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Journal of Child Neurology Mar 2024Aicardi-Goutières syndrome is a genetic inflammatory disorder resulting in dispersed neurologic dysfunction. Despite a recognition of overall motor impairment, fine and...
Aicardi-Goutières syndrome is a genetic inflammatory disorder resulting in dispersed neurologic dysfunction. Despite a recognition of overall motor impairment, fine and visual motor skills are undercharacterized. We hypothesize that there is a spectrum of fine and visual motor skills in the Aicardi-Goutières syndrome population as captured by a standard outcome measure, the Peabody Developmental Motor Scales (PDMS-2), which will be proportional to overall disease severity.In a cohort of 74 subjects, the Peabody Developmental Motor Scales-2 grasping and visual-motor integration subtests were administered concurrently with the Aicardi-Goutières syndrome Severity Scale (severe [range 0-3], moderate [range 4-8], and attenuated [range 9-11]). The cohort was also compared by genotype and performance as defined by raw scores. The distribution of Peabody Developmental Motor Scales-2 scores within a genotype was assessed by interquartile ranges (IQRs).Peabody Developmental Motor Scales-2 grasping and visual-motor integration performance was the least variable in the -cohort (IQR: 10.00-12.00) versus the and cohorts (IQR: 51.00-132.00 and 48.50-134.00, respectively). Neurologic severity highly correlated with both fine and visual motor skills (Spearman correlation: = 0.87, 0.91, respectively). A floor effect (lowest 10% of possible scores) was observed within the severe cohort (n = 32/35), whereas a ceiling effect (top 10%) was observed in the attenuated cohort (n = 13/17).This study characterized the spectrum of fine and visual motor function in the Aicardi-Goutières syndrome population, which correlated with overall neurologic dysfunction. The Peabody Developmental Motor Scales-2 grasping and visual-motor integration showed promise as potential assessment tools in moderate and attenuated Aicardi-Goutières syndrome cohorts. A better understanding of fine and visual motor function in this population will benefit clinical care and clinical trial design.
Topics: Humans; Female; Nervous System Malformations; Male; Child; Autoimmune Diseases of the Nervous System; Motor Skills; Child, Preschool; Cohort Studies; Severity of Illness Index; Adolescent; Infant; Psychomotor Performance
PubMed: 38532733
DOI: 10.1177/08830738241241786 -
Brain : a Journal of Neurology Mar 2024Inherited glycosylphosphatidylinositol deficiency disorders (IGDs) are a group of rare multisystem disorders arising from pathogenic variants in...
Inherited glycosylphosphatidylinositol deficiency disorders (IGDs) are a group of rare multisystem disorders arising from pathogenic variants in glycosylphosphatidylinositol anchor pathway (GPI-AP) genes. Despite associating 24 of at least 31 GPI-AP genes with human neurogenetic disease, prior reports are limited to single genes without consideration of the GPI-AP as a whole and with limited natural history data. In this multinational retrospective observational study, we systematically analyse the molecular spectrum, phenotypic characteristics, and natural history of 83 individuals from 75 unique families with IGDs, including 70 newly reported individuals: the largest single cohort to date. Core clinical features were developmental delay or intellectual disability (DD/ID, 90%), seizures (83%), hypotonia (72%), and motor symptoms (64%). Prognostic and biologically significant neuroimaging features included cerebral atrophy (75%), cerebellar atrophy (60%), callosal anomalies (57%), and symmetric restricted diffusion of the central tegmental tracts (60%). Sixty-one individuals had multisystem involvement including gastrointestinal (66%), cardiac (19%), and renal (14%) anomalies. Though dysmorphic features were appreciated in 82%, no single dysmorphic feature had a prevalence >30%, indicating substantial phenotypic heterogeneity. Follow-up data were available for all individuals, 15 of whom were deceased at the time of writing. Median age at seizure onset was 6 months. Individuals with variants in synthesis stage genes of the GPI-AP exhibited a significantly shorter time to seizure onset than individuals with variants in transamidase and remodelling stage genes of the GPI-AP (P=0.046). Forty individuals had intractable epilepsy. The majority of individuals experienced delayed or absent speech (95%); motor delay with non-ambulance (64%); and severe-to-profound DD/ID (59%). Individuals with a developmental epileptic encephalopathy (51%) were at greater risk of intractable epilepsy (P=0.003), non-ambulance (P=0.035), ongoing enteral feeds (P<0.001), and cortical visual impairment (P=0.007). Serial neuroimaging showed progressive cerebral volume loss in 87.5% and progressive cerebellar atrophy in 70.8%, indicating a neurodegenerative process. Genetic analyses identified 93 unique variants (106 total), including 22 novel variants. Exploratory analyses of genotype-phenotype correlations using unsupervised hierarchical clustering identified novel genotypic predictors of clinical phenotype and long-term outcome with meaningful implications for management. In summary, we expand both the mild and severe phenotypic extremities of the IGDs; provide insights into their neurological basis; and, vitally, enable meaningful genetic counselling for affected individuals and their families.
