Reliability of 3D freehand ultrasound to assess lower limb muscles in children with spastic cerebral palsy and typical development.

This study investigated the reliability of 3-dimensional freehand ultrasound (3DfUS) to quantify the size (muscle volume [MV] and anatomical cross-sectional area [aCSA]), length (muscle length [ML], tendon length [TL], and muscle tendon unit length [MTUL]), and echo-intensity (EI, whole muscle and 50% aCSA), of lower limb muscles in children with spastic cerebral palsy (SCP) and typical development (TD). In total, 13 children with SCP (median age 14.3 (7.3) years) and 13 TD children (median age 11.1 (1.7) years) participated. 3DfUS scans of rectus femoris, semitendinosus, medial gastrocnemius, and tibialis anterior were performed by two raters in two sessions. The intra- and inter-rater and intra- and inter-session reliability were defined with relative and absolute reliability measures, that is, intra-class correlation coefficients (ICCs) and absolute and relative standard error of measurement (SEM and SEM%), respectively. Over all conditions, ICCs for muscle size measures ranged from 0.818 to 0.999 with SEM%s of 12.6%-1.6%. For EI measures, ICCs varied from 0.233 to 0.967 with SEM%s of 15.6%-1.7%. Length measure ICCs ranged from 0.642 to 0.999 with SEM%s of 16.0%-0.5%. In general, reliability did not differ between the TD and SCP cohort but the influence of different muscles, raters, and sessions was not constant for all 3DfUS parameters. Muscle length and muscle tendon unit length were the most reliable length parameters in all conditions. MV and aCSA showed comparable SEM%s over all muscles, where tibialis anterior MV was most reliable. EI had low-relative reliability, but absolute reliability was better, with better reliability for the distal muscles in comparison to the proximal muscles. Combining these results with earlier studies describing muscle morphology assessed in children with SCP, 3DfUS seems sufficiently reliable to determine differences between cohorts and functional levels. The applicability on an individual level, for longitudinal follow-up and after interventions is dependent on the investigated muscle and parameter. Moreover, the semitendinosus, the acquisition, and processing of multiple sweeps, and the definition of EI and TL require further investigation. In general, it is recommended, especially for longitudinal follow-up studies, to keep the rater the same, while standardizing acquisition settings and positioning of the subject.

Teleintervention for users of augmentative and alternative communication devices: A systematic review.

AIM: To synthesize existing evidence on the effectiveness of speech-language teleinterventions delivered via videoconferencing to users of augmentative and alternative communication (AAC) devices. METHOD: A systematic literature search was conducted in 10 electronic databases, from inception until August 2021. Included were speech-language teleinterventions delivered by researchers and/or clinicians via videoconferencing to users of AAC devices, without restrictions on chronological age and clinical diagnosis. The quality of the studies included in the review was appraised using the Downs and Black checklist and the Single-Case Experimental Design Scale; risk of bias was assessed using the Risk Of Bias In Non-Randomized Studies - of Interventions and the single-case design risk of bias tools. RESULTS: Six teleinterventions including 25 participants with a variety of conditions, such as Down syndrome, autism, Rett syndrome, and amyotrophic lateral sclerosis met the inclusion criteria. Five studies used a single-case experimental design and one was a cohort study. Teleinterventions included active consultation (n = 2), functional communication training (n = 2), brain-computer interface (n = 1), and both teleintervention and in-person intervention (n = 1). All teleinterventions reported an increase in participants' independent use of AAC devices during the training sessions compared to baseline, as well as an overall high satisfaction and treatment acceptability. INTERPRETATION: Speech-language teleinterventions for users of AAC devices show great potential for a successful method of service delivery. Future telehealth studies with larger sample sizes and more robust methodology are strongly encouraged to allow the generalization of results across different populations. WHAT THIS PAPER ADDS: Individuals can learn to use augmentative and alternative communication (AAC) devices independently during tele-AAC interventions. Service providers and recipients reported an overall high satisfaction and acceptability for AAC services delivered via teleinterventions. Speech-language teleinterventions may be an effective method of providing AAC intervention services.

