Neuropediatrics最新文献

We comment on a recent report proposing epileptic spasms as the predominant motor manifestation in subacute sclerosing panencephalitis (SSPE). Based on detailed video-EEG and polygraphic analysis, we argue that the described motor events differ fundamentally from epileptic spasms and are better interpreted as complex paroxysmal motor phenomena related to periodic EEG complexes. Accurate phenomenological and neurophysiological classification is essential to avoid diagnostic ambiguity in SSPE.

Hemiconvulsion-hemiplegia-epilepsy (HHE) syndrome is a rare pediatric epilepsy syndrome characterized by prolonged focal febrile seizures, postictal hemiparesis, and progressive unilateral brain injury, often followed by chronic epilepsy. We report a previously healthy 10-month-old girl who presented with a prolonged left-sided focal fever-associated seizure. She tested positive for SARS-CoV-2 but did not meet criteria for multisystem inflammatory syndrome in children. On admission, she had left-sided flaccid hemiparesis. Brain MRI showed mild diffusion restriction and marked hyperperfusion of the right hemispheric gray matter, most prominently in the frontal, temporo-occipital, and hippocampal regions. EEG showed high-amplitude slowing over the right hemisphere without epileptiform discharges. No further seizures occurred, and long-term antiseizure treatment was not required. At 9-month follow-up, the patient was seizure-free and developmentally age-appropriate, but the hemiparesis persisted. Serial MRI showed progressive right hemispheric cortical and subcortical atrophy and hippocampal sclerosis. Extensive diagnostic workup found no other structural, infectious, or metabolic cause. This case illustrates the classical biphasic course of HHE syndrome and highlights the diagnostic value of early MRI, EEG, and genetic testing. The patient carried a paternally inherited heterozygous IRF3 variant, a gene essential for innate antiviral immunity. Although causality cannot be established, the temporal association with SARS-CoV-2 infection and an IRF3 variant suggests a possible genetic predisposition to infection-triggered injury. Continued clinical vigilance and long-term follow-up are essential, as epilepsy develops in most children with HHE. Greater awareness of this syndrome may support earlier recognition and timely rehabilitation to optimize functional outcomes.

Two adolescent female patients, who were referred independently of each other, presented with progressive gait disturbances that worsened over the course of the day. Symptoms began in early childhood with foot instability and progressed to clubfoot, pain, and limping. MRI of the neuroaxis did not reveal any central nervous system abnormalities. Genetic testing identified the same intronic variant of uncertain significance in GCH1 in both individuals. Subsequent investigations uncovered a previously unrecognized familial relationship between the two patients, belonging to an extended family in which six women were affected by a gait disorder. Previous diagnoses within the family included childhood-onset spasticity and psoriatic arthritis. The familial GCH1 variant was confirmed in all symptomatic individuals, as well as in two asymptomatic female carriers. RNA sequencing revealed a splicing defect caused by the GCH1 near splice-site variant. A robust clinical response to L-DOPA therapy confirmed the diagnosis of DOPA-responsive dystonia (DRD) in this family. This case highlights the phenotypic variability of DRD, which frequently leads to misdiagnosis and delays in appropriate treatment. Careful assessment of family history and recognition of diurnal symptom fluctuations are key to identifying this highly treatable condition.

The timing and indications for endoscopic third ventriculostomy (ETV) in pediatric hydrocephalus are debated. We evaluated head circumference growth as a predictor of ETV success in children with posthemorrhagic hydrocephalus (PHH).We conducted a retrospective review of 303 patients who underwent ETV from 2012 to 2021, focusing on those with intraventricular hemorrhage (IVH) and PHH. Data were collected from electronic medical records. A univariate logistic regression analyzed predictors of ETV failure, with head circumference growth rate calculated from preoperative occipito-frontal circumference measurements.Among the 303 patients, 24 had IVH and PHH. Mean gestational age was 30 weeks, with 58% male, and a mean weight of 4.48 kg at surgery. Notably, 96% (n = 23) had choroid plexus cauterization, and 46% (n = 11) underwent ventriculosubgaleal shunt. Of the 24, 67% (n = 16) required eventual ventriculoperitoneal shunt (VPS) placement, indicating ETV failure. Corrected age at ETV was younger in the failure group (0.69 months) than in the success group (2.56 months, p = 0.020, odds ratio [OR]: 1.04). Mean weight at surgery was lower for the failure group (3.85 kg vs. 5.75 kg, p = 0.036). Duration of preoperative surveillance was 1.94 months for the failure group and 5.25 months for the success group (p = 0.004). Head circumference growth rate was 1.57 mm/day in the failure group compared to 0.85 mm/day in the success group (p = 0.009, OR: 39.9).Younger corrected age, lower weight at surgery, shorter preoperative surveillance time, and faster head circumference growth rate were associated with ETV failure and ultimately VPS placement. Further analysis with a larger cohort may enhance predictions of ETV success rates.

