Brain & Development最新文献

In recent years, the number of diseases included in newborn screening (NBS) tests has increased rapidly, led by the development of both technology and treatments. Many neurometabolic diseases can now be screened, but direct involvement of the brain, especially in the severe forms of these diseases, causes challenges in NBS. For example, differentiating between neuropathic and nonneuropathic types of disease is difficult but critical because the treatments used can differ. For many diseases with neurological manifestations, the long-term outcomes of new treatments and the influence of NBS are both unclear. In this review, we introduce the "new" NBS test using data from the Screening Center at National Taiwan University as an example. Subsequently, we explore the current challenges in NBS for several neurometabolic diseases.

Background: Most cases of spinal muscular atrophy (SMA) can be diagnosed by copy number analysis of survival motor neuron (SMN) 1. However, a small number of cases of SMA can only be diagnosed by sequencing analysis. We present a case of SMA diagnosed 7 years after the onset of symptoms.

Case report: She was a 12-year-old girl of Sri Lankan origin. At age 5, she began to fall easily. She had normal intellectual development, and electromyography suggested a neurogenic disorder. Copy number analysis of SMN1 exons 7 and 8 via polymerase chain reaction revealed at least one copy of SMN1. Exome sequence analysis for neuromuscular disorders panel could not detect the pathogenic mutation. She moved to Japan at the age of 12 years. Sequencing analysis later identified a novel mutation in SMN1 at the same locus as previously reported (c.284G>A: p.Gly95Glu). Multiple ligation-dependent probe amplification indicated she had two copies of SMN2. She was diagnosed with SMA type 3b and treated with nusinersen.

Discussion: In patients with SMA, 2-5 % have a point mutation or a small insertion/deletion in SMN1. Since copy number analysis cannot detect such mutations, sequencing analysis is required. Two copies of SMN2 often result in SMA type 1 or 2, but her mild symptoms of SMA type 3b may be due to a combination of a point mutation and a deletion in SMN1.

Conclusion: Even if genetic testing has been performed at previous institutions, sequencing analysis should be considered if the patient's symptoms are consistent with SMA.

Objective: There are fewer reports on the ictal electroencephalogram(EEG) of convulsions in infants and children with mild gastroenteritis (BCWG). Our study retrospectively analyzed the ictal EEG characteristics of convulsive episodes of BCWG.

Methods: The seizure-phase EEGs of children diagnosed with BCWG from September 2016 to January 2022 were searched and analyzed, and a total of thirteen seizure-phase EEGs of eight cases were analyzed retrospectively.

Results: The age of onset of the disease in the eight children ranged from one year to two years and seven months. No epileptiform discharges were found during the interictal EEG. A total of thirteen epileptic seizures were monitored, of which nine were focal with secondary generalisation. Scalp EEG showed three onset of EEG seizures were in the right occipital region, two were in the right parietal and occipital regions, one was in the right parietal, occipital and posterior temporal region, one was in the right posterior temporal region, one was in the right occipital and posterior temporal region and one was in the right central and central midline region. In addition, four non-convulsive epileptic seizures, which manifested themselves as a decrease in movement and consciousness, with local δ slow-wave activity in bilateral occipital regions evolved to diffuse δ slow wave activity in epileptic seizures.

Conclusion: Focal secondary generalised tonic clonic seizures were the main type of seizures in BCWG, and the seizure onset may been mostly in posterior cephalic cortex. It was previously unreported that some children of BCWG may combine with non-convulsive epileptic seizures with the onset of slow wave activity in the occipital region bilaterally and evolving into diffuse δ slow wave activity, which was not easily detected by parents and clinicians.

Background: Disease-modifying therapies can improve motor function in patients with spinal muscular atrophy (SMA), but efficacy varies between individuals. The aim was to evaluate the efficacy and safety of nusinersen treatment in children with SMA and to investigate prognostic factors.

Methods: Motor function, compound muscle action potential (CMAP), and other indicators were prospectively collected before and 14 months after nusinersen treatment.

