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Objective: To define the phenotypic spectrum of phosphatidylinositol glycan class A protein (PIGA)-related congenital disorder of glycosylation (PIGA-CDG) and evaluate genotype-phenotype correlations., Methods: Our cohort encompasses 40 affected males with a pathogenic PIGA variant. We performed a detailed phenotypic assessment, and in addition, we reviewed the available clinical data of 36 previously published cases and assessed the variant pathogenicity using bioinformatical approaches., Results: Most individuals had hypotonia, moderate to profound global developmental delay, and intractable seizures. We found that PIGA-CDG spans from a pure neurological phenotype at the mild end to a Fryns syndrome-like phenotype. We found a high frequency of cardiac anomalies including structural anomalies and cardiomyopathy, and a high frequency of spontaneous death, especially in childhood. Comparative bioinformatical analysis of common variants, found in the healthy population, and pathogenic variants, identified in affected individuals, revealed a profound physiochemical dissimilarity of the substituted amino acids in variant constrained regions of the protein., Significance: Our comprehensive analysis of the largest cohort of published and novel PIGA patients broadens the spectrum of PIGA-CDG. Our genotype-phenotype correlation facilitates the estimation on pathogenicity of variants with unknown clinical significance and prognosis for individuals with pathogenic variants in PIGA., (© 2020 International League Against Epilepsy.)

Background: Glycosylphosphatidylinositol biosynthesis defects (GPIBDs) cause a group of phenotypically overlapping recessive syndromes with intellectual disability, for which pathogenic mutations have been described in 16 genes of the corresponding molecular pathway. An elevated serum activity of alkaline phosphatase (AP), a GPI-linked enzyme, has been used to assign GPIBDs to the phenotypic series of hyperphosphatasia with mental retardation syndrome (HPMRS) and to distinguish them from another subset of GPIBDs, termed multiple congenital anomalies hypotonia seizures syndrome (MCAHS). However, the increasing number of individuals with a GPIBD shows that hyperphosphatasia is a variable feature that is not ideal for a clinical classification., Methods: We studied the discriminatory power of multiple GPI-linked substrates that were assessed by flow cytometry in blood cells and fibroblasts of 39 and 14 individuals with a GPIBD, respectively. On the phenotypic level, we evaluated the frequency of occurrence of clinical symptoms and analyzed the performance of computer-assisted image analysis of the facial gestalt in 91 individuals., Results: We found that certain malformations such as Morbus Hirschsprung and diaphragmatic defects are more likely to be associated with particular gene defects (PIGV, PGAP3, PIGN). However, especially at the severe end of the clinical spectrum of HPMRS, there is a high phenotypic overlap with MCAHS. Elevation of AP has also been documented in some of the individuals with MCAHS, namely those with PIGA mutations. Although the impairment of GPI-linked substrates is supposed to play the key role in the pathophysiology of GPIBDs, we could not observe gene-specific profiles for flow cytometric markers or a correlation between their cell surface levels and the severity of the phenotype. In contrast, it was facial recognition software that achieved the highest accuracy in predicting the disease-causing gene in a GPIBD., Conclusions: Due to the overlapping clinical spectrum of both HPMRS and MCAHS in the majority of affected individuals, the elevation of AP and the reduced surface levels of GPI-linked markers in both groups, a common classification as GPIBDs is recommended. The effectiveness of computer-assisted gestalt analysis for the correct gene inference in a GPIBD and probably beyond is remarkable and illustrates how the information contained in human faces is pivotal in the delineation of genetic entities.

