RESUMEN
KRAS gain-of-function mutations are frequently observed in sporadic arteriovenous malformations. The mechanisms underlying the progression of such KRAS-driven malformations are still incompletely understood, and no treatments for the condition are approved. Here, we show the effectiveness of sotorasib, a specific KRAS G12C inhibitor, in reducing the volume of vascular malformations and improving survival in two mouse models carrying a mosaic Kras G12C mutation. We then administered sotorasib to two adult patients with severe KRAS G12C-related arteriovenous malformations. Both patients had rapid reductions in symptoms and arteriovenous malformation size. Targeting KRAS G12C appears to be a promising therapeutic approach for patients with KRAS G12C-related vascular malformations. (Funded by the European Research Council and others.).
Asunto(s)
Proteínas Proto-Oncogénicas p21(ras) , Ratones , Animales , Humanos , Proteínas Proto-Oncogénicas p21(ras)/genética , Femenino , Masculino , Malformaciones Arteriovenosas/genética , Adulto , Piridinas/uso terapéutico , Modelos Animales de Enfermedad , Mutación , Persona de Mediana Edad , Mutación con Ganancia de Función , Piperazinas/uso terapéutico , PirimidinasRESUMEN
The craniocervical junction (CCJ) forms the bridge between the skull and the spine, a highly mobile group of joints that allows the mobility of the head in every direction. The CCJ plays a major role in protecting the inferior brainstem (bulb) and spinal cord, therefore also requiring some stability. Children are subjected to multiple constitutive or acquired diseases involving the CCJ: primary bone diseases such as in FGFR-related craniosynostoses or acquired conditions such as congenital torticollis, cervical spine luxation, and neurological disorders. To design efficient treatment plans, it is crucial to understand the relationship between abnormalities of the craniofacial region and abnormalities of the CCJ. This can be approached by the study of control and abnormal growth patterns. Here we report a model of normal skull base growth by compiling a collection of geometric models in control children. Focused analyses highlighted specific developmental patterns for each CCJ bone, emphasizing rapid growth during infancy, followed by varying rates of growth and maturation during childhood and adolescence until reaching stability by 18 years of age. The focus was on the closure patterns of synchondroses and sutures in the occipital bone, revealing distinct closure trajectories for the anterior intra-occipital synchondroses and the occipitomastoid suture. The findings, although based on a limited dataset, showcased specific age-related changes in width and closure percentages, providing valuable insights into growth dynamics within the first 2 years of life. Integration analyses revealed intricate relationships between skull and neck structures, emphasizing coordinated growth at different stages. Specific bone covariation patterns, as found between the first and second cervical vertebrae (C1 and C2), indicated synchronized morphological changes. Our results provide initial data for designing inclusive CCJ geometric models to predict normal and abnormal growth dynamics.
RESUMEN
Pediatric spinal low-grade glioma (LGG) and glioneuronal tumours are rare, accounting for less 2.8-5.2% of pediatric LGG. New tumour types frequently found in spinal location such as diffuse leptomeningeal glioneuronal tumours (DLGNT) have been added to the World Health Organization (WHO) classification of tumours of the central nervous system since 2016, but their distinction from others gliomas and particularly from pilocytic astrocytoma (PA) are poorly defined. Most large studies on this subject were published before the era of the molecular diagnosis and did not address the differential diagnosis between PAs and DLGNTs in this peculiar location. Our study retrospectively examined a cohort of 28 children with LGGs and glioneuronal intramedullary tumours using detailed radiological, clinico-pathological and molecular analysis. 25% of spinal PAs were reclassified as DLGNTs. PA and DLGNT are nearly indistinguishable in histopathology or neuroradiology. 83% of spinal DLGNTs presented first without leptomeningeal contrast enhancement. Unsupervised t-distributed stochastic neighbor embedding (t-SNE) analysis of DNA methylation profiles showed that spinal PAs formed a unique methylation cluster distinct from reference midline and posterior fossa PAs, whereas spinal DLGNTs clustered with reference DLGNT cohort. FGFR1 alterations were found in 36% of spinal tumours and were restricted to PAs. Spinal PAs affected significantly younger patients (median age 2 years old) than DLGNTs (median age 8.2 years old). Progression-free survival was similar among the two groups. In this location, histopathology and radiology are of limited interest, but molecular data (methyloma, 1p and FGFR1 status) represent important tools differentiating these two mitogen-activated protein kinase (MAPK) altered tumour types, PA and DLGNT. Thus, these molecular alterations should systematically be explored in this type of tumour in a spinal location.
