Expressive Speech Disorder Research Articles

Current Approaches to Assessing the Safety and Efficacy of Lamotrigine in Children and Adolescents with Epileptic Syndromes Associated with Focal Seizures

Scientific relevance. Epileptic syndromes associated with focal seizures often develop in children and adolescents and may be accompanied by cognitive impairment, mental disorders, and endocrine disorders, which require additional medication apart from anti-epileptic medicinal products. Currently, the selection of safe and effective therapies for epileptic syndromes, especially in paediatric populations, is a pressing challenge for epileptology.Aim. This study aimed at a comprehensive assessment of the safety and efficacy of lamotrigine in therapeutic doses for children and adolescents with epileptic syndromes associated with focal seizures.Materials and methods. A total of 53 patients aged 3 to 18 years with various epileptic syndromes associated with focal seizures were under observation in 2020–2023. During this period, 37 patients (69.8%) received monotherapy with lamotrigine, and 16 patients (30.2%) received combination therapy including lamotrigine and two or more other medicinal products. When evaluating the safety and efficacy of pharmacotherapy in adolescent patients, the authors selectively used the Software for Post-marketing Studies of Anti-epileptic Medicinal Products developed at the Scientific Centre for Expert Evaluation of Medicinal Products.Results. With lamotrigine, the highest rate of complete clinical remission was observed in patients with focal epilepsy with onset in childhood and adolescence (90.9% of cases). For structural focal epilepsy, 16.7% of patients achieved complete freedom from seizures, and 50% demonstrated a pronounced response to treatment. However, patients with epilepsy due to local structural changes in the neocortex (33.3% of cases) had a prognosis of severe epilepsy. For epileptic encephalopathies with onset in childhood, 66.7% of patients achieved a ≥50% reduction in the frequency of seizures. Seizure reduction improved the quality of life of patients and their parents, especially of those with a long history of unsuccessful treatment attempts. There were no adverse reactions associated with lamotrigine except those listed in the summary of product characteristics. The Software for Post-marketing Studies of Anti-epileptic Medicinal Products provided a means for scoring and plotting the changes in the condition of adolescents without severe cognitive and memory impairment undergoing lamotrigine treatment.Conclusions. According to the study results, lamotrigine is highly effective and has a favourable safety profile in patients with early-onset epileptic syndromes associated with focal seizures. Moreover, lamotrigine is applicable to the treatment of attention, memory, expressive speech disorders, and aggressive behaviour. Therefore, lamotrigine may be recommended for treating children and adolescents with comorbid epileptic syndromes and cognitive and emotional disorders. Specialised software improves the quality of real-world evidence regarding the safety and efficacy of anti-epileptic medication.

Cognitive speech disorders in children with congenital heart defects aged 5–7 years

Purpose. To found out expressive speech disorders as a sign of neurocognitive development delay in children with congenital heart defects before and after surgery. Material and methods: 216 children with congenital heart defects were divided into groups according to the presence (group 1, n = 71) and absence (group 2, n = 145) of family history confounding factors, and studied before surgery and in 1 and 2 years after definitive repair under cardiopulmonary bypass. The anamnesis, clinical and hemodynamic aspects were studied before and after surgery, mental status and expressive speech diagnostics were also performed. Results. The predictors of neurocognitive impairment in children with congenital heart defects before surgery were identified: the level of heart failure, comorbidity, burdened family history. 76.3 % of children had «average» level of neurocognitive development (more in group 2) in a year after surgical correction, while 23.6 % had «low» and «very low» level (more in group 1); there were general expressive speech disorders in 68 % children in group 1 and in 55 % in group 2 among all children. «High» level of neurocognitive development was recorded in 2 years (13.8 % among all children), while the number of children with general expressive speech disorders was approximately the same despite of positive dynamic of clinical and hemodynamic aspects. Conclusion. There are «low» levels of neurocognitive development and expressive speech disorders in children with congenital heart defects in long term postoperative period despite of clinical and hemodynamic normalization. It can predict significant risks and poor quality of life in the absence of timely correction.

De novo stop-loss variants in CLDN11 cause hypomyelinating leukodystrophy.

Claudin-11, a tight junction protein, is indispensable in the formation of the radial component of myelin. Here, we report de novo stop-loss variants in the gene encoding claudin-11, CLDN11, in three unrelated individuals presenting with an early-onset spastic movement disorder, expressive speech disorder and eye abnormalities including hypermetropia. Brain MRI showed a myelin deficit with a discrepancy between T1-weighted and T2-weighted images and some progress in myelination especially involving the central and peripheral white matter. Exome sequencing identified heterozygous stop-loss variants c.622T>C, p.(*208Glnext*39) in two individuals and c.622T>G, p.(*208Gluext*39) in one individual, all occurring de novo. At the RNA level, the variant c.622T>C did not lead to a loss of expression in fibroblasts, indicating this transcript is not subject to nonsense-mediated decay and most likely translated into an extended protein. Extended claudin-11 is predicted to form an alpha helix not incorporated into the cytoplasmic membrane, possibly perturbing its interaction with intracellular proteins. Our observations suggest that stop-loss variants in CLDN11 expand the genetically heterogeneous spectrum of hypomyelinating leukodystrophies.

