Background: Ayres Sensory Integration (ASI) is widely employed by occupational therapists working with clients who experience challenges in sensory integration, including those with autism spectrum ...disorder (ASD). However, there is a dearth of research examining the feasibility of ASI outside of Western nations. This study documented the barriers associated with ASI in Saudi Arabia and assessed whether the intervention could improve process and participation skills.
Methods: Single-Subject experimental design was used. The participant was a 4-year-old girl with ASD from Saudi Arabia. Data were gathered on sensory processing, motor skills, and participation in activities of daily living. The study used semi-structured interviews and assessments (Sensory Integration and Praxis Tests, the Sensory Processing Measure-Preschool, and the Peabody Developmental Motor Scale-2) to develop goals, identify outcome measures, and plan an ASI intervention.
Results: Despite the limited availability of resources (e.g., toys, treatment spaces) and Arabic measures, improvements were observed on motor and sensory tasks and in occupational performance.
Conclusion: ASI that adheres to the ASI fidelity tool can be of value for Saudi Arabian children with ASD. Additionally, the study provides a stepping-stone to further research for occupational therapists in Saudi Arabia working with children with ASD.
Little information is available about autism spectrum disorder services in the Kingdom of Saudi Arabia. A sample of 205 parents completed an online survey about the use of autism spectrum disorder ...services for their children. The results revealed that on average, children began services by 3.3 years. Most parents reported utilizing non-medical treatments followed by biomedical treatments and cultural and religious treatment. The age at the initiation of services and the type of treatments used differed by parent’s income, educational attainment, the extent of knowledge about autism spectrum disorders, and geographic location. Some child characteristics also influenced the use of services. The disparities in service utilization in Saudi Arabia point to the need to develop policy and interventions that can mitigate the paucity of services for children with autism spectrum disorders. More research is needed to better understand service use and the decision-making processes that underlie treatment selection by parents of children with autism spectrum disorders in the Kingdom of Saudi Arabia.
Objective
Through international collaboration, we evaluated the phenotypic aspects of a multiethnic cohort of KCNT1‐related epilepsy and explored genotype‐phenotype correlations associated with ...frequently encountered variants.
Methods
A cross‐sectional analysis of children harboring pathogenic or likely pathogenic KCNT1 variants was completed. Children with one of the two more common recurrent KCNT1 variants were compared with the rest of the cohort for the presence of particular characteristics.
Results
Twenty‐seven children (15 males, mean age = 40.8 months) were included. Seizure onset ranged from 1 day to 6 months, and half (48.1%) exhibited developmental plateauing upon onset. Two‐thirds had epilepsy of infancy with migrating focal seizures (EIMFS), and focal tonic seizures were common (48.1%). The most frequent recurrent KCNT1 variants were c.2800G>A; p.Ala934Thr (n = 5) and c.862G>A; p.Gly288Ser (n = 4). De novo variants were found in 96% of tested parents (23/24). Sixty percent had abnormal magnetic resonance imaging (MRI) findings. Delayed myelination, thin corpus callosum, and brain atrophy were the most common. One child had gray‐white matter interface indistinctness, suggesting a malformation of cortical development. Several antiepileptic drugs (mean = 7.4/patient) were tried, with no consistent response to any one agent. Eleven tried quinidine; 45% had marked (>50% seizure reduction) or some improvement (25%‐50% seizure reduction). Seven used cannabidiol; 71% experienced marked or some improvement. Fourteen tried diet therapies; 57% had marked or some improvement. When comparing the recurrent variants to the rest of the cohort with respect to developmental trajectory, presence of EIMFS, >500 seizures/mo, abnormal MRI, and treatment response, there were no statistically significant differences. Four patients died (15%), none of sudden unexpected death in epilepsy.
Significance
Our cohort reinforces common aspects of this highly pleiotropic entity. EIMFS manifesting with refractory tonic seizures was the most common. Cannabidiol, diet therapy, and quinidine seem to offer the best chances of seizure reduction, although evidence‐based practice is still unavailable.