Asunto(s)
Astrocitoma , Neoplasias Encefálicas , Neoplasias del Sistema Nervioso Central , Glioma , Humanos , Niño , Preescolar , Estudios Retrospectivos , Astrocitoma/patología , Neoplasias del Sistema Nervioso Central/genética , Glioma/genética , Epigénesis Genética , Neoplasias Encefálicas/genéticaRESUMEN
BACKGROUND AND PURPOSE: Pediatric nontraumatic intracerebral hemorrhage accounts for half of stroke in children. Early diagnostic of the causative underlying lesion is the first step toward prevention of hemorrhagic recurrence. We aimed to investigate the performance of arterial spin labeling sequence (ASL) in the acute phase etiological workup for the detection of an arteriovenous shunt (AVS: including malformation and fistula), the most frequent cause of pediatric nontraumatic intracerebral hemorrhage. METHODS: Children with a pediatric nontraumatic intracerebral hemorrhage between 2011 and 2019 enrolled in a prospective registry were retrospectively included if they had undergone ASL-magnetic resonance imaging before any etiological treatment. ASL sequences were reviewed using cerebral blood flow maps by 2 raters for the presence of an AVS. The diagnostic performance of ASL was compared with admission computed tomography angiography, other magnetic resonance imaging sequences including contrast-enhanced sequences and subsequent digital subtraction angiography. RESULTS: A total of 121 patients with pediatric nontraumatic intracerebral hemorrhage were included (median age, 9.9 [interquartile range, 5.8-13]; male sex 48.8%) of whom 76 (63%) had a final diagnosis of AVS. Using digital subtraction angiography as an intermediate reference, visual ASL inspection had a sensitivity and a specificity of, respectively, 95.9% (95% CI, 88.5%-99.1%) and 79.0% (95% CI, 54.4%-94.0%). ASL had a sensitivity, specificity, and accuracy of 90.2%, 97.2%, and 92.5%, respectively for the detection of the presence of an AVS, with near perfect interrater agreement (κ=0.963 [95% CI, 0.912-1.0]). The performance of ASL alone was higher than that of other magnetic resonance imaging sequences, individually or combined, and higher than that of computed tomography angiography. CONCLUSIONS: ASL has strong diagnostic performance for the detection of AVS in the initial workup of intracerebral hemorrhage in children. If our findings are confirmed in other settings, ASL may be a helpful diagnostic imaging modality for patients with pediatric nontraumatic intracerebral hemorrhage. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: 3618210420, 2217698.
