Brain & Development最新文献

Aim

To clarify the relationship between early infantile spontaneous movement of very-low-birth-weight infants (VLBWIs) and sensory characteristics in childhood.

Study design

Prospective cohort study. We investigated the association between the Motor Optimality Score-Revised (MOS-R), a detailed assessment of general movements (GMs) at the corrected age of 9–17 weeks and the Infant/Toddler Sensory Profile Japanese version (ITSP-J) at the corrected age of 3 years. A multiple regression analysis was performed to examine the correlation of ITSP-J and MOS-R with patient clinical background factors.

Subjects

Fifty-three VLBWIs (median gestational age: 28 weeks, 6 days; median birth weight: 997 g) who were managed at the NICU of Oita University from September 2013 to June 2019.

Results

A multiple regression analysis revealed that the ITSP-J subscale in the sensory section of visual score was significantly correlated with the age-adequate movement repertoire subscore of MOS-R, and in the sensory section of vestibular score was correlated with the fidgety subscore of MOS-R. For both visual and vestibular section scores, intraventricular hemorrhage (IVH) showed an independent association with the MOS-R subscore.

Conclusion

Spontaneous movement characteristics in early infancy were associated with sensory characteristics in early childhood.

Background

MECP2 is a well-known causative gene for Rett syndrome but other phenotypes have also been reported. Here, we report a case of a female patient with adolescent-onset progressive myoclonus epilepsy (PME) carrying a novel truncating mutation in the MECP2 gene.

Case report

The patient was a 29-year-old woman with infantile-onset intellectual disability of unspecified cause. She had demonstrated slow but steady development with moderate intellectual disability until the age of 16, when she started having epileptic seizures. Her epilepsy progressed intractably with multiple seizure types accompanied by myoclonus, tremor, and gradual regression. She is currently apathetic and requires extensive assistance in all aspects of life. After an extensive work-up for underlying diseases for PME turned out negative, whole-exome sequencing revealed a de novo 113-bp deletion and 3-bp insertion in MECP2, a variant of NM_004992.4:c.1099_1211delinsGGG, p.(His367Glyfs*32).

Conclusions

The clinical presentation of this case was inconsistent with Rett syndrome, and the rapid regression in the patient’s twenties was considered characteristic. Mutations of MECP2 may result in variable neurodevelopmental phenotypes and may also be considered a causative gene for adolescent-onset PME.

Neonatal hypoxic-ischemic encephalopathy (HIE) is a common disease among newborns, which is a leading cause of neonatal death and permanent neurological sequelae. Therapeutic hypothermia (TH) is the only method for the treatment of HIE that has been recognized effective clinically at home and abroad, but the efficacy is limited. Recent research suggests that the cord blood-derived mononuclear cells (CB-MNCs), which the refer to blood cells containing one nucleus in the cord blood, exert anti-oxidative, anti-inflammatory, anti-apoptotic effects and play a neuroprotective role in HIE. This review focuses on safety and efficacy, the route of administration, dose, timing and combination treatment of CB-MNCs in HIE.

Background

ATP6V1B2 (ATPase, H+ transporting, lysosomal VI subunit B, isoform 2) encodes for a subunit of a ubiquitous transmembrane lysosomal proton pump, implicated in the acidification of intracellular organelles and in several additional cellular functions. Variants in ATP6V1B2 have been related to a heterogeneous group of multisystemic disorders sometimes associated with variable neurological involvement. However, our knowledge of genotype-phenotype correlations and the neurological spectrum of ATP6V1B2-related disorders remain limited due to the few numbers of reported cases.

Case study

We hereby report the case of an 18-year-old male Sicilian patient affected by a global developmental delay, skeletal abnormalities, and epileptic encephalopathy featuring Lennox-Gastaut syndrome (LGS), in which exome sequencing led to the identification of a novel de novo variant in ATP6V1B2 (NM_001693.4: c.973G > C, p.Gly325Arg).

Conclusions

Our report provides new insights on the inclusion of developmental epileptic encephalopathies (DEEs) within the continuum group of ATP6V1B2-related disorders, expanding the phenotypic and molecular spectrum associated with these conditions.

Purpose

Patients with periventricular leukomalacia (PVL) have been reported to have a variety of complications; however, whether these involve impaired visual attention disabilities remains unclear. Therefore, this study aimed to investigate the presence or absence and degree of visual attention disabilities in patients with PVL and propose a screening test that would allow anyone to check for visual attention disabilities easily.

Methods

The study participants were 14 patients with PVL and seven controls with dyskinetic cerebral palsy. All participants performed three types of visual attention tasks: spatial attention tasks, feature-based attention tasks, and object-based attention tasks. The participants also performed counting tasks to determine how many squares of the same size and color could be counted (up to nine). Receiver operating characteristic analysis was used to calculate cutoff values, with disability as the objective variable and the value of the counting task as the explanatory variable.

Results

The results revealed that patients with PVL often had visual attention disabilities, as indicated by a significant reduction in tasks requiring divided attention. Visual attention disabilities could be detected by a score of ≤8 in the square counting task.

Conclusions

These findings suggest that family members and teachers of patients with PVL can easily screen for visual attention disabilities at home and school to improve mobility precautions in patients with this disability.