Eye movements and stress during eye-tracking gaming performance in children with dyskinetic cerebral palsy.

AIM: This study aimed to explore eye movements and stress during eye-tracking gaming performance in children with dyskinetic cerebral palsy (CP) compared with typically developing children, and associations between eye-tracking performance, eye movements, stress, and participants' characteristics. METHOD: This cohort study included 12 children with dyskinetic CP aged 5 to 12 years (mean age 8 years 7 months, standard deviation [SD] 2 years 3 months) and 23 typically developing children aged 5 to 13 years (mean age 9 years 0 months, SD 2 years 7 months). Participants played 10 eye-tracking games. Tobii X3-120 and Tobii Pro Lab were used to record and analyse eye movements. Stress was assessed through heart rate variability (HRV), recorded during rest, and eye-tracking performance using the Bittium Faros360° ECG Holter device. Eye-tracking performance was measured using gaming completion time. Fixation and saccade variables were used to quantify eye movements, and time- and frequency-domain variables to quantify HRV. Non-parametric statistics were used. RESULTS: Gaming completion time was significantly different (p < 0.001) between groups, and it was negatively correlated with experience (rs  = -0.63, p = 0.029). No significant differences were found between groups in fixation and saccade variables. HRV significantly changed from rest to eye-tracking performance only in typically developing children and not in children with dyskinetic CP. INTERPRETATION: Children with dyskinetic CP took longer to perform the 10 games, especially the inexperienced users, indicating the importance of the early provision of eye-tracking training opportunities. It seems that eye-tracking tasks are not a source of increased stress and effort in children with dyskinetic CP. WHAT THIS PAPER ADDS: Participants with dyskinetic cerebral palsy (CP) took twice as long to perform 10 eye-tracking games than typically developing peers. Participants with dyskinetic CP with previous eye-tracking experience performed the games faster. Fixation and saccade variables were not significantly different between children with and without dyskinetic CP. Heart rate variability showed no differences between rest and performance in participants with dyskinetic CP. Gross Motor Function Classification System, Manual Ability Classification System, and Viking Speech Scale levels were not correlated to the eye movements or stress variables.

Caudate and cerebellar involvement in altered P2 and P3 components of GO/NoGO evoked potentials in children with attention-deficit/hyperactivity disorder.

Previous studies showed reduced activity of the anterior cingulate cortex (ACC) and supplementary motor area during inhibition in children with attention-deficit/hyperactivity disorder (ADHD). This study aimed to investigate deep brain generators underlying alterations of evoked potential components triggered by visual GO/NoGO tasks in children with ADHD compared with typically developing children (TDC). Standardized weighted low-resolution electromagnetic tomography (swLORETA) source analysis showed that lower GO-P3 component in children with ADHD was explained not only by a reduced contribution of the frontal areas but also by a stronger contribution of the anterior part of the caudate nucleus in these children compared with TDC. While the reduction of the NoGO-P3 component in children with ADHD was essentially explained by a reduced contribution of the dorsal ACC, the higher NoGO-P2 amplitude in these children was concomitant to the reduced contribution of the dorsolateral prefrontal cortex, the insula, and the cerebellum. These data corroborate previous findings showed by fMRI studies and offered insight relative to the precise time-related contribution of the caudate nucleus and the cerebellum during the automatic feature of inhibition processes in children with ADHD. These results were discussed regarding the involvement of the fronto-basal ganglia and fronto-cerebellum networks in inhibition and attention alterations in ADHD.

Test-retest reliability of the Dyskinesia Impairment Scale: measuring dystonia and choreoathetosis in dyskinetic cerebral palsy.