Research examining the age of diagnosis of autism spectrum disorder (ASD) and its influencing factors mostly originate from developed Western countries, providing little to no systematic information ...about the understanding and management of ASD in the rest of the world. The present exploratory study examined the influence of child and family characteristics on the age of ASD diagnosis in Saudi Arabia.
The median age at diagnosis was 3.0 years and was associated with some child and family characteristics. A 1 year increase in child's age was associated with a 0.1 year increase in age of diagnosis (95% CI 0.05, 0.12). Children who did not respond to their name were diagnosed 0.3 years earlier than other children (95% CI - 0.60, - 0.05), and engaging in challenging behavior was associated with a 0.5 year increase in age of diagnosis (95% CI 0.20, 0.81). A lack of comorbidity was associated with a 0.6 year increase in the age of diagnosis compared to the diagnosis age of children with comorbidity (95% CI 0.13, 1.01). Finally, those residing outside of Saudi Arabia were diagnosed with ASD 0.9 years earlier than those residing in Saudi Arabia (95% CI - 0.171, - 0.11).
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with genetic and clinical heterogeneity. The interplay of de novo and inherited rare variants has been suspected in the ...development of ASD. Here, we applied whole exome sequencing (WES) on 19 trios from singleton Saudi families with ASD. We developed an analysis pipeline that allows capturing both de novo and inherited rare variants predicted to be deleterious. A total of 47 unique rare variants were detected in 17 trios including 38 which are newly discovered. The majority were either autosomal recessive or X-linked. Our pipeline uncovered variants in 15 ASD-candidate genes, including 5 (GLT8D1, HTATSF1, OR6C65, ITIH6 and DDX26B) that have not been reported in any human condition. The remaining variants occurred in genes formerly associated with ASD or other neurological disorders. Examples include SUMF1, KDM5B and MXRA5 (Known-ASD genes), PRODH2 and KCTD21 (implicated in schizophrenia), as well as USP9X and SMS (implicated in intellectual disability). Consistent with expectation and previous studies, most of the genes implicated herein are enriched for biological processes pertaining to neuronal function. Our findings underscore the private and heterogeneous nature of the genetic architecture of ASD even in a population with high consanguinity rates.
This prospective study assessed the exposure to phthalates of preterm neonates who received total parenteral nutrition (TPN) during their stay in the neonatal intensive care unit (NICU) and the risk ...of neurodevelopment delays at the age of 2 months. Our study recruited 33 preterm neonates who required TPN upon NICU admission. Urine samples for analyzing phthalate metabolites were obtained at admission and then daily until the last day of receiving TPN. Phthalates in the daily TPN received by the preterm neonates were analyzed. The neurodevelopment of the neonates was assessed using the Ages and Stages Questionnaire Edition 3 (ASQ-3). Diethyl phthalate and butyl benzyl phthalate were found in all TPN samples, while 27% and 83% contained dibutyl phthalate and di-(2-ethylhexyl) phthalate (DEHP), respectively. Yet, the daily dose of each phthalate that our preterm neonates received from TPN was much lower than the recommended tolerable limit. Urinary levels of monobenzyl phthalate and four metabolites of DEHP i.e., mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) and the sum of four DEHP metabolites (∑
DEHP) increased significantly in preterm neonates before discharge. However, these levels were not correlated with their phthalate parent compounds in TPN, suggesting other sources of exposure in the NICU. At 2 months, we found that urinary levels of mono-iso-butyl phthalate (MiBP), MECPP, MEHP, and ∑
DEHP were inversely related to fine motor skills. After adjusting for head circumference, the inverse relationships remained significant, suggesting direct effects from phthalates. Given the extreme vulnerability of our population, it is critical to minimize exposure to phthalates during their NICU stay.
Developmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive ...mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteoglycans and glycolipids. Consistent with being loss-of-function alleles, we show using patients' primary fibroblasts and biochemical assays, that these mutations either impair UGDH stability, oligomerization, or enzymatic activity. In vitro, patient-derived cerebral organoids are smaller with a reduced number of proliferating neuronal progenitors while mutant ugdh zebrafish do not phenocopy the human disease. Our study defines UGDH as a key player for the production of extracellular matrix components that are essential for human brain development. Based on the incidence of variants observed, UGDH mutations are likely to be a frequent cause of recessive epileptic encephalopathy.