CHANGES OF THE LOCAL FUNCTIONAL BRAIN ACTIVITY ASSOCIATED WITH SPEECH DISORDERS IN CHILDREN WITH EPILEPSY AND DEVELOPMENTAL DELAY (PET STUDY)

PET study of cerebral glucose metabolism was performed in 73 children with epilepsy and mental retardation. Expressive speech disorders were associated with decrease of cerebral metabolism rate of glucose (CMRglu) in the upper frontal gyrus, caudate nucleus and thalamus of the left and right hemispheres. In the group with combined expressive and impressive speech disorders the significant CMRglu reduction in the middle temporal and supramarginal gyrus of the left hemisphere was observed. The obtained results confirm that the brain structures associated with the executive functions and complex association processes have a great significance in the speech development.

Autosomal Recessive Primary Microcephaly (MCPH): An Update.

Autosomal recessive primary microcephaly (MCPH; MicroCephaly Primary Hereditary) is a genetically heterogeneous neurodevelopmental disorder characterized by a significantly reduced head circumference present already at birth and intellectual disability. Inconsistent features include hyperactivity, an expressive speech disorder, and epilepsy. Here, we provide a brief overview on this rare disorder pertinent for clinicians.

A Syndromic Neurodevelopmental Disorder Caused by De Novo Variants in EBF3

Early B cell factor 3 (EBF3) is a member of the highly evolutionarily conserved Collier/Olf/EBF (COE) family of transcription factors. Prior studies on invertebrate and vertebrate animals have shown that EBF3 homologs are essential for survival and that loss-of-function mutations are associated with a range of nervous system developmental defects, including perturbation of neuronal development and migration. Interestingly, aristaless-related homeobox (ARX), a homeobox-containing transcription factor critical for the regulation of nervous system development, transcriptionally represses EBF3 expression. However, human neurodevelopmental disorders related to EBF3 have not been reported. Here, we describe three individuals who are affected by global developmental delay, intellectual disability, and expressive speech disorder and carry de novo variants in EBF3. Associated features seen in these individuals include congenital hypotonia, structural CNS malformations, ataxia, and genitourinary abnormalities. The de novo variants affect a single conserved residue in a zinc finger motif crucial for DNA binding and are deleterious in a fly model. Our findings indicate that mutations in EBF3 cause a genetic neurodevelopmental syndrome and suggest that loss of EBF3 function might mediate a subset of neurologic phenotypes shared by ARX-related disorders, including intellectual disability, abnormal genitalia, and structural CNS malformations.

Glucose Transporter-1 (GLUT1) Deficiency Syndrome: Diagnosis and Treatment in Late Childhood

Typical cases of glucose transporter-1 deficiency syndrome (GLUT1-DS) present with early-onset epilepsy. We report symptoms, diagnostic results, and effects of therapy in two patients diagnosed with GLUT1-DS at the age of 10 and 15 years, respectively. Patient 1: After four cerebral seizures in the first 2 years of life the patient was seizure-free but showed a complex movement disorder, expressive speech disorder, and mental retardation. Ratio of cerebrospinal fluid (CSF) to blood glucose was 0.41 (reference range 0.65 ± 0.1), molecular genetic testing confirmed GLUT1 deficiency with the novel pathogenic mutation c.1377dupC (p.Phe460LeufsX3) in the SLC2A1 gene. Following 9 months of ketogenic diet started at the age of 10 years, there was distinct improvement of speech and movement disorder. Patient 2 showed pharmacorefractive epilepsy, mental retardation, and a mild movement disorder. At the age of 15 years, extensive intake of food with high fat content was observed. Ratio of CSF to blood glucose was 0.41 (reference range 0.65 ± 0.1). The pathogenic mutation c.634C>T (p.Arg212Cys) was found in the SLC2A1 gene. Self-induced high-fat diet can be a hint toward GLUT1-DS. Ketogenic diet can be beneficial even when started in late childhood, although it may take several months to achieve a positive effect.

P03-86 The disorders of emotional and volitional spheres in preschool children with speech pathology

Objective:To study the peculiarity of emotional and volitional spheres in preschool children with speech pathology.Methods:250 children aged from 2 to 7 years old with speech pathology were examined. the following kinds of speech disorders were educed: impressive speech disorders - 9,2 %, expressive speech disorders - 31,2%, mixed speech disorders - 59,6 %. Due to the seriousness of the speech disorders the children were divided into 3 groups.Results:The educed disorders develop in the following psychopathological syndromes: neurotic, autism-like, hyperdynamic. in 62% of children with impressive speech disorders the autism-like syndrome was marked, and in 38 % both the autism-like and the hyperdynamic syndromes. in 74 % of children with expressive speech disorders the hyperdynamic syndrome was marked and in 26 % the neurotic syndrome. All the 3 syndromes were educed in children with mixed speech disorders however if in the structure of speech disorder a sensorial component prevailed then the autism-like syndrome was found. with the predominance of a motor component there were both hyperdynamic and neurotic syndromes. Direct dependence of intensity of these syndromes on seriousness of speech disorders was educed.Conclusions:The results of the research show, that children with speech pathology at preschool age have already the disorders of emotional and volitional spheres which influences the development of the personality of a child and contributes to the reinforcement of negative forms of reaction.