Journal of Child Neurology最新文献

Alexander disease (ALEXD; MIM 203450) is a rare leukodystrophy caused by dominant mutations in the GFAP (Glial Fibrillary Acidic Protein) gene, which encodes a key structural protein of astrocytes. First described in 1949, ALEXD is now recognized as a clinically heterogeneous disorder with a broad phenotypic spectrum spanning neonatal, infantile, juvenile, and adult-onset forms. Clinical manifestations vary according to age at onset and disease subtype, ranging from early developmental impairment and progressive neurologic decline to later-onset presentations dominated by bulbar dysfunction, ataxia, and spinal cord involvement. Diagnosis can be challenging because of phenotypic overlap with other neurologic conditions; however, characteristic magnetic resonance imaging patterns combined with molecular confirmation of GFAP mutations are central to diagnosis. To date, more than 100 GFAP mutations have been reported, although robust genotype-phenotype correlations remain elusive. Pathogenic GFAP variants lead to astrocyte dysfunction through protein aggregation, oxidative stress, and cytoskeletal disorganization, resulting in Rosenthal fiber formation. Elevated GFAP levels in cerebrospinal fluid have emerged as a potential biomarker, though their clinical utility remains under investigation. Current management is supportive, but emerging gene-targeted approaches, including antisense oligonucleotides such as zilganersen and AAV-mediated gene silencing strategies, offer promising therapeutic prospects. This review provides an updated overview of the clinical, radiologic, genetic, and molecular features of ALEXD, emphasizing its spectrum of phenotypes across age groups and ongoing efforts toward improved diagnosis and targeted treatment.

ObjectiveThis study evaluates neuroimaging findings in pediatric headache patients and identifies clinical predictors for imaging necessity.MethodsA retrospective analysis was performed on 1008 children aged 3-17 years presenting with headache between January 2023 and January 2025. Data on headache type, neurologic examination, and cranial magnetic resonance imaging (MRI) results were collected and classified per ICHD-3 criteria.ResultsOf the patients, 62.7% were girls and the mean age was 12.4 years. Migraine (27.0%) and tension-type headache (18.6%) were the most common diagnoses. Neurologic examinations were normal in 96.2%. MRI was conducted in 908 patients; 26.7% showed abnormalities, although only 3.6% were clinically significant (eg, pseudotumor cerebri, Chiari malformation). Significant findings correlated with abnormal neurologic examinations and sleep-disrupting headaches (P < .001, P = .0047). Headache duration was not predictive.ConclusionMost pediatric headaches are benign. Imaging should be limited to cases with abnormal examinations or clinical red flags.

BackgroundHeadache is the most common neurologic symptom among children and adolescents, with a point prevalence of 58%. Headache disorders, particularly migraine, are considered one of the most disabling conditions in childhood. Headaches may cause cognitive impairment; however, research on this symptom-particularly on its influence on executive functioning-remains limited. We aimed to examine the executive function among children and adolescents with primary headache disorder compared to controls. Determining executive problems is important, as it allows us to ensure appropriate support and intervention.MethodsThis cross-sectional case-control study was performed at the Department of Pediatrics and Adolescents Medicine, Copenhagen University Hospital, Herlev, Denmark. A total of 109 pediatric patients diagnosed with primary headache were recruited from the pediatric outpatient clinic, along with 112 controls without a headache diagnosis. Executive function was assessed using selected subtests from the Delis-Kaplan Executive Function System (D-KEFS): the Trail Making Test, the Figure Design Test, and the Verbal Fluency Test.ResultsAmong the patients, 31 were diagnosed with migraine, 31 with tension-type headache, 31 with mixed headache, and 16 with unclassified headache. A significance level of P <.05 was applied. Patients with headache performed significantly worse than controls on the Trail Making Test (P = .015). No statistically significant differences in executive function were observed between the migraine and tension-type headache subgroups.Among children with migraine, higher headache frequency was associated with poorer performance on the Verbal Fluency Test-Switching condition (P = .04). In children with mixed headache, higher headache frequency was similarly associated with poorer performance on the Trail Making Test-number-letter switching (P = .037).ConclusionWe found a significant difference between the patient and control group in one of the subtests, suggesting that headache could be associated with poorer executive function. Future studies are needed to examine the causality of this association.

Periodic reanalysis of genomic data plays a pivotal role in refining variant interpretation and resolving previously undiagnosed cases, particularly in the context of rare diseases. We report a female patient presenting with global developmental delay, drug-resistant epilepsy, optic atrophy, congenital heart defects, and craniofacial dysmorphism. An initially deprioritized heterozygous NOTCH1 variant (NM_017617.5: c.4787T>C; p.Leu1596Pro), previously associated with isolated cardiac phenotypes, was later reclassified as likely pathogenic following annual reanalysis through our institutional pipeline. Trio-based whole exome sequencing confirmed the variant's de novo origin, and emerging literature published in 2024 expanded the phenotypic spectrum of NOTCH1-related disorders to include neurologic, ocular, musculoskeletal, craniofacial, and integumentary features-closely mirroring the patient's presentation. This diagnostic refinement enabled tailored clinical management and informed genetic counseling. This case underscores the clinical utility of systematic genomic reanalysis in rare disease diagnostics, where evolving knowledge enables reclassification of previously uncertain variants. Moreover, this case adds to the growing body of evidence, broadening the recognized clinical and molecular landscape of NOTCH1-related disorders.