Asunto(s)
Angiografía de Substracción Digital/métodos , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/etiología , Marcadores de Spin , Tomografía Computarizada por Rayos X/métodos , Adolescente , Fístula Arteriovenosa/complicaciones , Fístula Arteriovenosa/diagnóstico por imagen , Fístula Arteriovenosa/fisiopatología , Hemorragia Cerebral/fisiopatología , Circulación Cerebrovascular/fisiología , Niño , Preescolar , Femenino , Humanos , Malformaciones Arteriovenosas Intracraneales/complicaciones , Malformaciones Arteriovenosas Intracraneales/diagnóstico por imagen , Malformaciones Arteriovenosas Intracraneales/fisiopatología , Masculino , Estudios Prospectivos , Sistema de Registros , Estudios RetrospectivosRESUMEN
BACKGROUND AND PURPOSE: Significant hemorrhage expansion (sHE) is a known predictor of poor outcome after an intracerebral hemorrhage (ICH) in adults but remains poorly reported in children. In a large inception cohort, we aimed to explore the prevalence of sHE, its associations with clinical outcomes, and its clinical-imaging predictors in children. METHODS: Children admitted between January 2000 and March 2020 at a quaternary care pediatric hospital were screened for inclusion. Sample was restricted to children with 2 computed tomography scans within 72 hours of ICH onset, and a minimal clinical follow-up of months. sHE was defined as an increase from baseline ICH volume by 6 cc or 33% on follow-up computed tomography. Clinical outcome was assessed at 12 months with the King's Outcome Scale for Childhood Head Injury score and defined as favorable for scores ≥5. RESULTS: Fifty-two children met inclusion criteria, among which 8 (15%) demonstrated sHE, and 18 (34.6%) any degree of expansion. Children with sHE had more frequent coagulation disorders (25.0% versus 2.3%; P=0.022). After multivariable adjustment, only the presence of coagulation disorders at baseline remained independently associated with sHE (adjusted odds ratio, 14.4 [95% CI, 1.04-217]; P=0.048). sHE was independently associated with poor outcome (King's Outcome Scale for Childhood Head Injury <5A, odds ratio, 5.77 [95% CI, 1.01-38.95]; P=0.043). CONCLUSIONS: sHE is a frequent phenomenon after admission for a pediatric ICH and more so in children with coagulation defects. As sHE was strongly associated with poorer clinical outcomes, these data mandate a baseline coagulation work up and questions the need for protocolized repeat head computed tomography in children admitted for pediatric ICH.
Asunto(s)
Hemorragia Cerebral/patología , Adolescente , Trastornos de la Coagulación Sanguínea/complicaciones , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/epidemiología , Niño , Preescolar , Estudios de Cohortes , Traumatismos Craneocerebrales/complicaciones , Femenino , Estudios de Seguimiento , Escala de Coma de Glasgow , Humanos , Masculino , Oportunidad Relativa , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Tomografía Computarizada por Rayos X , Resultado del TratamientoAsunto(s)
Éxito Académico , Actividades Cotidianas , Hemorragia Cerebral/fisiopatología , Cognición , Adolescente , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/genética , Anticoagulantes/efectos adversos , Fístula Arteriovenosa/complicaciones , Fístula Arteriovenosa/genética , Trastornos de la Coagulación Sanguínea/complicaciones , Neoplasias Encefálicas/complicaciones , Malformaciones Vasculares del Sistema Nervioso Central/complicaciones , Malformaciones Vasculares del Sistema Nervioso Central/genética , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/etiología , Hemorragia Cerebral/terapia , Niño , Preescolar , Disfunción Cognitiva , Angiografía por Tomografía Computarizada , Descompresión Quirúrgica , Drenaje , Educación Especial , Cefalea , Hemangioma Cavernoso del Sistema Nervioso Central/complicaciones , Hemangioma Cavernoso del Sistema Nervioso Central/genética , Humanos , Lactante , Malformaciones Arteriovenosas Intracraneales/complicaciones , Malformaciones Arteriovenosas Intracraneales/genética , Angiografía por Resonancia Magnética , Enfermedad de Moyamoya/complicaciones , Enfermedad de Moyamoya/genética , Procedimientos Neuroquirúrgicos , Rendimiento Físico Funcional , Pronóstico , Integración Social , VómitosRESUMEN
Genetic diseases with craniofacial malformations can be associated with anomalies of the craniocervical joint (CCJ). The functions of the CCJ are thus impaired, as mobility may be either limited by abnormal bone fusion causing headaches, or exaggerated in the case of hypermobility, which may cause irreparable damage to the spinal cord. Restoring the balance between mobility and stability requires surgical correction in children. The anatomy and biomechanics of the CCJ are quite unique, yet have been overlooked in the past decades. Pediatric evidence is so scarce, that investigating the adult CCJ is our best shot to disentangle the form-function relationships of this anatomical region. The motivation of the present study was to understand the morphological and functional basis of motion in the CCJ, in the hope to find morphological features accessible from medical imaging able to predict mobility. To do so, we have quantified the in-vitro kinematics of the CCJ in nine cadaveric asymptomatic adults, and estimated a wide range of mobility variables covering the complexity of spinal motion. We compared these variables with the shape of the occipital, the atlas and the axis, obtained using a dense geometric morphometric approach. Morphological joint congruence was also quantified. Our results suggest a strong relationship between bone shape and motion, with the overall geometry predicting best the primary movements, and the joint facets predicting best the secondary movements. We propose a functional hypothesis stating that the musculoligamental system determines movements of great amplitude, while the shape and congruence of joint facets determine the secondary and coupled movements, especially by varying the geometry of bone stops and the way ligaments are tensioned. We believe this work will provide valuable insights in understanding the biomechanics of the CCJ. Furthermore, it should help surgeons treating CCJ anomalies by enabling them to translate objectives of functional and clinical outcome into clear objectives of morphological outcome.