Introduction

Since the emergence of COVID-19, we have experienced potent variants and sub-variants of the virus with non-specific neurological manifestations. We observed a surge of the Omicron variant of COVID-19 patients with neurological manifestations where less cases of multisystem inflammatory syndrome in children (MIS-C) were reported. This article describes our experience of children with severe and rare neurological manifestations following COVID-19 infection.

Methods

This is a retrospective observational case series of patients under 18 years old who fulfilled the WHO COVID-19 case definition and were referred to our paediatric neurology unit at Hospital Tunku Azizah Kuala Lumpur. Their demographic data, neurological symptoms, laboratory and supporting investigations, neuroimaging, treatment and outcomes were collected and analysed.

Results

There were eleven patients with neurological manifestations who fulfilled the WHO COVID-19 case definition. Nine patients presented with seizures and/or encephalopathy, one patient with eye opsoclonus and another patient with persistent limbs myokymia. Based on the history, clinical, electrophysiological and radiological findings, two of them had febrile infection-related epilepsy syndrome, two had acute disseminated encephalomyelitis, two had acute necrotising encephalopathy of childhood, one each had hemiconvulsion-hemiplegia-epilepsy syndrome, acute encephalopathy with bilateral striatal necrosis, hemi-acute encephalopathy with biphasic seizures and reduced diffusion, infection-associated opsoclonus and myokymia.

Conclusions

This case series highlighted a wide spectrum of neurological manifestations of COVID-19 infection. Early recognition and prompt investigations are important to provide appropriate interventions. It is essential that these investigations should take place in a timely fashion and COVID-19 quarantine period should not hinder the confirmation of various presenting clinical syndromes.

Background

Encephalomyeloradiculoneuropathy (EMRN) is characterized by progressive neurological symptoms in the central and peripheral nervous systems. The autoantibodies against neutral sphingolipids are disease-specific antibodies against EMRN. Although adults with EMRN typically present with symptoms of peripheral nervous system involvement, the symptoms in pediatric patients are not well understood.

Case

A 4-year-old boy was admitted to our hospital on the 10th day of fever due to poor oral intake and hyponatremia. The day after admission, he developed seizures and impaired consciousness and was transferred to our hospital. When he arrived at our hospital, he experienced disturbances in consciousness, neck rigidity, and opisthotonus. MRI of the head revealed scattered white matter lesions and pleocytosis in the cerebrospinal fluid (CSF). During treatment with intravenous methylprednisolone (IVMP), the patient developed diminished deep tendon reflexes in the lower extremities four days later, with no improvement in cervical stiffness or opisthotonos. Additional evaluations revealed enlarged cerebral white matter lesions on brain MRI, cauda equina enhancement on MRI of the spinal cord, axonal neuropathy in the bilateral tibial nerves, and positive anti-neutral glycosphingolipid (GSL) antibodies in both serum and CSF. Intensive immunomodulatory therapy, and neurorehabilitation, led to substantial neurological recovery within three months of onset.

Conclusion

Pediatric antineutral GSL antibody-positive EMRN may initially present with extensive cerebral white matter lesions and delayed onset of peripheral radiculoneuropathy. Our case extends the disease spectrum of EMRN and may aid in the early diagnosis of EMRN in the pediatric population.

Background

Mutations in the FBXO28 gene, which encodes FBXO28, one of the F-box protein family, may cause developmental and epileptic encephalopathy (DEE). FBXO28-related DEE is radiologically characterized by cerebral atrophy, delayed/abnormal myelination, and brain malformation; however, no neurochemical analyses have been reported.

Case report: A female Japanese infant presented with severe psychomotor delay, epileptic spasms, and visual impairment. Whole-exome sequencing revealed a de novo variant of the FBXO28 gene, leading to the diagnosis of FBXO28-related DEE. Magnetic resonance (MR) spectroscopy at 6, 12, and 32 months revealed decreased N-acetylaspartate and choline-containing compounds and increased levels of myoinositol.

Conclusion

MR spectroscopy revealed neurochemical derangement in FBXO28-related DEE, that is, disturbed myelination secondary to neuronal damage with astrogliosis.

Background

This study aimed to evaluate the neurofilament light chain (NfL) as a biomarker for treatment responses in children with a broad spectrum of spinal muscular atrophy (SMA) under nusinersen treatment.

Method

We measured NfL levels in serum (sNfL) and cerebrospinal fluid (cNfL) in nusinersen-treated patients with SMA and children without neurologic disorders. Correlations between cNfL and sNfL levels and motor function scores were analyzed.

Results

sNfL and cNfL levels were measured in eight patients with SMA (SMA type 1, n = 3; SMA type 2, n = 5). sNfL levels were strongly correlated with cNfL levels regardless of the SMA subtype (r = 0.97, P < 0.001). Patients with SMA type 1 had higher baseline cNfL and sNfL levels before treatment initiation than those with SMA type 2 and neurologically healthy children. In patients with acute stage of SMA type 1 and 2, the NfL level rapidly decreased during the nusinersen treatment loading phase followed by stabilization at a lower plateau level. In contrast, in a patient with a chronic stage of SMA type 2, the NfL level remained within the normal range with no apparent downward trend. Motor function scores showed a tendency toward an inverse correlation with NfL levels in patients with acute stage although not in patients with chronic stage.

Conclusions

cNfL and sNfL levels can be promising biomarkers for monitoring treatment response in patients within their acute stage, particularly in SMA type 1, although not in patients with a chronic stage of SMA type 2.