Proteins anchored to the cell surface via glycosylphosphatidylinositol (GPI) play various key roles in the human body, particularly in development and neurogenesis. As such, many developmental ...disorders are caused by mutations in genes involved in the GPI biosynthesis and remodeling pathway. We describe ten unrelated families with bi-allelic mutations in PIGB, a gene that encodes phosphatidylinositol glycan class B, which transfers the third mannose to the GPI. Ten different PIGB variants were found in these individuals. Flow cytometric analysis of blood cells and fibroblasts from the affected individuals showed decreased cell surface presence of GPI-anchored proteins. Most of the affected individuals have global developmental and/or intellectual delay, all had seizures, two had polymicrogyria, and four had a peripheral neuropathy. Eight children passed away before four years old. Two of them had a clinical diagnosis of DOORS syndrome (deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures), a condition that includes sensorineural deafness, shortened terminal phalanges with small finger and toenails, intellectual disability, and seizures; this condition overlaps with the severe phenotypes associated with inherited GPI deficiency. Most individuals tested showed elevated alkaline phosphatase, which is a characteristic of the inherited GPI deficiency but not DOORS syndrome. It is notable that two severely affected individuals showed 2-oxoglutaric aciduria, which can be seen in DOORS syndrome, suggesting that severe cases of inherited GPI deficiency and DOORS syndrome might share some molecular pathway disruptions.
Background: Ayres Sensory Integration (ASI) is widely employed by occupational therapists working with clients who experience challenges in sensory integration, including those with autism spectrum ...disorder (ASD). However, there is a dearth of research examining the feasibility of ASI outside of Western nations. This study documented the barriers associated with ASI in Saudi Arabia and assessed whether the intervention could improve process and participation skills.
Methods: A pre-test/post-test case study design was used. The participant was a 4-year-old girl with ASD from Saudi Arabia. Data were gathered on sensory processing, motor skills, and participation in activities of daily living. The study used semi-structured interviews and assessments (Sensory Integration and Praxis Tests, the Sensory Processing Measure-Preschool, and the Peabody Developmental Motor Scale-2) to develop goals, identify outcome measures, and plan an ASI intervention.
Results: Despite the limited availability of resources (e.g., toys, treatment spaces) and Arabic measures, improvements were observed on motor and sensory tasks and in occupational performance.
Conclusion: ASI that adheres to the ASI fidelity tool can be of value for Saudi Arabian children with ASD. Additionally, the study provides a stepping-stone to further research for occupational therapists in Saudi Arabia working with children with ASD.
Filtering of unwanted signals has a great impact on the performance of EEG signal processing applied to neurological disorders diagnosis. It is so difficult to remove undesirable noises using static ...filtering approaches as the performance of such techniques is strongly relying on specific EEG signal sub-bands, whose locations differ from one subject to another. In this paper, we present a novel dynamic filtering approach, which makes use of Finite and Infinite Impulse Response (FIR and IIR) filters along with a Recurrent Neural Networks using a Gated-Recurrent Unit (RNN-GRU), to identify and preprocess the most informative sub-bands pertaining to a particular neurological disorder. This combination of RNN with GRU requires more hidden layers than for conventional NN structures, and therefore offers much higher capacity to learn fitting and extract features from highly complex EEG data recording to afford better harmonization of the diagnosis process. Followed by an Independent Component Analysis (ICA) algorithm, all extracted features become independent to facilitate classification of clinical disorders using Convolutional Neural Network (CNN). The proposed diagnosis system achieves an average of 100% classification accuracy for epilepsy according to an offline diagnosis process using Bonn and MIT datasets, and when the same system is applied to autism provides an average accuracy of 99.5% using KAU dataset. The presented dynamic deep-learning approach applied to EEG classification pipeline, which includes artifact removal, feature extraction and classification, leads to significant improvements in the accuracy of the diagnosis classification regarding the targeted neurological pathologies.
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