Effect of virtual reality-based seizure management education program for parents (VR-ESMEPP) on seizure management: A randomized controlled trial.

OBJECTIVE: This study evaluated the efficacy of Virtual Reality-Based Seizure Management Education Program for Parents (VR-ESMEPP) that was designed to improve parents' knowledge-skill percentage about epileptic seizure, and motivation levels about educational material. METHODS: The study was conducted at a university hospital's pediatric neurology clinic in Turkey and involved both a VR-trained group and a control group. The parents' knowledge-skill percentage about epileptic seizure, and motivation levels about educational material were assessed before, after, and at 15 days after participating in VR-ESMEPP. RESULTS: The parents' knowledge-skill percentage about epileptic seizure increased in the group that participated in the VR-ESMEPP. There was no such increase in the control group. Examination of the scores of the Instructional Materials Motivation Survey (IMMS) for the parents showed that while there was a significant increase between the pre-test and post-test within the group that participated in the VR-ESMEPP, there was no significant difference in the scores of the control group. However, the high IMMS scores obtained by all parents indicate the motivating nature of the education material. SIGNIFICANCE: The study established the efficacy of VR-ESMEPP and demonstrated its ability to enhance parents' knowledge-skill percentage about epileptic seizure. Despite the absence of a difference in motivation levels between the groups, the high scores obtained by all participants indicate that the program was indeed motivating.

Posttraumatic epilepsy in critically ill children with traumatic brain injury.

PURPOSE: The aim of this study was to determine the clinical, laboratory, and radiological factors related with posttraumatic epilepsy (PTE). METHODS: The study is a multicenter descriptive cross-sectional cohort study. Children who followed up for TBI in the pediatric intensive care unit between 2014 and 2021 were included. Demographic data and clinical and radiological parameters were recorded from electronic case forms. All patients who were in the 6-month posttraumatic period were evaluated by a neurologist for PTE. RESULTS: Four hundred seventy-seven patients were included. The median age at the time of trauma was 66 (IQR 27-122) months, and 298 (62.5%) were male. Two hundred eighty (58.7%) patients had multiple traumas. The mortality rate was 11.7%. The mean duration of hospitalization, pediatric intensive care unit hospitalization and mechanical ventilation, Rotterdam score, PRISM III score, and GCS at admission were higher in patients with epilepsy (p < 0.05). The rate of epilepsy was higher in patients with severe TBI, cerebral edema on tomography and clinical findings of increased intracranial pressure, blood transfusion in the intensive care unit, multiple intracranial hemorrhages, and intubated patients (p < 0.05). In logistic regression analysis, the presence of intracranial hemorrhage in more than one compartment of the brain (OR 6.13, 95%CI 3.05-12.33) and the presence of seizures (OR 9.75, 95%CI 4.80-19.83) were independently significant in terms of the development of epilepsy (p < 0.001). CONCLUSIONS: In this multicenter cross-sectional study, intracranial hemorrhages in more than one compartment and clinical seizures during intensive care unit admission were found to be independent risk factors for PTE development in pediatric intensive care unit patients with TBI.

Development of a conceptual framework for a Virtual Reality-based Seizure Management Education Program for Parents (VR-ESMEPP).

OBJECTIVE: Parents of children with epilepsy need support when managing epileptic seizures outside medical-care-center-settings. Previously developed training programs only provide information-based support. Therefore, within the scope of the VR-ESMEPP, a conceptual framework was developed in this study with the aim of developing parents' skills and motivation as well as providing them information regarding seizure management. METHODS: The conceptual framework of the VR-ESMEPP was developed in four steps. In step 1, a scenario was developed wherein a pediatric patient with epilepsy is having a seizure. The selected seizure type was "Focal to bilateral tonic-clonic" seizure, which is the most common and most skill-intensive type of tonic-clonic-seizure. In step 2, data collection tools related to epileptic seizure management were developed for parents. These tools included Child and Parent Introductory Form, Parental Information Assessment Form for Epileptic Seizure Management, and Parental Skills Assessment Form for Epileptic Seizure Management. In step 3, the conceptual framework and data collection tools developed were confirmed by a group of 10 specialists consisting of physicians and pediatric nurses working in the field of pediatric neurology. In step 4, the epileptic-pediatric-patient-scenario and data collection tools confirmed by experts were programmed into an application by a software company and integrated into virtual reality headsets. RESULTS: VR-ESMEPP with the conceptual framework described in the present study is a valid virtual reality-based program, which can be carried out under nurses' supervision and used to provide epilepsy-related education to parents. SIGNIFICANCE: VR-ESMEPP helped parents increase their knowledge and skills of epileptic seizure.

