Neuropediatrics最新文献

Prenatal alcohol exposure causes disruptions in brain development. The resulting disorder, fetal alcohol spectrum disorder (FASD), cannot be cured, but interventions can help improve the daily functioning of affected children and adolescents and the quality of life for the entire family.The aim of the German guideline version 2024 is to provide validated and evidence-based recommendations on interventions for children and adolescents with FASD.We searched for international guidelines and performed a systematic literature review and a hand search to identify literature (published 2012-2022) on interventions for children (0-18 years) with FASD. The quality of the literature was assessed for predefined outcomes using the GRADE method (grading of recommendations, assessment, development, and evaluation). We established a multidisciplinary guideline group, consisting of 15 professional societies, a patient support group, and 10 additional experts in the field. The group agreed on recommendations for interventions based on the systematic review of the literature and formulated additional recommendations, based on clinical experience/expert evidence in a formal consensus process.No international guideline focusing on interventions for patients with FASD was found. Thirty-two publications (4 systematic reviews and 28 original articles) were evaluated. The analysis resulted in 21 evidence-based recommendations and 26 expert consensus, covering the following topics: neuropsychological functioning, adverse effects of therapy, complications/secondary conditions, quality of life, caregiver burden, knowledge of FASD, and coping and self-efficacy.The German guideline is the first internationally to provide evidence-based recommendations for interventions in children and adolescents with FASD.

Background: Infantile epileptic spasms syndrome (IESS) is the most common epileptic encephalopathy in infancy and early childhood. At present, adrenocorticotropic hormone (ACTH) and prednisolone are commonly used as drug treatment regimens for IESS. However, evidence of efficacy and economics remains controversial. This study aimed to evaluate the effectiveness, safety, and economy of ACTH and prednisolone of IESS.

Methods: Seven literature databases and two clinical trial registration platforms were searched, and a meta-analysis was conducted. From the perspective of the health care system, a 14-day economic evaluation was conducted. The rate of spasm cessation on the 14th day was used as the effect index. The univariate sensitivity analysis was used to verify the robustness of the results.

Results: Nine randomized controlled trials (RCTs) were included. Current clinical evidence is not sufficient to prove the difference in the rate of spasm cessation on the 14th day (risk ratio [RR] = 1.05, 95% CI 0.86-1.27, p = 0.64) and total adverse event rate (RR = 0.87, 95% CI 0.53-1.42, p = 0.57). ACTH had an advantage in improving electroclinical response on the 14th day (RR = 1.46, 95% CI 1.09-1.96, p = 0.01) and reducing the number of months taken for relapse (mean difference = 1.65, 95% CI 1.01-2.29, p < 0.01). The cost of ACTH and prednisolone was 5,629.19 yuan and 5.56 yuan, respectively. Univariate sensitivity analysis showed the most influential factor was the cost of ACTH.

Conclusions: There is insufficient evidence to determine whether ACTH or prednisolone is better in the short-term regimen of IESS. ACTH may have more advantages in improving the long-term outcome of IESS. In China, a prednisolone regimen of IESS has a lower cost within 14 days.

Objective: Infantile spasms (IS) are an age-specific epilepsy syndrome associated with poor outcomes. Sustained and early spasm control remains the main goal of therapy. We aimed to evaluate a unique pulsatile dexamethasone therapy regime in children with IS.

Methods: Children with IS were treated with oral pulsatile-applied dexamethasone in the Children's Hospital Jena between 2002 and 2021, regardless of duration since IS onset or previous therapy (except ACTH). A prolonged initial pulse was given in case of insufficient response (standard: 5-7 days, prolonged: 10-14 days). We analyzed spasm reduction, electroencephalographic response, adverse reactions, neurodevelopmental status, and epileptic disorders at the last follow-up.

