Annals of the Child Neurology Society最新文献

Objective

This study identified biomarkers of neurological outcome in Sturge-Weber syndrome (SWS) via urine angiogenic factors and captured longitudinally derived natural history data within an SWS cohort.

Methods

This longitudinal, prospective, multicentered study of 61 people with SWS aged 0.4–55 years reports port-wine birthmark score, Neuroscore, Neuro-Quality of Life, and urine angiogenic factors over a two-year period.

Results

Cognitive Neuroscore worsened over time for children aged 0–2 years. Male sex was associated with worsening Cognitive Function Neuroscore during the study. Age of seizure onset before 2 years was strongly associated with worse Neuroscore. Children with SWS had low Neuro-Quality of Life related to cognitive function. Seizure severity, male sex, and earlier age of seizure onset were associated with worse Neuro-Quality of Life in school-aged children. Children with SWS have elevated basic fibroblast growth factor in their urine compared with controls, whereas higher vascular endothelial growth factor was associated with better Neuroscore.

Interpretation

This study is the first multicenter, prospective, and longitudinal study of people with SWS. It identifies significant clinical prognostic factors such as age of seizure onset and male sex, informs symptom progression over time by age group, and suggests that further study of angiogenic mechanisms and potential biomarkers are needed.

Objectives

Migraine is a prevalent neurological disorder severely impacting children and adolescents, yet only one pharmacological treatment is approved for ages 6−12 years. Remote electrical neuromodulation (REN) is a nonpharmacological, prescribed, wearable device cleared by the Food and Drug Administration for acute and/or preventive treatment of migraine with or without aura in patients 12 years and older. This study evaluates REN's safety and efficacy in ages 6−11 years.

Methods

Prospective acute treatment of migraine data were collected through the REN device (Nerivio) smartphone application. Endpoints were device safety (primary); consistent treatment efficacy (headache pain, functional disability, associated migraine symptoms), and REN-medication combinations 2 h post-treatment.

Results

Children (n = 293), median age 11 years (interquartile range = 9−11), 73.7% girls, conducted 5493 REN treatments. No adverse events were reported. Efficacy in at least 50% of REN treatments was calculated from all patients who voluntarily reported pain levels, symptoms, and/or disability at treatment onset and at 2 h post-treatment, with 72.2% (13/18) of patients reporting pain relief, 36.0% (9/25) pain freedom, 83.3% (15/18) functional disability relief, and 38.9% (7/18) functional disability freedom. Migraine-associated symptoms disappeared in at least 50% of REN treatments in 70.0% (7/10) of patients for nausea/vomiting, 50.0% (4/8) phonophobia, and 22.2% (2/9) photophobia; 63.6% (7/11) reported freedom from at least one associated symptom. REN was used as a standalone treatment, with over-the-counter medications, and with prescribed headache medications in 45.4%, 34.4%, and 20.9% of treatments, respectively.

Interpretation

REN may serve as a safe and efficacious acute treatment of migraine for children. Providers and families seeking a safe, effective, pill- and needle-free treatment option for children suffering from migraine may consider REN.

Objective

This study assessed anxiety levels in children during the COVID-19 pandemic and explored how factors related to COVID-19 may have affected the prevalence of anxiety disorders among the pediatric population.

Methods

Childhood anxiety symptoms were assessed at various pediatric practices in Central New Jersey between July 2021 and September 2022. The sample comprised 476 children and adolescents aged 8–17 who participated in the Screen for Child Anxiety Related Disorders (SCARED) questionnaire, administered at their annual well-child visits. Participants included both the child and the caregiver. The anxiety prevalence was compared with prepandemic standards published by the Centers for Disease Control (CDC).

Results

The prevalence of anxiety for children aged 8–17 years (28.3%) was greater than prepandemic levels (7.1%; p < 0.0001). Among children aged 8–11, anxiety increased from 6.6% to 38.1% (p < 0.0001), while for children aged 11–17, anxiety increased from 10.5% to 22.2% (p < 0.0001). Previously diagnosed anxiety was a strong predictor of a high anxiety score on the questionnaire (mean = 28.95) compared with children without a history of anxiety (mean = 17.65; p < 0.001). Furthermore, a disparity was identified in the responses between the child and the caregiver questionnaires (p < 0.0001).

Conclusion

This study shows that children's anxiety levels increased during the COVID-19 pandemic. Moreover, an inconsistency was found between children self-reporting anxiety and caregivers underreporting their child's anxiety. These findings underscore the need for targeted support for those affected, especially children with a history of anxiety.

Objective

Tuberous sclerosis complex (TSC) results from overactivity of the mechanistic target of rapamycin (mTOR). Sirolimus and everolimus are mTOR inhibitors that treat most facets of TSC but are understudied in infants. We sought to understand the safety and potential efficacy of preventative sirolimus in infants with TSC.

Methods

We conducted a phase 1 clinical trial of sirolimus, treating five patients until 12 months of age. Enrolled infants had to be younger than 6 months of age with no history of seizures and no clinical indication for sirolimus treatment. Adverse events (AEs), tolerability, and blood concentrations of sirolimus measured by tandem mass spectrometry were tracked through 12 months of age, and clinical outcomes (seizure characteristics and developmental profiles) were tracked through 24 months of age.

Results

There were 92 AEs, with 34 possibly, probably, or definitely related to treatment. Of those, only two were grade 3 (both elevated lipids) and all AEs were resolved by the age of 24 months. During the trial, 94% of blood sirolimus trough levels were in the target range (5–15 ng/mL). Treatment was well tolerated, with less than 8% of doses held because of an AE (241 of 2941). Of the five patients, three developed seizures (but were well controlled on medications) at 24 months of age. Of the five patients, four had normal cognitive development for age. One was diagnosed with possible autism spectrum disorder.