Results: A total of 55 children were included in our study to assess safety. 41 patients (with at least 6 months of nusinersen treatment) were included in the final efficacy analyses, with a median age at first treatment of 4.2 years. After 14 months of treatment with nusinersen, motor function improved, with increases in CHOP INTEND (Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders), HINE-2 (Hammersmith Infant Neurological Exam-Part 2), HFMSE (Hammersmith Functional Motor Scale-Expanded) and RULM (Revised Upper Limb Module) of 5.5 (95 % CI -2.4-13.4), 0.8 (95 % CI -0.2-1.9), 5.0 (95 % CI 2.5-7.4) and 2.4 (95 % CI 0.7-4.1) points, respectively. The CMAP amplitudes of the bilateral tibial, median and ulnar nerves increased, with greatest improvements of 0.87 ± 1.41 mV, 1.08 ± 1.71 mV and 0.59 ± 1.01 mV, respectively. Spearman correlation analysis showed that age at first treatment, disease duration, joint contractures and scoliosis were associated with treatment efficacy (r = -0.4-0.7, P < 0.05). Subgroup analyses showed that the mean HFMSE and RULM scores improved in the Physical therapy group (P < 0.05).

Conclusion: Early treatment, mild bone and joint complications, and regular rehabilitation training were associated with better outcomes. The other motor-related functions, such as respiratory and bullar function, and prognostic factors should be studied in the future.

Objective: The present study aimed to investigate the initial clinical features of infantile-onset genetic epilepsy and compare initial seizure variables and responses to sodium channel blockers between SCN1A and non-SCN1A group.

Methods: We selected 122 patients, comprising 58 patients with SCN1A mutations and 64 patients with mutations in other than SCN1A, from our institutional database.

Results: Patients identified in the SCN1A group tended to present with fever, prolonged seizure duration, and hemiclonic seizure semiology. Clustering of seizures was found more frequently in patients from the non-SCN1A group. However, an overlap of seizure variables and seizure type in both groups was also noted. While sodium channel blockers aggravated seizures in more than half of the patients (21/29, 72.4 %) in the SCN1A group, the opposite tendency toward a favorable response to sodium channel blockers (19/30, 63.3 %) was found in those in the non-SCN1A group. Notably, no patient showed seizure aggravation after the use of sodium channel blockers in the non-SCN1A group.

Conclusion: This study highlights the need for comprehensive comparative research to guide the management of infantile onset genetic epilepsy patients.

Introduction: Epileptic encephalopathy (EE) is a serious clinical issue that manifests as part of developmental and epileptic encephalopathy (DEE), particularly in childhood epilepsy. In EE, neurocognitive functions and behavior are impaired by intense epileptiform electroencephalogram (EEG) activity. Hypotheses of pathophysiological mechanisms behind EE are reviewed to contribute to an effective solution for EE.

Review: Current hypotheses are as follows: 1) neuronal dysfunction based on genetic abnormalities that may affect neurocognitive functions and epilepsy separately; 2) impairment of synaptic homeostasis during sleep that may be responsible for DEE/EE with spike-and-wave activation in sleep; 3) abnormal subcortical regulation of the cerebral cortex; 4) abnormal cortical metabolism and hemodynamics with impairment of the neural network including default mode network; 5) neurotransmitter imbalance and disordered neural excitability; 6) the effects of neuroinflammation that may be caused by epileptic seizures and in turn aggravate epileptogenesis; 7) the interaction between physiological and pathological high-frequency EEG activity; etc. The causal relationship between epileptiform EEG activity and neurocognitive dysfunctions is small in DEE based on genetic abnormalities and it is largely unestablished in the other hypothetical mechanisms.

Conclusion: We have not yet found answers to the question of whether the single-central or multiple derangements are present and what seizures and intense epileptiform EEG abnormalities mean in EE. We need to continue our best efforts in both aspects to elucidate the pathophysiological mechanisms of DEE/EE and further develop epilepsy treatment and precision medicine.

Aim: To determine the effect of long-term tobramycin (TOB) inhalation therapy on recurrent pneumonia among ventilator-dependent children with profound neurological disabilities.

Methods: TOB inhalation was performed in eight series of trials in seven ventilator-dependent children who had intratracheal Pseudomonas aeruginosa and suffered from recurrent pneumonia. Their age at the initiation of therapy was 68 ± 50 months (mean ± standard deviation), whereas the duration of treatment was 30 ± 22 months. The participants were followed after the termination of therapy for a period of 38 ± 32 months.

Results: The annual rate of pneumonia was 5.6 episodes per year (n = 8) preceding the initiation of inhalation, which decreased to 3.7 (n = 8), 1.6 (n = 5), and 0.67 (n = 3) in the periods of 0-12, 12-24, and 24-36 months after initiation, respectively. The rates were 1.0 (n = 6), 0.6 (n = 5), and 1.4 (n = 5) in the periods of 0-12, 12-24, and 24-36 months after the termination of therapy.