Nearly one-third of patients with epilepsy are unable to achieve adequate seizure control with medication alone. Responsive neurostimulation (RNS) of thalamic nuclei is a relatively new option for the treatment of drug-resistant epilepsy (DRE). Here the authors present a complex case of a pediatric patient with DRE secondary to left hemimegencephaly after anatomic hemispherectomy and vagal nerve stimulation. One year after undergoing right centromedian (CM) and anterior nucleus (ANT) thalamic RNS, the patient achieved a greater than 50% seizure frequency reduction. The technical challenges of targeting of the CM and ANT nuclei due to the lack of contralateral hemisphere and thalamus are discussed. Ultimately, the use of direct targeting with advanced MRI sequences allowed for successful targeting despite the challenges posed by the patient's unique anatomy.

Clinical phenotype expansion of neurodevelopmental disorders is increasingly important. With accessibility and diagnostic ability of genetic testing expanding, new clinical criteria will continue to be elucidated. Here we describe a case series of 4 female pediatric patients seen for global developmental delay in non-genetic, specialty clinics who received unexpected genetic diagnoses of MECP2-associated Rett syndrome (RS). These results highlight broadening clinical presentation for RS. None of the patients in this cohort met clinical RS diagnostic criteria at the time of genetic testing, as there was no period of typical development or developmental regression. These cases demonstrate both the importance of broad genomic sequencing for patients with global developmental delay and that increasing understanding of atypical and mild presentations of syndromes like RS will continue to evolve as genetic testing becomes standard of care for clinical features like developmental delay.

Management of the acute phase in steroid-unresponsive patients of myelin oligodendrocyte glycoprotein-associated disease (MOGAD) remains challenging, especially when there is no clinical improvement following a course of intravenous immunoglobulin (IVIG) which necessitates the need for reinfusion. The optimal timing of IVIG reinfusion in acute phase of MOGAD is a subject of debate. A 13-year-old South Indian boy presented with acute-onset paraparesis with urinary retention that progressed to quadriparesis within a week. Spine magnetic resonance imaging (MRI) spine revealed longitudinally extensive transverse myelitis from D2 to D7, whereas MRI brain showed subcortical white matter hyperintensities. Serum testing was strongly positive for myelin oligodendrocyte glycoprotein antibodies. Owing to persistent functional deficits following a course of IVIG, a reinfusion was administered at an interval of less than 2 weeks, shorter than the usual 3-4-week interval (corresponding to the half-life of IVIG) maintaining the presence and effectiveness of IVIG, leading to dramatic clinical improvement within a month.

BackgroundMumps is a highly neurotropic virus causing a wide variety of neurologic complications. Post-/para-infectious basal ganglia encephalitis is one of its rare complications, with higher morbidity compared with other complications.CasesWe present 5 cases with basal ganglia encephalitis secondary to mumps infection. A recent history of parotitis or febrile illness with serologic evidence of mumps, combined with acute onset of movement disorders, behavioral changes with or without seizures, and basal ganglia abnormalities on neuroimaging, suggests the diagnosis. The occurrence of extrapyramidal symptoms during recovery from a febrile illness, along with clinical improvement following immunomodulatory therapy, further supports the diagnosis.ConclusionPost-mumps basal ganglia encephalitis has higher morbidity than other mumps complications. Slower recovery and increased duration of hospitalization are noted. Including the mumps vaccine in routine immunization schedules is an effective way to prevent mumps and its associated basal ganglia encephalitis.

Brain monoamine vesicular transporter deficiency is a rare autosomal recessive neurometabolic disorder caused by mutations in the SLC18A2 gene, which encodes vesicular monoamine transporter 2 (VMAT2). VMAT2 is essential for packaging neurotransmitters such as dopamine, serotonin, norepinephrine, and histamine into synaptic vesicles. Its deficiency results in disrupted neurotransmission and a characteristic clinical syndrome involving developmental delay, hypotonia, movement disorders, and autonomic dysfunction. We report a novel homozygous frameshift variant, Chr10:119014792dupC (p.Phe238LeufsTer7), identified in a 5-month-old male from a consanguineous family, who presented with severe hypotonia, oculogyric crises, and developmental delay. This variant expands the known genotypic spectrum of SLC18A2-related disease. Our findings underscore the importance of early genetic testing in infants with unexplained movement disorders and support a multidisciplinary approach to care. We also compare this case to related neurometabolic disorders with overlapping clinical features and with prior SLC18A2 mutation-related disorder.