ATYPICAL MRI FINDINGS IN CEREBRAL ADRENOLEUKODYSTROPHY: A CASE REPORT.

Adrenoleukodystrophy is a rare X-linked hereditary disease that results in accumulation of very-long-chain fatty acids in all body tissues, thus causing demyelination of the white matter. Magnetic resonance imaging (MRI) is a reliable radiological modality to demonstrate the extension of brain lesions and severity of the disease. In the classic form, the parieto-occipital white matter is affected. Besides, atypical MRI findings such as primary frontal lobe involvement are rarely described. We report a case of adrenoleukodystrophy presenting with rare MRI findings such as bilateral symmetric frontal lobe white matter changes suggesting anterior predominance.

Correction: The genomic and clinical landscape of fetal akinesia.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The genomic and clinical landscape of fetal akinesia.

PURPOSE: Fetal akinesia has multiple clinical subtypes with over 160 gene associations, but the genetic etiology is not yet completely understood. METHODS: In this study, 51 patients from 47 unrelated families were analyzed using next-generation sequencing (NGS) techniques aiming to decipher the genomic landscape of fetal akinesia (FA). RESULTS: We have identified likely pathogenic gene variants in 37 cases and report 41 novel variants. Additionally, we report putative pathogenic variants in eight cases including nine novel variants. Our work identified 14 novel disease-gene associations for fetal akinesia: ADSSL1, ASAH1, ASPM, ATP2B3, EARS2, FBLN1, PRG4, PRICKLE1, ROR2, SETBP1, SCN5A, SCN8A, and ZEB2. Furthermore, a sibling pair harbored a homozygous copy-number variant in TNNT1, an ultrarare congenital myopathy gene that has been linked to arthrogryposis via Gene Ontology analysis. CONCLUSION: Our analysis indicates that genetic defects leading to primary skeletal muscle diseases might have been underdiagnosed, especially pathogenic variants in RYR1. We discuss three novel putative fetal akinesia genes: GCN1, IQSEC3 and RYR3. Of those, IQSEC3, and RYR3 had been proposed as neuromuscular disease-associated genes recently, and our findings endorse them as FA candidate genes. By combining NGS with deep clinical phenotyping, we achieved a 73% success rate of solved cases.

Evaluation of the efficiency of the web-based epilepsy education program (WEEP) for youth with epilepsy and parents: A randomized controlled trial.

BACKGROUND: When youth with epilepsy and their parents have insufficient information about the disease, they are known to have more problems with disease management, and they show poor compliance. Providing accurate, reliable, and accessible information with no time and space limitations is extremely important for individuals with epilepsy as well as for their caregivers. AIM: In this study, we aimed to evaluate the content, quality, usability, and efficacy of our web-based epilepsy education program (WEEP) that we developed for youth with epilepsy and their parents. METHODS: The sample of this randomized controlled trail was composed of youth with epilepsy who were between the ages of 9 and 18 years and their parents who had applied to the Pediatric Neurology Unit of a tertiary healthcare hospital in Turkey between November 2017 and April 2018. This study was conducted in two stages: (1) the preparation phase, during which we developed a WEEP for epilepsy, and tested its content, quality, and usability; and (2) the implementation phase, during which we evaluated the efficacy of the website by assessing users' knowledge of epilepsy, seizure self-efficacy, attitudes, and e-health literacy. Before the implementation phase, data collection tools were used to test the prior knowledge of epilepsy of the participants and control groups. Next, the youth and their parents were asked to use the WEEP for 12 weeks, while a control group was not provided with additional education tools. Written consent was obtained from the participants prior to the study in addition to obtaining approval from the ethics committee and permission from the institution where the research was conducted. The data were finally analyzed using SAS 9.4 software. RESULTS: During the preparation phase, the website was developed and tested for content, quality, and usability. The WEEP was graded 72.7 ±â€¯3.4 points by experts, 92.4 ±â€¯1.63 by youth with epilepsy, and 92.31 ±â€¯1.94 by the parents. During the implementation phase, the efficacy of the web site was evaluated through the assessment of participants' scores. We found that the mean knowledge, seizure self-efficacy, attitude, and e-health literacy scores of youth with epilepsy in the experimental group had significantly increased after the WEEP (p < 0.05). An increase in the scores of knowledge, anxiety, self-management, and e-health literacy scale was also found among the parents in the intervention group (p < 0.05). CONCLUSION: The content, quality, and usability of the WEEP were adequate and effective in improving knowledge, self-efficacy, attitudes, and e-health literacy of youth with epilepsy as well as those of their parents.