Asunto(s)
Cadáver , Humanos , Fenómenos Biomecánicos , Adulto , Masculino , Femenino , Rango del Movimiento Articular , Articulación Atlantooccipital/anatomía & histología , Vértebras Cervicales/anatomía & histología , Persona de Mediana Edad , Anciano , Articulación Atlantoaxoidea/anatomía & histologíaRESUMEN
Diffuse midline glioma with two components: classical glial and ependymal.
Asunto(s)
Neoplasias Encefálicas , Glioma , Humanos , Glioma/genética , Neoplasias Encefálicas/genética , Histonas , Neuroglía , Receptores ErbB/genéticaRESUMEN
CONTEXT: Outcome of craniopharyngioma is related to its locoregional extension, which impacts resectability and the risk of surgical complications. To maximize resection and minimize complications, optic tract localization, temporal lobe extension, and hypothalamic involvement are essential factors for surgical management. OBJECTIVE: To assess the outcome of craniopharyngiomas depending on their relation to the hypothalamus location. METHODS: We conducted a retrospective analysis of 79 patients with a craniopharyngioma who underwent surgery from 2007 to 2022. Craniopharyngiomas were classified in 3 groups, depending on the type of hypothalamus involvement assessed by preoperative magnetic resonance imaging: infra-hypothalamic (type A, n = 33); perforating the hypothalamus (type B, n = 40); and supra-hypothalamic (type C, n = 6). Surgical strategy was guided by the type of hypothalamic involvement, favoring endonasal approaches for type A and type B, and transcranial approaches for type C. RESULTS: Long-term disease control was achieved in 33/33 (100%), 37/40 (92%), and 5/6 (83%) patients in type A, B, and C, respectively. In type B, vision was improved in 32/36 (89%) patients, while hypothalamic function was improved, stable, or worsened in 6/40 (15%), 32/40 (80%), and 2/40 (5%) patients, respectively. Papillary craniopharyngiomas were found in 5/33 (15%), 9/40 (22%), and 3/6 (50%) patients in types A, B, and C, respectively. In 4 patients, BRAF/MEK inhibitors were used, with significant tumor shrinkage in all cases. CONCLUSION: Craniopharyngiomas located below the hypothalamus or perforating it can be safely treated by transsphenoidal surgery. For supra-hypothalamic craniopharyngiomas, postoperative results are less favorable, and documenting a BRAF mutation may improve outcome, if targeted therapy was efficient enough to replace surgical debulking.