PubMed: 38456468
DOI: 10.1093/brain/awae056 -
Cold Spring Harbor Molecular Case... Jun 2023PPP2 syndrome type R5D, or Jordan's syndrome, is a neurodevelopmental disorder caused by pathogenic missense variants in , a β-subunit of the Protein Phosphatase 2A...
PPP2 syndrome type R5D, or Jordan's syndrome, is a neurodevelopmental disorder caused by pathogenic missense variants in , a β-subunit of the Protein Phosphatase 2A (PP2A). The condition is characterized by global developmental delays, seizures, macrocephaly, ophthalmological abnormalities, hypotonia, attention disorder, social and sensory challenges often associated with autism, disordered sleep, and feeding difficulties. Among affected individuals, there is a broad spectrum of severity, and each person only has a subset of all associated symptoms. Some, but not all, of the clinical variability is due to differences in the genotype. These suggested clinical care guidelines for the evaluation and treatment of individuals with PPP2 syndrome type R5D are based on data from 100 individuals reported in the literature and from an ongoing natural history study. As more data are available, particularly for adults and regarding treatment response, we anticipate that revisions to these guidelines will be made.
Topics: Adult; Humans; Intellectual Disability; Jordan; Neurodevelopmental Disorders; Autistic Disorder; Syndrome; Reference Standards; Protein Phosphatase 2
PubMed: 37339871
DOI: 10.1101/mcs.a006285 -
BMC Pediatrics Dec 2023Child psychomotor development and factors affecting it today is the subject of interest of many studies, in particular by the experts involved in the protection and...
BACKGROUND
Child psychomotor development and factors affecting it today is the subject of interest of many studies, in particular by the experts involved in the protection and improvement of children's health. There is limited evidence on developmental delay among under-five children in low-income countries like Ethiopia. The aim of this study was to assess gross motor developmental delay and associated factors among under-five children attending public health facilities of Dessie city, Ethiopia.
METHODS
Facility based cross sectional study design was used among under-five children attending under-five OPD in public health facilities of Dessie town from July 1, 2020 to August 15, 2021. A total of, 417 under-five children were systematically selected based on their average number of clients in a month. A pretested structured questionnaire was used for data collection, and data was entered into Epi-data 3.1 version and it was exported to STATA version 14 for analysis. Binary logistic regression analysis was used to identify factors associated with the outcome variable. Odds ratio with 95% confidence interval was used to show the strength and direction of association respectively and P-value less than 0.05 is used to declare statistical significance.
RESULTS
The overall proportion of gross motor developmental delay among under-five children attending health facilities of Dessie city, Ethiopia was 16.31%, 95% CI: (13.05, 20.19). Increased age of the child [AOR = 0.97, 95% CI: (0.96, 0.99)], increased gestational age during pregnancy [AOR = 0.47, 95% CI: (0.37, 0.65)], being male [AOR = 5.26, 95% CI: (1.76, 15.67)], having history of alcohol intake during pregnancy [AOR = 7.40, 95% CI: (2.36, 23.25)], taking iron during pregnancy [AOR = 0.04, 95% CI: (0.01, 0.15)], facing fetal and/or maternal complication [AOR = 4.98, 95% CI: (1.20, 20.62)], having instrumental delivery [AOR = 9.78, 95% CI: (2.48, 38.60)] were significantly associated with gross motor developmental delay.
CONCLUSIONS
The gross motor developmental delay among under-five children was higher as compared to other literatures. This study indicated that, age and sex of the child, iron and alcohol intake during pregnancy, gestational age, mode of delivery and any complication to her and or her neonate were independent variables which showed statistical significant association. The physicians should advise mothers to take iron-folic acid supplement properly and to avoid intake of alcohol during pregnancy. In addition, they should focus on those mothers who faced any complication to her and/or her neonate and better to discourage instrumental delivery unless there are no other options.
Topics: Infant, Newborn; Female; Pregnancy; Child; Humans; Male; Ethiopia; Cross-Sectional Studies; Mothers; Health Facilities; Iron
PubMed: 38110857
DOI: 10.1186/s12887-023-04461-9 -
Frontiers in Neurorobotics 2023Robot learning based on implicitly extracted error detections (e.g., EEG-based error detections) has been well-investigated in human-robot interaction (HRI). In...
