Haemodynamic Responses to Spontaneous Neural Activity on the Electroencephalogram in Preterm Infants.

Delta brushes are spontaneous neural activities observed in preterm electroencephalograms (EEGs) and are thought to reflect the activities of subplate neurons in the developing brain. We investigated the haemodynamic responses associated with delta brushes in five preterm infants at two time points (at 33 or 34, and 36 weeks of postmenstrual age), using simultaneous EEG-functional near-infrared spectroscopy (NIRS). An automated detection algorithm was developed to identify the brush components of delta brushes in the bipolar EEG envelope; we placed eight EEG electrodes. An eight-channel NIRS device was placed around the head of each infant to measure changes in oxy- and deoxy-haemoglobin (Hb) concentrations. Haemodynamic grand averages were calculated for local brushes in each NIRS channel. We classified the responses into five patterns based on changes in oxy- and deoxy-Hb signals (positive in-phase/anti-phase, negative in-phase/anti-phase, and unclassified) and evaluated the relationship between the locations of NIRS measurements and those of brushes, as well as the haemodynamic response patterns and infant age at the time of recording. In all the 10 recordings, we found that positive responses (oxy-Hb increases) predominated, not only in the corresponding areas but also in remote areas. Particularly, notable responses were observed in the bilateral temporal areas. Among the positive responses, the proportion exhibiting an anti-phase pattern was 12% at 33 to 34 weeks of postmenstrual age and 54% at 36 weeks of postmenstrual age. Our unexpected finding of remarkable temporal responses to localised neuronal activity supports the hypothesis that the insula is the most strongly interconnected hub in the developing brain.

Sleep state-dependent development of resting state functional connectivity during the preterm period.

STUDY OBJECTIVES: The brains of preterm infants exhibit altered functional connectivity (FC) networks, but the potential variation in sleep states and the impact of breathing patterns on FC networks are unclear. This study explores the evolution of resting-state FC from preterm to term, focusing on breathing patterns and distinguishing between active sleep and quiet sleep. METHODS: We recruited 63 preterm infants and 44 healthy-term infants and performed simultaneous electroencephalography and functional near-infrared spectroscopy. FC was calculated using oxy- and deoxyhemoglobin signals across eight channels. First, FC was compared between periodic breathing (PB) and non-PB segments. Then sleep state-dependent FC development was explored. FC was compared between active sleep and quiet sleep segments and between preterm infants at term and term-born infants in each sleep state. Finally, associations between FC at term, clinical characteristics, and neurodevelopmental outcomes in late infancy were assessed in preterm infants. RESULTS: In total, 148 records from preterm infants and 44 from term-born infants were analyzed. PB inflated FC values. After excluding PB segments, FC was found to be elevated during active sleep compared to quiet sleep, particularly in connections involving occipital regions. Preterm infants had significantly higher FC in both sleep states compared to term-born infants. Furthermore, stronger FC in specific connections during active sleep at term was associated with unfavorable neurodevelopment in preterm infants. CONCLUSIONS: Sleep states play a critical role in FC development and preterm infants show observable changes in FC.

Clinical Practice Guidelines for the Management of Congenital Cytomegalovirus Infection in Japan 2023: Executive Summary.

Congenital cytomegalovirus (cCMV) infection is the most common congenital infection in developed countries. Although a standard therapy has not yet been established, evidence for the management of cCMV infection has been accumulating. The first edition of the "Clinical Practice Guidelines for the Management of Congenital Cytomegalovirus Infection" was published in Japan in 2023. This summary outlines the clinical questions (CQs) in the guidelines, with reference to the Japanese Medical Information Distribution Service Manual. Overall, 20 CQs with statements regarding prenatal risk assessment, prevention and management at diagnosis (CQs 1-1-1-3), diagnosis (CQs 2-1-2-6), treatment (CQs 3-1-3-7) and follow-up requirements (CQs 4-1-4-4) have been discussed. For each statement, the levels of recommendation, evidence and consensus rates were determined. These guidelines will assist in the management of patients with cCMV infection.

Underlying Disorders in Children With Infection-Related Acute Encephalopathy.