Tibial nerve axonal excitability in type 1 diabetes mellitus.

INTRODUCTION: The aim of this study was to determine alterations in axonal excitability in tibial nerve as compared with median nerve axonal excitability in patients with diabetic polyneuropathy. METHODS: Six patients with diabetic polyneuropathy and 10 patients with diabetes mellitus without polyneuropathy were enrolled. RESULTS: Compared with diabetic patients without polyneuropathy, the tibial nerve strength-duration time constant was significantly longer and supernormality was lower in those with polyneuropathy. Threshold electrotonus studies showed abnormalities in patients with diabetic polyneuropathy, in which smaller threshold changes from long-depolarizing and hyperpolarizing conditioning, termed "fanning-in," were found. DISCUSSION: This study confirms that axonal excitability is significantly altered in the tibial nerve of patients with diabetic polyneuropathy. Evaluating the axonal excitability of the median and tibial nerves may reveal the presence of length-dependent polyneuropathy at an early stage. Muscle Nerve 59:76-81, 2019.

Interleukin-12 (-1188) A/C and interferon-γ (+874) A/T gene polymorphisms in subacute sclerosing panencephalitis patients.

The two polymorphisms [IL-12 (-1188) A/C and the IFN-γ (+874) A/T)] are known to have functional consequences and henceforth were analyzed in subacute sclerosing panencephalitis (SSPE) patients to reveal a possible relation with these polymorphisms and this debilitating disease. For the IL-12 (-1188) A/C polymorphism, 78 patients and 90 healthy individuals were analyzed. An increase in the AA genotype was determined (p = 0.02, OR = 2.06). There was also a statistically significant difference between the control group and the patients with respect to the allele frequencies (p = 0.04, OR = 1.65). For the IFN-γ (+874) A/T polymorphism, 69 SSPE patients and 115 controls were studied and there was not a significant difference between the two groups. Our findings suggested that not the IFN-γ (+874) A/T but the IL-12 (-1188) A/C polymorphism is correlated with SSPE and having an AA genotype or A allele decreases the risk of developing SSPE by 2.06- and 1.65-fold, respectively.

Sensorimotor polyneuropathy in patients with SMA type-1: electroneuromyographic findings.

INTRODUCTION: Generally, spinal muscular atrophy (SMA) is believed to be a pure motor neuron disease. We retrospectively evaluated our electrodiagnostic findings in SMA type 1 patients to demonstrate co-existence of sensorimotor neuropathies. METHODS: Electroneuromyographic (ENMG) studies in 15 patients (11 boys, 4 girls) were reviewed independently by 2 neurophysiologists. Upper extremity findings were compared with normal right arm controls. RESULTS: Patient ages ranged from 1.5 to 26 months. Four SMA patients (26.7%) had decreased sensory nerve action potentials (SNAPs) or sensory nerve conduction velocities. Of them, median SNAPs could not be elicited in 3, and sural SNAPs could not be elicited in 2. Compound muscle action potential amplitudes were severely decreased in 14 (93.3%) and normal in 1. CONCLUSIONS: Survival motor neuron 1 (SMN1) gene analysis should be considered if clinical features are consistent with SMA, even if pathological or electrophysiological findings demonstrate peripheral sensorimotor polyneuropathies.

