片側巨脳症

Syndromic megalencephaly comprises a heterogeneous group of genetic disorders characterized by abnormal brain overgrowth and variable structural brain abnormalities. Prenatal recognition remains challenging because imaging findings overlap with those of isolated macrocephaly, while genotype-phenotype correlations are incompletely understood. This review summarizes the current literature on fetal magnetic resonance imaging (MRI) findings in molecularly confirmed syndromic megalencephaly and discusses their relationship with the underlying genetic pathways. The available evidence indicates that ventriculomegaly, malformations of cortical development, asymmetric lateral ventricles, hemimegalencephaly, and enlarged extra-axial spaces represent the most frequently reported prenatal MRI abnormalities, although their prevalence varies among genetic subgroups. Emerging imaging patterns suggest pathway-specific associations, particularly between the PIK3CA-AKT-mTOR pathway and hemimegalencephaly, and between RASopathies and enlarged extra-axial spaces. Current evidence is derived predominantly from case reports and small case series, underscoring the rarity of these disorders and the limited availability of systematic prenatal imaging data. Integrating fetal MRI findings with molecular diagnosis may improve prenatal diagnosis, facilitate targeted genetic testing, enhance prenatal counseling, and provide a foundation for future imaging-based diagnostic frameworks in syndromic megalencephaly.

The phosphatidylinositol-3-kinase (PI3K)-AKT-mTOR pathway plays a central role in cellular growth and survival, and somatic activating variants in PIK3CA cause PIK3CA-related overgrowth spectrum (PROS). Because these variants arise postzygotically, affected individuals exhibit somatic mosaicism, making molecular diagnosis challenging, particularly when only peripheral blood is available. We report an infant with PROS presenting with hemimegalencephaly, facial infiltrating lipomatosis, epidermal nevi, and unilateral woolly hair. A hotspot PIK3CA variant (c.1633G>A, p.Glu545Lys) was identified in the resected brain tissue but not in the peripheral blood. Notably, the variant was detected in DNA extracted from hair follicles of curly hair on the affected side of the scalp, whereas it was absent in follicles from straight hair on the contralateral side. Droplet digital PCR demonstrated variant allele fractions of 24.7%-27.6% in brain tissue and 32.3% in curly hair. These findings highlight the utility of hair follicles as a minimally invasive and accessible source of DNA for detecting somatic mosaic variants in PROS. The spatial concordance between genotype and hair phenotype suggests a possible association between PIK3CA mosaicism and localized hair abnormalities, although causality remains to be established.

OBJECTIVE: Surgery is increasingly recognized as an effective treatment for drug-resistant epilepsy in children but remains under-utilized. Evidence on its safety and benefits in infants 6 months or younger is very limited, leaving early surgical decision-making insufficiently supported. METHODS: A matched cohort study included 23 infants with age-dependent epileptic encephalopathy (ADEE) and structural brain abnormalities who underwent epilepsy surgery within 6 months and 115 matched non-surgical controls. Neurodevelopment was assessed using developmental quotient (DQ). Multivariable linear regression and propensity score matching (PSM) were used to examine the association between surgery and neurodevelopmental outcomes, whereas surgical safety and long-term seizure control were also evaluated. RESULTS: Among the 23 surgical infants, the median age at seizure onset was .27 months, and all had congenital brain malformations. Hemimegalencephaly was the most common etiology (n = 13). The mean age at surgery was 3.5 months. Hemispherotomy was the most commonly performed surgical procedure (n = 14). No perioperative death or permanent severe complications were observed. Four (17.4%) infants developed transient unilateral limb weakness and 13.6% had postoperative hydrocephalus. The rate of Engel class Ia was 82.6% at 1 year postoperatively and 78.2% at a mean follow-up of 44.4 months. At last follow-up, 69.6% of the infants had discontinued anti-seizure medications (ASMs). The DQ scores of the control group showed a continuous decline over time, whereas the surgical group showed a more favorable trajectory. Multivariable linear regression analysis revealed that surgery was significantly associated with a higher DQ (β = 30.2, 95% confidence interval [CI]: 19.5-40.9; p < .001). After 1:1 PSM to control confounding variables, the surgical group had significantly higher DQ scores than the control group in all five neurodevelopmental domains (p < .05). SIGNIFICANCE: Epilepsy surgery performed by an experienced team is safe and feasible for very young infants due to congenital brain malformations, without severe perioperative complications. It provides good long-term seizure control, supports ASM withdrawal, and may protect brain development, potentially stabilizing or even improving neurodevelopment in some infants.

BACKGROUND: Hemimegalencephaly is characterized by unihemispheric hypertrophy, early-onset intractable epilepsy, and developmental delay. Staged transarterial embolization (TAE) was developed to reduce seizure burden in infants. This study characterizes the seizure profiles and management of infants treated with TAE. METHODS: Retrospective review of infants <3 months at Children's National Hospital from 2018 to 2023, including demographics, seizure profile, and medication management. RESULTS: Eight infants underwent TAE. The mean age of seizure onset was 9 (0-28) days old, and the average age of first embolization was 50 (13-99) days old. Four patients underwent three stages, three patients had four stages, and one patient had five stages. In the first week of seizure onset, 6 (75%) patients had focal impaired consciousness seizures with elementary motor phenomena and 3 (50%) developed epileptic spasms later. Additionally, 2 (25%) had focal impaired consciousness seizures with autonomic or cognitive phenomena. In the 24 hours before the first embolization, 6 (75%) patients had frequent recurrent electrographic seizures and one (17%) had frequent recurrent electroclinical seizures. At discharge, electrographic seizure freedom was achieved in 6 (75%) of patients, and rare electrographic-only seizures in 2 (25%) patients. One (13%) patient was seizure-free on the megalencephalic hemisphere but developed seizures on the contralateral hemisphere. Patients had a median of 8 antiseizure medications during admission but weaned to a median of 4 medications at discharge. CONCLUSIONS: All patients achieved complete resolution of electroclinical seizures from the affected hemisphere. Infants require escalation of antiseizure medications transiently, but after the final TAE, decreased to more typical epilepsy polytherapy.

Knowledge in the spectrum of epidermal nevi and epidermal nevus syndrome has been elaborated on and expanded rapidly through the years. In this review, we provide a comprehensive overview of the neurologic manifestations of epidermal nevus syndromes (ENS), with a particular focus on epilepsy, which represents one of the most disabling and frequent systemic complications. Although ENS comprises a heterogeneous group of neurocutaneous syndromes unified by the presence of epidermal hamartomas and extracutaneous involvement, the relationship between genotype, cutaneous phenotype, and seizure phenotype remains incompletely understood. We systematically outline the epileptogenic potential of the 10 well-characterized ENS subtypes, highlighting the distinct seizure types, electroencephalographic findings, and associated structural brain anomalies such as hemimegalencephaly, cortical dysplasia, and neuronal heterotopias. Particular emphasis is placed on subtypes with a high seizure burden, including keratinocytic epidermal nevus syndrome, nevus sebaceus syndrome, phakomatosis pigmentokeratotica, nevus comedonicus syndrome, and angora hair nevus syndrome. For each, we examine the available evidence on seizure semiology, electroencephalographic correlates, radiologic features, and outcomes. Additionally, we review current management strategies, including both medical and surgical approaches to epilepsy in ENS, and discuss the emerging role of molecular targeted therapies. Through this review, we aim to underscore the importance of early diagnostic evaluation in patients presenting with epidermal nevi and to support multidisciplinary approaches for seizure control and long-term neurologic outcomes.