Interpretation: Extended TOB inhalation therapy was effective in decreasing the morbidity of pneumonia in ventilator-dependent children with severe motor and intellectual disabilities.

Objective: Amplitude-integrated electroencephalogram (aEEG) enables continuous and simplified bedside monitoring of brain function. This review aims to investigate aEEG's value as a predictor of neurodevelopment outcome in preterm infants.

Methods: PubMed, Embase and Web of Science were systematically searched according to the PRISMA in April 2023 and updated in October 2023. The protocol was registered on PROSPERO platform and the methodological quality of studies was analyzed using the Newcastle-Ottawa Scale (NOS).

Results: Nineteen articles (18 cohort and 1 case-control study) were included, reporting the recording of aEEG in 2074 preterm neonates and its association to neurodevelopment outcome. In most studies, aEEG recording started within 72 h of life. The mean NOS score for prospective and retrospective cohort studies were 6 (4-7, median 6) and 6.6 (6-7, median 7), respectively. The case-control study received 7 stars. Burst suppression and low voltage background were associated with poor neurodevelopmental outcome, while normal background and established cyclicity was correlated with a favorable outcome, especially when they occurred in the first week of life.

Conclusion: The background patterns and cyclicity of aEEG seems to be reliable patterns to help predict neurodevelopmental outcome in premature infants, especially when monitorization started early.

Purpose: This study aimed to elucidate the distribution of intracranial gamma-aminobutyric acid (GABA) receptors in patients with infantile epileptic spasms syndrome (IESS) of normal brain MRI findings using ¹²³I-iomazenil single-photon emission computed tomography (IMZ-SPECT).

Methods: This retrospective study compared IMZ-SPECT images from 20 patients with IESS of unknown etiology with normal brain MRI (unknown IESS group) and 23 patients with developmentally normal epilepsy of the same age (developmentally normal group). A three-dimensional stereotactic region of interest (ROI) template was used to divide the brain into 24 segments (left and right callosomarginal, precentral, central, parietal, angular, temporal, posterior cerebral, pericallosal, lenticular nucleus, thalamus, hippocampus, and cerebellum), and the mean accumulation of ¹²³I-iomazenil in each ROI was calculated. The IMZ ratio for each ROI was calculated by dividing the ROI count by the mean cerebellar count of the left and right sides for the same patient. IMZ ratios for 22 ROIs, excluding the cerebellum, between the unknown IESS group and the developmentally normal group were compared.

Results: No significant differences were observed between the background characteristics of the unknown and developmentally normal groups. Hypsarrhythmia were observed in 16 patients in the IESS group. The IMZ ratio showed no significant differences between the two groups across all 22 ROIs.

Conclusion: The IMZ ratio of the unknown IESS group was not significantly different from that of the developmentally normal group across the 22 ROIs, suggesting that GABA receptor distribution has little effect on epileptic spasms and hypsarrhythmia, and vice versa.

Background: Safe pediatric magnetic resonance imaging (MRI) ideally relies on non-sedative techniques, as avoiding risky sedation is inherently safer. However, in practice, sedation often becomes unavoidable, particularly for younger children or those with anxiety, to ensure motion-free, high-quality imaging. This narrative review explores the current practices and proposes strategies to enhance safety in pediatric MRI examinations.

Methods: We identified and analyzed 247 studies addressing various aspects of pediatric MRI safety, including sedation protocols, patient monitoring, and team-based management approaches.

Results: Safe sedation requires careful drug selection tailored to individual needs, continuous monitoring, and robust emergency preparedness. While efforts are underway to minimize sedation, safer drug protocols and improved monitoring technologies remain essential. Assembling dedicated MRI teams trained in both technical and non-technical skills-such as situational awareness, communication, and teamwork-supports these strategies. Structured team briefings covering monitoring procedures, emergency scenarios, response protocols, and specific resuscitation roles are also critical. Developing a strong organizational culture that promotes patient safety and continuous learning from incident reports helps ensure ongoing improvements.

Conclusions: Achieving safe pediatric MRI examinations requires balancing the need for sedation with the goal of minimizing its use. Strengthening collaboration, refining sedation protocols, and implementing advanced safety monitoring systems are essential steps. Further advancements in imaging technologies are also necessary to reliably obtain high-quality scans without sedation, reducing risks and improving patient outcomes.