Interpretation

These results suggest that sirolimus is both safe and well tolerated by infants with TSC in the first year of life. Additionally, the preliminary work suggests a favorable efficacy profile compared with previous TSC cohorts not exposed to early sirolimus treatment. Results support sirolimus being studied as preventive treatment in TSC, which is now underway in a prospective phase 2 clinical trial (TSC-STEPS).

Background

Sudden unexpected death in epilepsy (SUDEP) is the most common cause of epilepsy-related mortality. Although most witnessed SUDEPs follow seizures, mechanisms are uncertain. Investigations into the pathophysiology of SUDEP have relied on models and rare recordings of brain function at the time of the event. The brain-responsive neurostimulation (RNS) device from Neuropace offers a therapeutic option for drug-refractory epilepsy (DRE), enabling the recording of brain activity and the preemptive termination of seizures. Therefore, patients who experience SUDEP while being treated with an RNS device can provide insights into neural activity at the moment of this event.

Objective

We report the history and electrocorticographic (ECoG) recordings of a patient with DRE who experienced SUDEP years after RNS placement.

Patient History

A girl with Phelan–McDermid syndrome and Lennox–Gastaut syndrome had an RNS device implanted at the age of 14 to treat DRE. Initially, electrodes were positioned in the right orbitofrontal (OF) and right premotor frontal regions, with the OF lead later changed to the centromedian thalamic nucleus. At age 19, the patient was found unconscious and in cardiac arrest by her parents. Although spontaneous circulation returned en route to the hospital, the patient did not regain consciousness and died. Subsequent analysis of ECoGs from RNS recordings at the time of death indicated seizure onset in the right premotor frontal cortex, which persisted despite seizure termination attempts by the RNS.

Conclusions

We present a patient with SUDEP associated with the onset of RNS-refractory seizures. The significance of this report is highlighted by the rarity of literature on neuronal function at the time of SUDEP. Moreover, it underscores the potential for devices capable of monitoring ECoG activity to shed light on the mechanisms underlying SUDEP and to inform interventions.

Objective

Dravet syndrome (DS) is an epileptic encephalopathy caused by haploinsufficiency of the SCN1A gene. SCN1A gene deficiency limits the firing rates of fast-spiking inhibitory interneurons, which should reflect in abnormal aggregate network oscillatory electroencephalography (EEG) activity that can be measured by spectral power and phase-amplitude coupling (PAC) analysis. In this retrospective pilot study, we tested whether spectral EEG frequency band power and PAC metrics distinguish children with DS from age-matched controls, an early step toward establishing EEG markers of target engagement by gene or drug therapy.

Methods

EEG data were collected from patients with DS (N = 6) and age-matched control pediatric participants (N = 11) and analyzed for cumulative spectral power and PAC and classification capacity of these metrics, by logistic regression analysis. For this initial spectral and PAC analysis, we focused on sleep EEG, where myogenic artifact is minimal and where δ–γ and θ–γ coupling is otherwise expected to be robust.

Results

Cumulative δ (1– <4 Hz) and θ (4–7 Hz) power was significantly reduced in the DS group, compared with age-matched controls (p = 0.001 and p = 0.02, respectively). The δ power was a stronger classifier of separating DS from controls than θ power, with 87% and 83% accuracy, respectively. The γ power trended toward significant reduction (p = 0.08) in the DS group. We found significantly lower PAC between 1–2 Hz phase and 63–80 Hz amplitude in patients with DS compared with the age-matched controls (p = 0.003), with 78% classification accuracy between groups for PAC.

Interpretation

In this pilot study assessing EEG patterns during sleep, we found lower δ–θ power and PAC in patients with DS versus controls, which may reflect abnormal aggregate macroscale network communication patterns resulting from SCN1A deficiency. These measures may be useful metrics of therapeutic target engagement, particularly if the therapy restores the underlying DS pathophysiology. The sorting capacity of these metrics distinguished patients with DS from patients without DS and may in turn facilitate near-future development of disease and therapy target engagement biomarkers in this syndrome.

The neurology of creativity implies network activity; no singular cerebral area is invoked. A clinician-scientist can develop a creative research project from a single patient, combined with critical scientific alliances, careful observations, and correlations. The developing nervous system poses additional complexity, as changes are expected over time in physiologic circumstances, to which must be added compensatory responses to underlying pathology. The arts represent an especially productive area to study the neurology of creativity, especially with functional imaging, tractography, and intracranial electrophysiology. Music activates widespread bilateral areas, including temporal, orbitofrontal, insular, fusiform, and cerebellar cortex. There are different neuronal clusters for different levels of sound volume, duration, timbre, and pitch. Heschl's gyrus and the arcuate fasciculus correlate with pitch. The orbitofrontal cortex is involved in expectancy generation and appears to be active with no music and then deactivates with music, as if the cortex has an editing function. This appears to correlate with the default mode network being key during improvisation, whereas the central executive network is invoked in effortful, repetitive playing. Furthermore, plasticity is associated with music, from the pathologic development of musicogenic seizures, to protection from musician's dystonia in pianists who begin lessons before age 9 years, to benefits of increased temporal cortex in older adults taking piano lessons after six months. Creativity, reducing negativity bias, and juggling life s priorities are key to countering burnout and building resilience.