Results: Included were 26 patients with a median age of 5.5 months (interquartile range 4-8) at IS onset and a mean follow-up of 6.2 years (standard deviation [SD] 3.99). Fifty percent had an unknown etiology. Patients received on average 10.8 pulses (SD 6.0); 69.2% achieved initial seizure freedom, however, 38.9% relapsed. Seventeen patients had an initial prolonged pulse, of those, 14 got initially seizure-free (82.4%). Sixty-four percent of the cases had a sustained spasm cessation after the third pulse. At the last follow-up, half of the patients had no persisting epileptic disorder; 22.2% had a favorable neurocognitive development. Patients with unknown etiology were more likely to achieve seizure freedom during therapy (p = 0.025), had a more favorable neurocognitive outcome (p = 0.049), and were less likely to suffer from epileptic disorders (p = 0.037). No serious adverse effects were observed.

Conclusion: Our results show that our treatment is safe and leads to outcomes comparable to usually applied hormonal therapy regimes. Etiology remains the most influential factor.

Ceroid lipofuscinosis type 2 (CLN2) is caused by biallelic pathogenic variants in the TPP1 gene, encoding lysosomal tripeptidyl peptidase 1 (TPP1). The classical late-infantile phenotype has an age of onset between 2 and 4 years and is characterized by psychomotor regression, myoclonus, ataxia, blindness, and shortened life expectancy. Vision loss occurs due to retinal degeneration, usually when severe neurological symptoms are already evident.Intracerebroventricular enzyme replacement therapy (ICV-ERT) using recombinant human TPP1 (rhTPP-1) was shown to slow the neurological decline; however, it does not prevent loss of vision. Intravitreal rhTPP-1 (IVT-ERT) was described to halt retinal degeneration in a canine CLN2 model and a compassionate-use study in humans.We report on the clinical and ophthalmological outcome in an early-treated patient homozygous for a pathogenic variant in TPP1 known to be associated with severe CLN2 retinopathy.He was started on ICV-ERT at the age of 40 months and 4 weekly IVT-ERT in one eye at the age of 60 months. The other eye served as untreated control.Baseline best corrected visual acuity (BCVA) was 0.5 with mild bull's eye maculopathy evident in both eyes. After 24 months of IVT-ERT, BCVA in the treated eye was 0.2 with bull's eye maculopathy sparing outer retinal layers, whereas the untreated eye had progressed to endstage retinopathy and BCVA <0.02. No intraocular side effects occurred.Our results provide further evidence that IVT-ERT appears to be safe and markedly delays retinal degeneration preserving visual function and increasing the patient's quality of life, especially if started early.

Hemimegalencephaly (HME) is a rare congenital disorder that is initiated during embryonic development with abnormal growth of one hemisphere. Tuberous sclerosis complex (TSC), a genetic disorder, is rarely associated with HME.We present a case of a newborn with HME with a confirmed mutation in the TSC-1 gene and describe the clinical course, findings on amplitude-integrated electroencephalography (aEEG), cranial ultrasound (CUS), MRI, and the postmortem evaluation. Furthermore, we conducted a comprehensive literature review of all reported newborns with HME and a genetically confirmed TSC mutation.This infant experienced therapy-resistant seizures after birth despite treatment with multiple antiseizure medications. CUS and MRI revealed HME of the left hemisphere. Early functional hemispherectomy, around the age of 3 months, was considered but dismissed after multidisciplinary evaluation, medical ethical consultation, and multiple discussions with the parents. Care was redirected due to worsening clinical and neurologic conditions, increasing respiratory insufficiency, and ongoing therapy-resistant seizures. Postmortem evaluation of the brain revealed hamartomatous brain changes and irregular gyration of the enlarged hemisphere. in addition, these changes were also present in the previously considered unaffected side, raising thoughts about the potential effectiveness of functional hemispherectomy.This case report illustrates that in cases with TSC abnormalities might not be confined solely to the initially considered affected side. This can have important therapeutic implications.