AIM: To assess test-retest reliability of the Dyskinesia Impairment Scale (DIS) in children and young adults with dyskinetic cerebral palsy (CP). METHOD: Dystonia and choreoathetosis were assessed in 15 participants with dyskinetic CP (13 males, 2 females; age range 5-22y, mean 14y, SD 4y) using the DIS in two separate sessions over 7 days. Exclusion criteria were changes in muscle relaxant medication within the previous 3 months, orthopaedic or neurosurgical interventions within the previous year, and spinal fusion. Intraclass correlation coefficient, confidence intervals (CI), standard error of measurement, and the minimal detectable difference (MDD) were determined for test-retest reliability. RESULT: Intraclass correlation coefficients of the DIS, the dystonia subscale of the DIS, and the choreoathetosis subscale of the DIS were 0.98 (95% CI 0.94-0.99), 0.97 (95% CI 0.92-0.99), and 0.96 (95% CI 0.90-0.99). The standard error of measurement and MDD were 2.6% and 7.2%. INTERPRETATION: The DIS is a reliable tool to assess dystonia and choreoathetosis; it remains stable over time in children and young adults with dyskinetic CP. These results add to the current evidence for good clinimetric properties of the DIS. WHAT THIS PAPER ADDS: The Dyskinesia Impairment Scale (DIS) shows stability in scoring dystonia and choreoathetosis. The total DIS score and dystonia and choreoathetosis subscales are clinically useful.

Duplication 2p16 is associated with perisylvian polymicrogyria.

Polymicrogyria (PMG) is a heterogeneous brain malformation that may result from prenatal vascular disruption or infection, or from numerous genetic causes that still remain difficult to identify. We identified three unrelated patients with polymicrogyria and duplications of chromosome 2p, defined the smallest region of overlap, and performed gene pathway analysis using Cytoscape. The smallest region of overlap in all three children involved 2p16.1-p16.3. All three children have bilateral perisylvian polymicrogyria (BPP), intrauterine and postnatal growth deficiency, similar dysmorphic features, and poor feeding. Two of the three children had documented intellectual disability. Gene pathway analysis suggested a number of developmentally relevant genes and gene clusters that were over-represented in the critical region. We narrowed a rare locus for polymicrogyria to a region of 2p16.1-p16.3 that contains 33-34 genes, 23 of which are expressed in cerebral cortex during human fetal development. Using pathway analysis, we showed that several of the duplicated genes contribute to neurodevelopmental pathways including morphogen, cytokine, hormonal and growth factor signaling, regulation of cell cycle progression, cell morphogenesis, axonal guidance, and neuronal migration. These findings strengthen the evidence for a novel locus associated with polymicrogyria on 2p16.1-p16.3, and comprise the first step in defining the underlying genetic etiology.

Somatic mutations in cerebral cortical malformations.

BACKGROUND: Although there is increasing recognition of the role of somatic mutations in genetic disorders, the prevalence of somatic mutations in neurodevelopmental disease and the optimal techniques to detect somatic mosaicism have not been systematically evaluated. METHODS: Using a customized panel of known and candidate genes associated with brain malformations, we applied targeted high-coverage sequencing (depth, ≥200×) to leukocyte-derived DNA samples from 158 persons with brain malformations, including the double-cortex syndrome (subcortical band heterotopia, 30 persons), polymicrogyria with megalencephaly (20), periventricular nodular heterotopia (61), and pachygyria (47). We validated candidate mutations with the use of Sanger sequencing and, for variants present at unequal read depths, subcloning followed by colony sequencing. RESULTS: Validated, causal mutations were found in 27 persons (17%; range, 10 to 30% for each phenotype). Mutations were somatic in 8 of the 27 (30%), predominantly in persons with the double-cortex syndrome (in whom we found mutations in DCX and LIS1), persons with periventricular nodular heterotopia (FLNA), and persons with pachygyria (TUBB2B). Of the somatic mutations we detected, 5 (63%) were undetectable with the use of traditional Sanger sequencing but were validated through subcloning and subsequent sequencing of the subcloned DNA. We found potentially causal mutations in the candidate genes DYNC1H1, KIF5C, and other kinesin genes in persons with pachygyria. CONCLUSIONS: Targeted sequencing was found to be useful for detecting somatic mutations in patients with brain malformations. High-coverage sequencing panels provide an important complement to whole-exome and whole-genome sequencing in the evaluation of somatic mutations in neuropsychiatric disease. (Funded by the National Institute of Neurological Disorders and Stroke and others.).