Asunto(s)
Craneofaringioma , Hipotálamo , Neoplasias Hipofisarias , Humanos , Craneofaringioma/cirugía , Craneofaringioma/complicaciones , Craneofaringioma/diagnóstico por imagen , Masculino , Femenino , Estudios Retrospectivos , Adulto , Neoplasias Hipofisarias/cirugía , Neoplasias Hipofisarias/complicaciones , Neoplasias Hipofisarias/patología , Neoplasias Hipofisarias/diagnóstico por imagen , Hipotálamo/patología , Hipotálamo/cirugía , Hipotálamo/diagnóstico por imagen , Persona de Mediana Edad , Pronóstico , Adulto Joven , Anciano , Adolescente , Imagen por Resonancia Magnética , Procedimientos Neuroquirúrgicos , Resultado del Tratamiento , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Estudios de Cohortes , Estudios de SeguimientoRESUMEN
BACKGROUND: Hydrocephalus frequently occurs with midline posterior fossa cystic collections. The classification of this heterogeneous group of developmental anomalies, including Dandy-Walker malformation, persisting Blake's pouch, retrocerebellar arachnoid cysts, and mega cisterna magna, is subject of debate. The absence of diagnostic criteria is confusing regarding the ideal management of PFCC-related hydrocephalus. OBJECTIVE: To decipher the surgical strategy for the treatment of children with PFCC-related hydrocephalus through a retrospective analysis of the surgical outcome driven by their clinical and radiological presentation. METHODS: This study enrolled patients operated of symptomatic PFCC-related hydrocephalus. Clinical and MRI features were examined, as well as the surgical outcome. Unbiased subgroup classification of the patients was performed with multiple component analysis as a function of imaging characteristics and hierarchical clustering on principal component. Outcome was assessed with binomial logistic regression and Kaplan-Meier analysis. RESULTS: Fifty-four patients were included between 2007 and 2021. Multiple component analysis suggested that cerebellar and vermian hypoplasia, vermian rotation, basal-tentorial angle, and fastigial angle were strongly correlated. Hierarchical clustering and the distribution of the patients in the bidimensional plot showed the clear segregation of 3 major clusters, which correlated with the radiological diagnosis ( P < .01). Binomial logistic regression and survival analysis showed that endoscopic third ventriculostomy was an effective treatment for patients with persisting Blake's pouch, while failing to control hydrocephalus in most of patients with Dandy-Walker malformation. CONCLUSION: Preoperative MRI in patients with PFCC-related hydrocephalus is essential to better define the diagnosis. The choice of treatment strategy notably relies on correct radiological diagnosis.
Asunto(s)
Quistes Aracnoideos , Síndrome de Dandy-Walker , Hidrocefalia , Humanos , Niño , Síndrome de Dandy-Walker/complicaciones , Síndrome de Dandy-Walker/diagnóstico por imagen , Síndrome de Dandy-Walker/cirugía , Estudios Retrospectivos , Hidrocefalia/diagnóstico por imagen , Hidrocefalia/etiología , Hidrocefalia/cirugía , Cerebelo , Imagen por Resonancia Magnética/métodos , Fosa Craneal Posterior/diagnóstico por imagen , Fosa Craneal Posterior/cirugíaRESUMEN
Background: The co-occurrence of moyamoya vasculopathy and extra-optic pathway tumors is rare in neurofibromatosis type 1 (NF1), with only four cases described in the literature. Brain surgery in these patients may be challenging because of the risk of brain infarction after skin and dural incision. Given its percutaneous and minimally invasive nature, laser interstitial thermal therapy (LITT) is an ideal option for the treatment of brain tumors in these patients. Here, we report on two patients with NF1 and moyamoya syndrome (MMS) treated for a brain glioma with LITT, after cerebral revascularization. Cases: The first patient, with familial NF1, underwent bilateral indirect revascularization with multiple burr holes (MBH) for symptomatic MMS. Two years later, she was diagnosed with a left temporal tumor, with evidence of radiologic progression over 10 months. The second patient, also with familial NF1, developed unilateral MMS when he was 6 years old and was treated with MBH. At the age of 15 years, MRI showed a right cingular lesion, growing on serial MRIs. Both patients underwent LITT with no perioperative complications; they are progression free at 10 and 12 months, respectively, and the tumors have decreased in volume. Discussion: While the association of extra-optic neoplasm and moyamoya angiopathy is seldom reported in NF1, tumor treatment is challenging in terms of both avoiding stroke and achieving oncological control. Here, we show in 2 cases, that LITT could be a safe and effective option in these rare conditions.