Progressive myoclonus epilepsy (PME) is a rare, clinically and genetically heterogeneous epilepsy syndrome, and pathogenic variants in the semaphorin 6B (SEMA6B) gene have recently been reported to be among the causes of PME. Cases with pathogenic variants in the SEMA6B gene are extremely rare, only a limited number of cases have been reported in the literature. In this systematic review, we aimed to present a summary of a PME case in which a heterozygous nonsense variant of c.2086C > T p.(Gln696*) in the SEMA6B gene was detected in the etiology and other cases with SEMA6B pathogenic variant in the literature. Except for our case, 35 cases from 12 studies were included. The main clinical findings in these patients were cognitive problems, seizures, gait and speech disturbances, and cognitive and/or motor regression, and they had a wide spectrum of severity. Response to antiseizure medications was also highly variable, almost half of the patients had pharmacoresistant seizures. Patients were divided into four different phenotypic groups according to their clinical presentations: PME (18/36), developmental and epileptic encephalopathy (13/36), neurodevelopmental disorder (4/36), and epilepsy (1/36), respectively. In conclusion, although SEMA6B has been associated with PME, it may actually cause a much broader phenotypic spectrum. Due to their extreme rarity, our knowledge of SEMA6B-related disorders is limited. As with all other rare diseases, each new SEMA6B-related disorder case could contribute to a better understanding of the disease. A better understanding of the disease may allow the development of specific treatment options in the future.

Background: Global developmental delay (GDD) is a common pediatric disorder that affects up to 3% of children. Due to the heterogeneous etiology of GDD, diagnostic procedures and algorithms are complex and diverse. The aim of our study was to investigate the diagnostic yield of genetic, metabolic, and imaging studies in establishing the etiology of unexplained GDD (UGDD).

Methods: In this retrospectively observational study, we examined the medical records of all children diagnosed with UGDD at the Department of Pediatric Neurology, University Medical Centre Ljubljana, Slovenia, between January and December 2019. We evaluated the effectiveness of various genetic, metabolic, and magnetic resonance imaging (MRI) tests in identifying the underlying cause of GDD. Additionally, we assessed subgroups of patients to determine whether any of the studied tests were particularly beneficial based on their clinical symptoms.

Results: A total of 123 patients met the inclusion criteria, with a median age of 4.3 years (range, 0-16 years), of which 71 (57.7%) were males. Genetic diagnosis was established in 47.1% (58/123) of patients. Metabolic laboratory testing did not identify a metabolic disease in any of the tested participants (114/123) and MRI was critical for diagnosis in only 1/81 (1.2%) patient.

Conclusion: Our findings strongly suggest that genetic testing surpasses MRI and metabolic testing in establishing the etiology of UGDD in a pediatric neurology outpatient setting. This information will help guide the diagnostic evaluation of these children.

Objective: The study aimed to interpret and establish patterns of amplitude-integrated electroencephalogram (aEEG) in stable preterm neonates and compare the aEEG among different gestational age groups using three standard classifications.

Methods: This prospective cohort study included stable preterm neonates between 24^0/7 and 36^6/7 weeks of gestation. aEEG was recorded in the first and second week of life and interpreted using the L. Hellström-Westas, Burdjalov, and Magalhães classification for background pattern, continuity, upper and lower margin amplitude, sleep-wake cycle, bandwidth, and presence of seizures. Subgroup analysis was performed based on ≤30 and >30 weeks' gestation.

Results: A total of 76 aEEG recordings were analyzed from 45 preterm neonates. In the first week, 60% of the neonates had normal voltage patterns, which increased to 80% in the second week. All infants ≤30 weeks displayed discontinuous wave patterns during the first week, and half transitioned to continuous waves in the second week. The lower margin amplitude increased, and the upper margin amplitude decreased with increased gestational age. Additionally, 65% of neonates had a mature sleep-wake cycle in the second week compared with 22% in the first week. The median (interquartile range) CFM score in the second week was 12 (4.5) compared with 8 (4) in the first week, and the CFM score positively correlated with gestation (Spearman correlation coefficient, 0.8; 95% confidence interval, 0.7-0.86). Magalhães grading in both groups was predominantly normal.

Conclusion: aEEG is predominantly a continuous normal voltage pattern in >30 weeks' gestation and discontinuous in ≤30 weeks' gestation. CFM score correlates positively with advancing gestation gestational age.