BACKGROUND: Various factors contribute to the development of infection-related acute encephalopathy (AE) in children, such as infectious agents and chronic underlying disorders. We studied underlying disorders in children with AE to identify predisposing factors of AE. METHODS: We investigated underlying disorders or past histories in patients with two types of AE from the database in the Tokai area of Japan between 2009 and 2022: 204 patients with AE with reduced subcortical diffusion (AED) and 137 with clinically mild encephalopathy with a reversible splenial lesion (MERS). We compared them with 89 patients with acute disseminated encephalomyelitis (ADEM) to clarify the specific disorders in the two AE types. RESULTS: The prevalence of underlying disorders in AED (34%, 70 patients) was significantly higher than that in ADEM (12%, 11 patients) (P < 0.01). The prevalence of underlying disorders in MERS was 23% (32 patients). The underlying disorders included seizure disorders, premature birth, genetic/congenital disorders, and endocrine/renal diseases. In patients with seizure disorders in AED, five patients (18%) had Dravet syndrome and four (15%) had West syndrome, whereas none with MERS had these syndromes. Twenty-five (12%) of 204 patients with AED, three (2%) with MERS, and one (1%) with ADEM were preterm or low birth weight. CONCLUSIONS: The high prevalence of seizure disorders suggests that seizure susceptibility is an important predisposing factor in AED. Premature birth also has an impact on the development of AED. Caution is required regarding the development of AE in patients with chronic seizure disorders or premature birth.

Three-Dimensional Gait Analysis as a Biomarker for GTP Cyclohydrolase 1-Deficient Dopa-Responsive Dystonia.

BACKGROUND: GTP-cyclohydrolase 1-deficient dopa-responsive dystonia (GTPCH1-deficient DRD) typically presents in childhood with dystonic posture of the lower extremities, gait impairment, and a significant response to levodopa. We performed three-dimensional gait analysis (3DGA) to quantitatively assess the gait characteristics and changes associated with levodopa treatment in patients with GTPCH1-deficient DRD. METHODS: Three levodopa-treated patients with GTPCH1-deficient DRD underwent 3DGA twice, longitudinally. Changes were evaluated for cadence; gait speed; step length; gait deviation index; kinematic data of the pelvis, hip, knee, and ankle joints; and foot progression angle. RESULTS: Levodopa treatment increased the cadence and gait speed in one of three patients and increased the gait deviation index in two of three patients. The kinematic data for each joint exhibited different characteristics, with some improvement observed in each of the three patients. There was consistent marked improvement in the abnormal foot progression angle; one patient had excessive external rotation of one foot, another had excessive bilateral internal rotation, and the other had excessive internal rotation of one foot and excessive external rotation of the opposite foot, all of which improved. CONCLUSION: The 3DGA findings demonstrate that the gait pathology and recovery process in GTPCH1-deficient DRD vary from case to case. Changes in the foot progression angle and gait deviation index can enable the effects of treatment to be more easily evaluated.

The eldest case of MICPCH with CASK mutation exhibiting gross motor regression.

BACKGROUND: MICPCH is manifested as microcephaly associated with pontocerebellar hypoplasia and global developmental delay but developmental regression has never been reported. We describe the detailed clinical history of a woman with intellectual disability and microcephaly with pontine and cerebellar hypoplasia (MICPCH) with a CASK mutation who exhibited gross motor regression after adolescence. CASE: The patient experienced severe motor and intellectual developmental delay with microcephaly from infancy. The initial diagnosis was Rett syndrome based on her clinical features, including hand stereotypes and the absence of structural abnormality on magnetic resonance imaging (MRI) performed at the age of 5 years. Although gross motor abilities developed slowly and she could walk independently, she never acquired speech or understanding of languages. After adolescence, her motor ability gradually regressed so that she was unable to stand without support and moved with a wheelchair. At the age of 31 years, because of her atypical clinical course for Rett syndrome, whole exome sequencing was performed, which revealed a de novo heterozygous c.2068 + 1G > A mutation in the CASK gene (NM_001126055). Brain MRI revealed mild pontocerebellar hypoplasia compatible with the clinical phenotype of MICPCH. DISCUSSION: This case suggests that MICPCH with a CASK mutation might cause developmental regression after adolescence and might be regarded as a neurodegenerative disorder.