatosis Type 1.

AIMS: Attention deficit hyperactivity disorder (ADHD) is one of the most frequent neurocognitive impairments in neurofibromatosis type 1 (NF1) and a well-known risk factor for intellectual dysfunction in general. Since NF1 is per se associated with intellectual difficulties, this comorbidity may be crucial for the cognitive development of affected patients. In our study, we investigated if attention deficits are associated with intellectual functioning in NF1 and if children with NF1 plus ADHD differ in their intellectual and attention profiles from children affected by NF1-only or ADHD only. METHODS: 111 children aged between 6 and 12 years (53 NF1 plus ADHD, 28 NF1-only, 30 ADHD-only) performed the German version of the intelligence test WISC-IV and a continuous performance test (T.O.V.A.) to assess attention functions. Parents completed questionnaires about everyday attention and executive functions (Conners 3®, BRIEF). RESULTS: Children with NF1 plus ADHD showed significantly lower intelligence test scores (full-scale IQ: 89.39 [1.40]) than patients with NF1-only (full-scale IQ: 101.14 [1.98]; p < .001), and intellectual functioning correlated significantly with attention performance in NF1 (p < .001). As compared to NF1-only, attention, and executive functioning were impaired on several dimensions (T.O.V.A., Conners 3® and BRIEF) in NF1 plus ADHD. ADHD-only was associated with significantly higher problem scores regarding hyperactivity/impulsivity and inattention (Conners 3®). NF1-only was associated with inattentiveness when compared to the normative sample of the T.O.V.A. CONCLUSION: NF1 is associated with variable attention problems. Severe attention deficits appear to be a risk factor for intellectual dysfunction in NF1, more than NF1 without attention deficit. NF1 plus ADHD presents a specific cognitive profile, which differs from that of NF1 and from neurotypical ADHD.

Assessing motor, visual and language function using a single 5-minute fMRI paradigm: three birds with one stone.

Clinical functional Magnetic Resonance Imaging (fMRI) requires inferences on localization of major brain functions at the individual subject level. We hypothesized that a single "triple use" task would satisfy sensitivity and reliability requirements for successfully assessing the motor, visual and language domain in this context. This was tested here by the application in a group of healthy adults, assessing sensitivity and reliability at the individual subject level, separately for each domain.Our "triple use" task consisted of 2 conditions (condition 1, assessing motor and visual domain, and condition 2, assessing the language domain), serving mutually as active/control. We included 20 healthy adult subjects. Random effect analyses showed activation in primary motor, visual and language regions, as expected. Less expected regions were activated both for the motor and visual domains. Further, reliability of primary activation patterns was very high across individual subjects, with activation seen in 70-100% of subjects in primary motor, visual, and left-lateralized language regions.These findings suggest the "triple use" task to be reliable at the individual subject's level to assess motor, visual and language domains in the clinical fMRI context. Benefits of such an approach include shortening of acquisition time, simplicity of the task for each domain, and using a visual stimulus. Following establishment of reliability in adults, the task may also be a valuable addition in the pediatric clinical fMRI context, where each of these factors is of high relevance.

Motor dysfunction in NF1: Mediated by attention deficit or inherent to the disorder?

AIM: Attention deficit and compromised motor skills are both prevalent in Neurofibromatosis type 1 (NF1), but the relationship is unclear. We investigated motor function in children with NF1 and in children with Attention Deficit/Hyperactivity Disorder (ADHD), and explored if, in patients with NF1, attention deficit influences motor performance. METHODS: Motor performance was measured using the Movement Assessment Battery for Children (M-ABC) in 71 children (26 with NF1 plus ADHD, 14 with NF1 without ADHD, and 31 with ADHD without NF1) aged 6-12 years. RESULTS: There was a significant effect of group on motor performance. Both NF1 groups scored below children with ADHD without NF1. Attention performance mediated motor performance in children with ADHD without NF1, but not in children with NF1. CONCLUSIONS: Motor function is not mediated by attention performance in children with NF1. While in ADHD, attention deficit influences motor performance, motor problems in NF1 seem to be independent from attention deficit. This argues for different pathomechanisms in these two groups of developmental disorders.