Epilepsy surgery has been established as an effective treatment in pharmacoresistant focal epilepsies. Most candidates for epilepsy surgery are patients with partial epilepsy syndromes refractory to medical treatment. The curative surgery procedure is resection of the epileptogenic zone; therefore, precise detection of the site responsible for seizure generation is necessary. Modern structural and functional imaging techniques have made presurgical evaluation less invasive and available for a higher number of patients. Video electroencephalography (EEG) monitoring, high-resolution structural and functional imaging techniques are used widely for presurgical evaluation. When noninvasive evaluation is not sufficient for the detection of the epileptogenic zone, invasive EEG monitoring and intracarotid amobarbital test are used. A classical example of a surgically curable epilepsy syndrome is mesial temporal lobe epilepsy with about 70-80% of patients becoming free of seizures after surgery. Results in extratemporal epilepsies are also satisfactory. Despite worldwide expansion during the recent decade, epilepsy surgery remains underutilized. Better understanding of advances in presurgical evaluation should reduce fears of epilepsy surgery and help to select patients who could achieve complete seizure control or significant amelioration after surgery.

The aim of this controlled historical cohort study was to assess the validity of post-concussion syndrome in children. We identified 301 children aged 4-15 years who had sustained an isolated brain concussion, and another group of 301 children who sustained any other mild body injury excluding the head. Parents from both groups filled in standardized questionnaires containing questions about the health condition of the children: headache, neck pain, dizziness, malaise, fatigability, exercise or noise intolerance, irritability, weepiness, sadness, anxiety, nocturnal enuresis, tics, sleep disorders, memory or learning difficulties, hyperactivity, seizures, attention disorder, buzzing in the ears, subjective parental concerns about the child's health condition, and parental concerns about their child having a brain disorder. The severity of the complaints was rated on the Visual Analogue Scale. After the final exclusion, 102 pairs strictly matched by sex, age, and the date of trauma were analyzed. The differences of parental complaints about the health condition of their children between case and control groups were statistically insignificant for all symptoms, except parental concerns about their child having brain damage which were significantly higher in the case group. The likelihood of parental concerns about the possibility of their child having brain damage was 2.7 times higher in the case group. Headache, learning difficulties, and sleep disorders were significant variables predicting the concerns. These results question the validity of the post-concussion syndrome in children.

Psychosocial adjustment of adolescents with health disorders has been studied extensively. However, it is unclear whether different health disorders have specific impact on adjustment, or disorder in general relates to the development of adjustment difficulties as a factor limiting adolescent's physical and social activity. This study was aimed to identify peculiarities of psychosocial adjustment difficulties among hospitalized adolescents with neurological and physical disorders and secondary school students. The sample consisted of 738 adolescents (aged 12-18 years), of which 100 had neurological and 94 - physical disorders, and 544 secondary school students. Psychosocial adjustment difficulties were evaluated using Standardized Interview for the Evaluation of Adolescents' Problems. Results show that emotional-mood difficulties and low self-esteem are more prevalent and severe in the clinical groups comparing with the healthy controls, while the prevalence and the severity of conflicts are higher among students. Comparison of both clinical groups shows that neurological disorders are related to higher prevalence of difficulties in emotional and cognitive functioning and higher severity of suicidal tendencies, while physical disorders relate to higher prevalence of behavior difficulties.