Epilepsy significantly impacts the health-related quality of life (HRQoL) of children and adolescents (CaA). This study aimed to assess HRQoL in pediatric epilepsy patients compared to their healthy peers, using both self- and proxy-reports, and to identify specific HRQoL domains affected by epilepsy.A single-center, cross-sectional study was conducted in Munich between October 2021 and June 2023. HRQoL was assessed in 139 patients aged 3 to 17 years with medically diagnosed epilepsy using age-adapted, validated KINDL© questionnaires, completed by the patients and one caregiver. The questionnaire comprised six subscales: "Physical Well-being," "Emotional Well-being," "Self-Esteem," "Family," "Friends," and "Everyday Functioning." Control values from healthy CaA aged 7 to 17 were drawn from the BELLA and KiGGS studies. Welch tests and Wilcoxon signed-rank tests were used for statistical comparisons.Compared to their healthy peers, CaA with epilepsy reported significantly lower HRQoL overall, particularly in the subscales "Physical Well-being," "Emotional Well-being," and "Friends." No significant differences were observed in the "Family" subscale. Interestingly, self-reports revealed a trend toward higher "Self-Esteem" scores among CaA with epilepsy, though this did not reach statistical significance. No significant differences emerged between self- and proxy-reported total HRQoL scores.Epilepsy in CaA is associated with reduced HRQoL, especially in physical, emotional, and social domains. Stable family support can cushion some negative effects. In particular, the unexpectedly high results in the area of self-confidence should be the subject of future research.

The congenital disorders of glycosylation (CDG) encompass >190 multiorgan disorders with predominantly neurodevelopmental phenotypes with no causative treatment available. The glycoprotein biotinidase (BTD) provides biotin, an essential cofactor for carboxylases in ubiquitous metabolic pathways. Individuals with (partial) BTD deficiency (BTDD) and CDG patients show overlapping phenotypes like movement disorders, seizures, and neurodevelopmental issues. Biotin is a water-soluble, inexpensive, and safe food supplement. Patients with primary BTDD respond well to oral biotin supplement. We here explore secondary BTDD and the effect of biotin supplementation in PMM2-CDG in an initial open-label study.BTD activity in dried blood spots from 29 individuals with PMM2-CDG indicated a mean reduction to 27% (range: 23.0-40.5%) at group level. Patients (mean: 19.6 ± 11.9 years) were supplemented with 10 mg biotin daily for 12 months. The parents/caretaker reported positive responses in 62 to 69% of patients across seven (performance, social, at home, self-control, self-care, leisure, health) of the nine categories covered by the Adaptive Behavior Assessment System-II (ABAS-II) questionnaires. The reported positive effect of biotin supplementation differed between age groups, ranging from 54% (16-43 years) via 62% (2-5 years) to 80% (6-13 years). Its effect was reported to be the highest in the moderate to severely affected patient subgroups, with significant improvements in home functioning, health, performance, leisure, self-control. No adverse effects were reported.Given the absence of other treatments, the supportive effect of Biotin in PMM2-CDG deserves further exploration.

Prevalence of seizures is 1 to 5/1,000 neonates. The most common causes of neonatal seizures are hypoxic-ischemic encephalopathy (HIE), vascular events (hemorrhages, stroke), and infections. We assessed prevalence and etiology of seizures defined according to the recent Brighton and International League of Epilepsy (ILAE) criteria in a neonatology monocenter cohort.In a retrospective cross-sectional cohort study of all 12,154 neonates born in our three maternities from January 1, 2022 to December 31, 2023 seizures were categorized by frequency, etiology, risk profile, semiology, and EEG. A total of 19 neonates (male: n = 11 [57.9%]; full-term: n = 11 [57.9%]; preterm very low birth weight [VLBW]: n = 6 [31.6%]; preterm >1,500 g birth weight: n = 2 [10.5%]) were identified.In 19/12,154 neonates, seizures were confirmed by application of the ILAE criteria. Preterm VLBW was found in 174 neonates with birth weight <1,500 g. Seizure incidence was 1.6/1,000 in all neonates and 3.4% in VLBW infants. HIE was the most frequent etiology in term infants (30.8%), followed by vascular events in preterm >1,500 g and term infants (30.8%). Vascular events were the most common cause in preterm VLBW infants (83.3%). Whole exome sequencing (WES) was performed in four cases (21.1% of neonates with seizures).Incidence of neonatal seizures in our center is in the lower range and leading seizure etiologies are comparable to the literature. Early recognition of neonatal seizures including the detection of electrographic-only seizures and early WES to identify rare genetic defects possibly offering tailored treatment options have the potential to further raise the standard of neonatal care and improve neurodevelopmental outcome.