Robot learning based on implicitly extracted error detections (e.g., EEG-based error detections) has been well-investigated in human-robot interaction (HRI). In particular, the use of error-related potential (ErrP) evoked when recognizing errors is advantageous for robot learning when evaluation criteria cannot be explicitly defined, e.g., due to the complex behavior of robots. In most studies, erroneous behavior of robots were recognized visually. In some studies, visuo-tactile stimuli were used to evoke ErrPs or a tactile cue was used to indicate upcoming errors. To our knowledge, there are no studies in which ErrPs are evoked when recognizing errors only via the tactile channel. Hence, we investigated ErrPs evoked by tactile recognition of errors during HRI. In our scenario, subjects recognized errors caused by incorrect behavior of an orthosis during the execution of arm movements tactilely. EEG data from eight subjects was recorded. Subjects were asked to give a motor response to ensure error detection. Latency between the occurrence of errors and the response to errors was expected to be short. We assumed that the motor related brain activity is timely correlated with the ErrP and might be used from the classifier. To better interpret and test our results, we therefore tested ErrP detections in two additional scenarios, i.e., without motor response and with delayed motor response. In addition, we transferred three scenarios (motor response, no motor response, delayed motor response). Response times to error was short. However, high ErrP-classification performance was found for all subjects in case of motor response and no motor response condition. Further, ErrP classification performance was reduced for the transfer between motor response and delayed motor response, but not for the transfer between motor response and no motor response. We have shown that tactilely induced errors can be detected with high accuracy from brain activity. Our preliminary results suggest that also in tactile ErrPs the brain response is clear enough such that motor response is not relevant for classification. However, in future work, we will more systematically investigate tactile-based ErrP classification.
PubMed: 38162893
DOI: 10.3389/fnbot.2023.1297990 -
Advances in Rehabilitation Science and... 2023Motor skills and movement-related functioning significantly shape how children experience and interact with the world around them. Among infants and young children,... (Review)
Review
Motor skills and movement-related functioning significantly shape how children experience and interact with the world around them. Among infants and young children, developmental motor disorders contribute to delays with motor, cognitive, and psychosocial development. Early and accurate identification of these disorders is necessary to facilitate timely access to therapeutic interventions that minimize the long-term effects of disability on everyday activities and participation. In the United States, motor assessments commonly used among children 0 to 3 years focus on completion of specific motor skills at a single point in time, which provides only a part of the greater picture that is a child's motor and movement-related functioning. Video-capture methods, like the General Movements Assessment (GMA) and the Infant Motor Profile (IMP), offer greater accuracy and predictive power to (1) identify motor deficits in young children and (2) facilitate early access to supportive, therapeutic intervention.
PubMed: 37928362
DOI: 10.1177/27536351231207740 -
Frontiers in Bioscience (Landmark... Dec 2023Amyotrophic lateral sclerosis (ALS) is a systemic disease with multiple pathological effects, including neuroinflammation, oxidative stress, autophagy, mitochondrial...
BACKGROUND
Amyotrophic lateral sclerosis (ALS) is a systemic disease with multiple pathological effects, including neuroinflammation, oxidative stress, autophagy, mitochondrial dysfunction, and endoplasmic reticulum stress. Despite many studies seeking to identify and develop effective therapies, effective ALS treatment has yet to be approved. Hence, patients with ALS ultimately experience muscle atrophy and loss of motor neurons. Herbal medicines have been used to treat numerous diseases by modulating multiple biological processes and exerting pharmacological effects, including anti-inflammatory and antioxidant properties. In particular, Koehne (CS) exhibits anti-hyperuricemic and nephroprotective effects and is used to treat anaphylaxis, viral infections, and neurodegenerative diseases, such as Alzheimer's disease. This study monitored the effects of CS supplementation on muscle function and motor neurons in hSOD1G93A mice, an established ALS animal model.
METHODS
Body weight measurements and behavioral tests were performed; additionally, western blotting and immunohistochemistry analyses were conducted using the mice gastrocnemius, tibialis anterior, and spinal cord.
RESULTS
CS augmented anti-inflammatory and antioxidant effects in the muscle and spinal cord of hSOD1G93A mice. Furthermore, CS improved motor function and regulated autophagy in the muscles of the hSOD1G93A mice.
CONCLUSIONS
CS might represent a promising supplement for improving motor function and delaying ALS progression. However, its development for clinical use warrants further investigation.
Topics: Humans; Mice; Animals; Amyotrophic Lateral Sclerosis; Mice, Transgenic; Disease Models, Animal; Spinal Cord; Rosaceae; Antioxidants; Plant Extracts
PubMed: 38179776
DOI: 10.31083/j.fbl2812326 -
Cellular and Molecular Life Sciences :... Jul 2023Cellular abscission is the final step of cytokinesis that leads to the physical separation of the two daughter cells. The scaffold protein ALIX and the ESCRT-I protein...