Determinants of Quality of Life after Pediatric Traumatic Brain Injury.

Introduction Pediatric traumatic brain injury (TBI) is a significant cause of death and long-term disability. There is a paucity of data on quality of life in survivors of pediatric TBI. The aim of this study is to determine the factors affecting the quality of life after TBI in children. Methods Consecutively admitted 104 of 156 patients to the pediatric intensive care unit (PICU) with TBI between 1 month and 18 years were included in the study. Demographics were obtained from electronic records. Injury severity and mortality scores were calculated. The Pediatric Quality of Life Inventory (PedsQL) scale and Glasgow Outcome Scale (GOS) score were evaluated by interview with patient or the caregiving parents. The Rotterdam computed tomography (CT) score was calculated from the radiology images taken within the first 24 hours after admission to the emergency service. Results Severe TBI, multiple trauma, intracranial hemorrhage from multiple sites, convulsions, high intracranial pressure, emergency operation on admission, and hypotension on admission were associated with low PedsQL values according to results of univariate analysis ( p < 0.05). There was a negative correlation between PedsQL and GOS, mechanical ventilation duration, PICU length of stay (LOS), and hospital LOS. In the linear regression model made by considering the univariate analysis results, it was shown that Rotterdam CT score and PICU LOS are independent variables that determine low PedsQL score. PedsQL scores were lower in children ≥ 8 years of age and in those evaluated within the first year after discharge ( p = 0.003). Conclusion In pediatric TBI, Rotterdam CT score and PICU LOS were found as independent variables determining PedsQL score after discharge.

Evaluation of exonic copy numbers of SMN1 and SMN2 genes in SMA.

SMA is a neuromuscular disease and occurs primarily through autosomal recessive inheritance. Identification of deletions in the SMN1 gene especially in the exon 7 and exon 8 regions (hot spot), are used in carrier testing. The exact copy numbers of those exons in the SMN1 and SMN2 genes in 113 patients who presented with a pre-diagnosis of SMA were determined using MLPA method. We aimed to reveal both the most common copy number profiles of different SMA types. It was found that the frequency of homozygous deletions in SMN1 was 15.9%, while heterozygous deletions was 16.9%. The most common SMN-MLPA profile was 0-0-3-3. In the cases with homozygous deletion, SMA type III diagnosis was observed most frequently (44%), and the rate of consanguineous marriage was found 33%. Two cases with the same exonic copy number profile but with different clinical subtypes were identified in a family. We also detected distinct exonic deletion and duplication MLPA profiles for the first time. We created "the SMA signature" that can be added to patient reports. Furthermore, our data are important for revealing potential local profiles of SMA and describing the disease in genetic reports in a way that is clear and comprehensive.

Clinical and Laboratory Features in Anti-NF155 Autoimmune Nodopathy.

BACKGROUND AND OBJECTIVES: To study the clinical and laboratory features of antineurofascin-155 (NF155)-positive autoimmune nodopathy (AN). METHODS: Patients with anti-NF155 antibodies detected on routine immunologic testing were included. Clinical characteristics, treatment response, and functional scales (modified Rankin Scale [mRS] and Inflammatory Rasch-built Overall Disability Scale [I-RODS]) were retrospectively collected at baseline and at the follow-up. Autoantibody and neurofilament light (NfL) chain levels were analyzed at baseline and at the follow-up. RESULTS: Forty NF155+ patients with AN were included. Mean age at onset was 42.4 years. Patients presented with a progressive (75%), sensory motor (87.5%), and symmetric distal-predominant weakness in upper (97.2%) and lower extremities (94.5%), with tremor and ataxia (75%). Patients received a median of 3 (2-4) different treatments in 46 months of median follow-up. Response to IV immunoglobulin (86.8%) or steroids (72.2%) was poor in most patients, whereas 77.3% responded to rituximab. HLA-DRB1*15 was detected in 91.3% of patients. IgG4 anti-NF155 antibodies were predominant in all patients; anti-NF155 titers correlated with mRS within the same patient (r = 0.41, p = 0.004). Serum NfL (sNfL) levels were higher in anti-NF155+ AN than in healthy controls (36.47 vs 7.56 pg/mL, p < 0.001) and correlated with anti-NF155 titers (r = 0.43, p = 0.001), with I-RODS at baseline (r = -0.88, p < 0.001) and with maximum I-RODS achieved (r = -0.58, p = 0.01). Anti-NF155 titers and sNfL levels decreased in all rituximab-treated patients. DISCUSSION: Anti-NF155 AN presents a distinct clinical profile and good response to rituximab. Autoantibody titers and sNfL are useful to monitor disease status in these patients. The use of untagged-NF155 plasmids minimizes the detection of false anti-NF155+ cases. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that anti-NF155 antibodies associate with a specific phenotype and response to rituximab.