Objective: To investigate the clinical features and the prevalence of symptoms of post-concussion syndrome in children with mild traumatic brain injury, and to evaluate their changes over time., Material and Methods: The research involved two groups of 4-16 year-old children: the case group of 301 children who had experienced a single mild traumatic brain injury, and the control group of 301 children who had sustained any other mild body injury without head trauma. Groups were matched according to gender, age, and the date of admission to hospital. In total, 102 matched pairs were analyzed. The period between the date of the trauma and the examination was one to five years (median-27 months). Standardized questionnaires were sent by post to parents from both groups. Parents were asked about the health state as well as symptoms of post-concussion syndrome, their character and frequency. The respondents were inquired about the presence of the symptoms prior to the trauma, shortly after the trauma, and during the last year and the last month before the inquiry., Results: The prevalence of headache, irritability, fears, sleep disorders, learning difficulties, as well as concentration and memory problems did not differ significantly between children with mild traumatic brain injury and the control group when the results of the last year before examination and the last month before the examination were compared. We have investigated how the period of time between the date of the trauma and the date when the questionnaire was filled in influenced the results. The comparison of the questionnaires that were filled a year (but less than two years) after the trauma to those that were filled in 2-5 years after the trauma revealed significant differences in the prevalence of a number of symptoms of the post-concussion syndrome. In children with mild traumatic brain injury, there was a significant decrease in the prevalence of learning difficulties soon after the trauma (p=0.032), headaches before (p=0.026) and soon after the trauma (p=0.01), and irritability the last month before the examination (p=0.043). In children from the control group, there was a significant decrease in the prevalence of concentration problems the last year before examination (p=0.023) and the last month before examination (p=0.036)., Conclusions: More than one year after the trauma, the prevalence of the symptoms of the post-concussion syndrome is not significant higher in children with mild traumatic brain injury, compared to children with other mild body injuries, and is comparable by the changes over time.

Unlabelled: The aim of the study was to investigate the prevalence and clinical features of headaches and their accompanying signs in children with mild traumatic brain injury, as well as to evaluate their changes over time., Material and Methods: The research involved two groups of 4-16 year-old children: the case group of 301 children who had experienced a single mild traumatic brain injury, and the control group--301 children who had suffered from any other mild body injury without head trauma. Groups were matched according to gender, age, date of admission to hospital. The period between the date of trauma and examination was at least one year (median 7 months). Standardized questionnaires were sent by post to parents from both groups. Parents were asked about character, frequency, dizziness and concomitant symptoms. In total, 102 matched pairs were analyzed., Results: During the year before the filling in the questionnaires 114 (57.3%) parents indicated headaches: 64 (62.7%) in the case, and 50 (49%) in control group. Frequent (> or =8 days per month) headaches prevailed in children with mild traumatic brain injury (p=0.039); however, their prevalence decreased from 43.8% to 12.5% (p=0.01) with increasing time interval between the date of trauma and the inquiry. By the character, duration, intensity of the headaches, none of the features (except dizziness) showed any difference between the groups. Thirty-three (51.6%) parents from the case and 16 (32%) from the control group indicated that dizziness accompanied headaches (p=0.036). Forty-five (44.1%) parents from the case group and 28 (27.5%) parents from the control group indicated that dizziness appeared separately from headaches (p=0.013). According to the data for the last month before the inquiry, there was no statistically significant difference between both groups when estimating the dynamics in time., Conclusions: Headaches are not more prevalent in children with mild traumatic brain injury, compared to children with other mild body injuries. The frequency of headaches, as well as the prevalence of dizziness in children with mild traumatic brain injury decreases with time.

The prevalence of epilepsy in children aged 0-15 years of Kaunas city, Lithuania, was evaluated on 1 January 1995. Multiple sources for case identification were used, i.e. medical records at the university hospital, regional outpatient clinics and consultation centres, institutions, schools and kindergartens for the handicapped. Active epilepsy was defined as two or more unprovoked epileptic seizures with at least one seizure occurring within the previous 5 years, regardless of the antiepileptic drug treatment. Prevalence was found to be 4.25 (3.42, if age-standardized) in 1000. The highest rate was found in the 10-14 years age group. The male/female ratio was 1.29. No possible causes could be determined in 60.3% of cases. Congenital causes were diagnosed in 18.8% of cases, perinatal causes in 15.3%, traumatic causes in 2.6% and neuroinfectious causes in 2.4%. Classification of epilepsies and epileptic syndromes [Commission on Classification and Prognosis of the International League Against Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia 1989; 30:389-399] revealed that 50% of cases were localization-related epilepsies, 29.9% were generalized epilepsies, 15.9% were undetermined whether partial or generalized and 4.2% were unclassifiable. Rates for idiopathic, symptomatic and cryptogenic cases are presented.