Cellular abscission is the final step of cytokinesis that leads to the physical separation of the two daughter cells. The scaffold protein ALIX and the ESCRT-I protein TSG101 contribute to recruiting ESCRT-III to the midbody, which orchestrates the final membrane scission of the intercellular bridge. Here, we addressed the transport mechanisms of ALIX and ESCRT-III subunit CHMP4B to the midbody. Structured illumination microscopy revealed gradual accumulation of ALIX at the midbody, resulting in the formation of spiral-like structures extending from the midbody to the abscission site, which strongly co-localized with CHMP4B. Live-cell microscopy uncovered that ALIX appeared together with CHMP4B in vesicular structures, whose motility was microtubule-dependent. Depletion of ALIX led to structural alterations of the midbody and delayed recruitment of CHMP4B, resulting in delayed abscission. Likewise, depletion of the kinesin-1 motor KIF5B reduced the motility of ALIX-positive vesicles and delayed midbody recruitment of ALIX, TSG101 and CHMP4B, accompanied by impeded abscission. We propose that ALIX, TSG101 and CHMP4B are associated with endosomal vesicles transported on microtubules by kinesin-1 to the cytokinetic bridge and midbody, thereby contributing to their function in abscission.
Topics: Cytokinesis; Kinesins; Biological Transport; Endosomal Sorting Complexes Required for Transport; Endosomes
PubMed: 37523003
DOI: 10.1007/s00018-023-04864-y -
Deutsches Arzteblatt International Mar 2024Approximately 9.9 % of children present with difficulties in language development (DLD), 7.6 % without serious additional impairments and 2.3 % associated with...
BACKGROUND
Approximately 9.9 % of children present with difficulties in language development (DLD), 7.6 % without serious additional impairments and 2.3 % associated with languagerelevant comorbidities, e.g., hearing loss. Notably, in a consensus statement by experts in German-speaking countries, in the guideline presented here, and further in this article, all of these disorders are referred to as "developmental language disorders" (DLD), whereas the international consortium CATALISE only refers to those without comorbidities as DLD. DLDs are among the most commonly treated childhood disorders and, if persistent, often reduce educational and socio-economic outcome. Children in their third year of life with developmental language delay (late talkers, LT) are at risk of a later DLD.
METHODS
This German interdisciplinary clinical practice guideline reflects current knowledge regarding evidence-based interventions for developmental language delay and disorders. A systematic literature review was conducted on the effectiveness of interventions for DLD.
RESULTS
The guideline recommends parent training (Hedges g = 0.38 to 0.82) for LTs with expressive language delay, language therapy (Cohen's d = -0.20 to 0.90) for LTs with additional receptive language delay or further DLD risk factors, phonological or integrated phonological treatment methods (Cohen's d = 0.89 to 1.04) for phonological speech sound disorders (SSDs), a motor approach for isolated phonetic SSDs (non-DLD), and for lexical-semantic and morpho-syntactic impairments combinations of implicit and explicit intervention approaches (including input enrichment, modeling techniques, elicitation methods, creation of production opportunities, metalinguistic- approaches, visualizations; Cohen's d = 0.89-1.04). Recom mendations were also made for DLD associated with pragmatic-communicative impairment, bi-/ multilingualism, hearing loss, intellectual disability, autism-spectrum disorders, selective mutism, language- relevant syndromes or multiple disabilities, and for intensive inpatient language rehabilitation.
CONCLUSION
Early parent- and child-centered speech and language intervention implementing evidence-based intervention approaches, frequency, and settings, combined with educational language support, can improve the effectiveness of management of developmental language delay and disorders.
Topics: Humans; Language Development Disorders; Germany; Language Therapy; Child, Preschool; Child; Male; Female; Practice Guidelines as Topic
PubMed: 38377329
DOI: 10.3238/arztebl.m2024.0004 -
Frontiers in Immunology 2023Amyotrophic lateral sclerosis (ALS) is a chronic, progressive neurodegenerative disease characterized by the loss of motor neurons. Dysregulated peripheral immunity has... (Review)
Review
Amyotrophic lateral sclerosis (ALS) is a chronic, progressive neurodegenerative disease characterized by the loss of motor neurons. Dysregulated peripheral immunity has been identified as a hallmark of ALS. Neutrophils, as the front-line responders of innate immunity, contribute to host defense through pathogen clearance. However, they can concurrently play a detrimental role in chronic inflammation. With the unveiling of novel functions of neutrophils in neurodegenerative diseases, it becomes essential to review our current understanding of neutrophils and to recognize the gap in our knowledge about their role in ALS. Thus, a detailed comprehension of the biological processes underlying neutrophil-induced pathogenesis in ALS may assist in identifying potential cell-based therapeutic strategies to delay disease progression.
Topics: Humans; Amyotrophic Lateral Sclerosis; Neutrophils; Neurodegenerative Diseases; Motor Neurons; Immunity, Innate
PubMed: 37662922
DOI: 10.3389/fimmu.2023.1246768