Neurocognitive function in patients with ß-thalassemia major.

BACKGROUND: Children with ß-thalassemia major (ß-TM) have multiple risk factors for developing cognitive impairment. The aim of the present study was to evaluate cognitive function in patients with ß-TM. METHODS: Twenty children with ß-TM were enrolled into the study and were compared with a control group consisting of 21 healthy children. All participants were evaluated with neuropsychological tests and event-related potentials (ERP). RESULTS: All of the participants had normal IQ scores, but the patient group had significantly lower full-scale, performance, and verbal IQs compared with the control group (P < 0.05). The number of children with visuomotor dysfunction was higher in the patient group compared with the control group (P < 0.05). In the P300 test, the patient group had significantly prolonged N1, P2 and N2 latencies at the FZ, and a prolonged N1 latency at the Cz compared with the control group (P < 0.05). The patient group also had lower N1 and P3N4 amplitudes at the Fz, and lower N1, N1P2 and P3N4 amplitudes at the Cz when compared with the control group (P < 0.05). Mismatch negativity latency and duration were longer in the patient group (P < 0.05). CONCLUSIONS: Neuropsychological tests are safe, and reliable for the diagnosis of cognitive impairment in ß-TM patients, and the use of ERP may facilitate early diagnosis. The number of ß-TM patients in the present study was limited, however, and larger numbers of patients are required in further studies.

Changes of HMGB-1 and sTLR4 levels in cerebrospinal fluid of patients with febrile seizures.

PURPOSE: Fever-induced inflammatory processes and pro-inflammatory cytokines have gained importance in recent years in the pathogenesis of febrile convulsion. Increased levels of HMGB1 (high mobility group box 1), one of the most important pro-inflammatory cytokines, are associated with prolongation of seizure duration, recurrence of seizures and the development of epilepsy. Changes in the sTLR4 level (soluble toll-like receptor 4) in the cerebrospinal fluid (CSF) are thought to be associated with memory and learning functions. In our study, we aimed to evaluate changes in HMGB1 and sTLR4 levels in patients who had febrile seizures between 6 months and 6 years. METHODS: Forty patients who were admitted to Akdeniz University Medical Faculty Hospital between April 2016 and April 2018 with a complaint of febrile seizure and 45 patients whose CSF samples were taken for complaints other than febrile convulsion (control group) were included in our study. RESULTS: Comparison of the CSF HMGB1 levels of the febrile convulsion group and control group revealed a statistically significant increase in patients with febrile convulsions (p: 0.001). Comparison of the subgroups revealed that the mean value of CSF HMGB1 level was highest in the complex FS group with a mean value of 3363.9 ± 835,47 pg/mL. Comparison of the patient and control groups revealed that the changes in CSF sTLR4 levels were not statistically significant. CONCLUSION: HMGB1 level, a key inflammatory molecule, was significantly higher in the CSF of children with febrile seizures. Our data suggest that the HMGB1 network may contribute to the generation of febrile seizures in children.

Various Neurological Symptoms with Vitamin B12 Deficiency and Posttreatment Evaluation.

BACKGROUND: Vitamin B12 deficiency occurs primarily as a result of insufficient dietary intake in children in developing countries. Vitamin B12 deficiency produces a cluster of neurological symptoms in children. AIM: The aim of this study was to describe the vitamin B12 status of patients who were admitted with neurological symptoms and to evaluate the clinical response to vitamin B12 treatment. MATERIALS AND METHODS: This study was conducted on children who had vitamin B12 deficiency presented with neurological findings from January 2014 to October 2016. Patients with serum vitamin B12 levels lower than 300 pg/mL received intramuscular or oral vitamin B12 treatment. RESULTS: Three hundred and fifty-one patients presenting with neurologic symptoms and who had low serum vitamin B12 deficiency were analyzed. Our study population was composed mainly of adolescent age. The most common symptom with respect to age was headache. In infant patients, most common symptoms were seizure and developmental delay. CONCLUSION: Early diagnosis and vitamin B12 treatment are advocated to avoid long-term injury. Our study shows that patients with serum vitamin B12 levels lower than 300 pg/mL showed clinical improvement of neurological symptoms after receiving vitamin B12 treatment.

Bone metabolism markers and bone mineral density in children with neurofibromatosis type-1.

Some experimental studies suggested that there may be a bone formation defect rather than a disorder in bone resorption in patients NF1. The aim of this study was to determine bone mineral density (BMD) with dual-energy X-ray absorptiometry (DEXA) and investigate specific bone formation and bone resorption and bone turnover markers in children with NF1. Thirty-two children and adolescents (16 boys, 16 girls; 16 prepubertal, 16 pubertal) with NF1 were recruited. Their age ranged from 3 to 17 years. They were compared with matched healthy children. Dual-energy X-ray absorptiometry were applied to 26 patients and 27 controls. Nine of 32 subjects with NF1 had a skeletal abnormality. BMD of the lumbar spine, and femoral neck in NF1 patients significantly decreased compared to that of healthy subjects. They were also significantly decreased in pubertal patients when compared to pubertal controls and in prepubertal patients when compared to prepubertal controls. Patients with skeletal abnormalities were found to have significantly lower level of osteocalcin when compared to patients without skeletal abnormality. Other biochemical markers did not exhibit any difference between the groups. In conclusion, our findings suggest that bone formation markers rather than DEXA could be good predictors of skeletal abnormalities among NF1 patients. However, in our study the number of the NF1 patients with skeletal abnormality and the number of bone formation markers studied were all limited. It is appropriate to perform larger studies with other bone formation markers beside osteocalcin.

Spontaneous periodic hypothermia and hyperhidrosis.

We present a patient diagnosed with Shapiro syndrome without corpus callosum agenesis. A 4-year-old-girl was admitted to the hospital with complaints of sweating, cooling, and drowsiness that continued during the last week of her admission. Attacks occurred almost daily, and lasted for about 1 hour. All laboratory findings, as well as Holter and echocardiography results, were normal. Cranial magnetic resonance imaging demonstrated an intact corpus callosum, and electroencephalography obtained during an attack revealed normal findings. However, technetium 99m-labeled hexamethylpropylene amine oxime brain single-photon emission computed tomography indicated increased perfusion in the right thalamus, basal ganglia, and inferior frontal areas during a hypothermic period. Although oxcarbazepine reduced the frequency of attacks, they were not halted completely. The patient responded better to carbamazepine.

Electrophysiologic and neuropsychologic evaluation of patients with centrotemporal spikes.

The present study was designed to evaluate neurocognitive functions with endogenous potentials and neurophysiologic tests in patients with centrotemporal spikes who were not on any medication. Of the patients, 85.7% had seizures, 9.5% had pavor nocturnes, and 4.8% had atypical headache. The patients, especially who had atypical seizures or left-sided epileptic activity, were found to have significant visuomotor function impairment (p <.05). In P300 test, N2P3 amplitude was lower in the patients, particularly who had left sided epileptic activity (p <.05). MMN and LDN results were normal. Serial evaluations of such patients with endogenous potentials and neuropsychological tests may be helpful to show development of neurocognitive impairment.