RESUMEN
OBJECTIVE: Epidural hematoma (EDH) has rarely been studied specifically in infants. The objective of this study was to investigate the outcomes of patients aged < 18 months (infants) with EDH. METHODS: The authors conducted a single-center retrospective study of 48 infants aged less than 18 months who underwent an operation for a supratentorial EDH in the last decade. Clinical, radiological, and biological variables were used in a statistical analysis to identify factors predictive of radiological and clinical outcome. RESULTS: Forty-seven patients were included in the final analysis. Seventeen children (36%) had cerebral ischemia on postoperative imaging, either due to stroke (cerebral herniation) or by local compression. Factors associated with ischemia after multivariate logistic regression were the presence of an initial neurological deficit (76% vs 27%, p = 0.03), low platelet count (mean 192 vs 267 per mm3, p = 0.01), low fibrinogen level (mean 1.4 vs 2.2 g/L, p = 0.04) and long intubation time (mean 65.7 vs 10.1 hours, p = 0.03). Cerebral ischemia on MRI was predictive of a poor clinical outcome. CONCLUSIONS: Infants with EDH have a low mortality rate but a high risk of cerebral ischemia, along with long-term neurological sequelae.
RESUMEN
OBJECTIVE: The outcome of endoscopic third ventriculostomy (ETV) in children who had previously received shunts and who were experiencing shunt dysfunction is still discussed in terms of efficacy (success rate from 40% to 80%) and safety (0%-32.5% of complications). Reported predictive factors of secondary ETV failure are age, early onset of hydrocephalus, and prematurity. The best surgical strategy in the different subgroups of patients with shunt dysfunction is still debated. Therefore, the authors aimed to identify subgroups of patients in whom shunt treatment was associated with favorable outcome of ETV, to define the role of ETV in patients with global rostral midbrain dysfunction syndrome. METHODS: This study was a monocentric retrospective case series and a meta-analysis of children who had previously received shunts and who underwent secondary ETV for shunt dysfunction between 2012 and 2022. Clinical and MRI features were examined, along with surgical outcome, etiology of hydrocephalus, and preoperative ETV Success Score. Univariate and multivariate analyses were performed to find predictors of outcome of secondary ETV. Youden's J index was calculated on age distribution to find an optimal age cutoff. Systematic review of the literature and a meta-analysis were performed according to the PRISMA statement. RESULTS: Seventy consecutive patients were included. The overall success rate of secondary ETV was 63%. Primary obstructive hydrocephalus, age ≥ 36 months, and the presence of aqueductal obstruction were predictors of ETV success. Multivariate analysis found that age < 36 months, primary inflammatory hydrocephalus, and presence of fourth ventricular obstruction were associated with ETV failure. All patients with global rostral midbrain dysfunction syndrome experienced clinical and radiological improvement after ETV. The meta-analysis showed that postinflammatory etiology and age < 36 months were predictors of ETV failure. CONCLUSIONS: ETV is safe and effective for children with obstructive hydrocephalus experiencing shunt dysfunction, notably in cases of primary obstructive hydrocephalus with aqueductal stenosis, and among children whose age was ≥ 36 months who had postinflammatory hydrocephalus.
Asunto(s)
Hidrocefalia , Neuroendoscopía , Tercer Ventrículo , Niño , Preescolar , Humanos , Lactante , Hidrocefalia/diagnóstico por imagen , Hidrocefalia/etiología , Hidrocefalia/cirugía , Neuroendoscopía/efectos adversos , Estudios Retrospectivos , Tercer Ventrículo/diagnóstico por imagen , Tercer Ventrículo/cirugía , Resultado del Tratamiento , Ventriculostomía/efectos adversosRESUMEN
OBJECTIVE: This study aimed to assess the relevance of using multi-positional MRI (mMRI) to identify cranio-vertebral junction (CVJ) instability in pediatric patients with CVJ anomalies while determining objective mMRI criteria to detect this condition. MATERIAL AND METHODS: Data from children with CVJ anomalies who underwent a mMRI between 2017 and 2021 were retrospectively reviewed. Mobility assessment using mMRI involved: (1) morphometric analysis using hierarchical clustering on principal component analysis (HCPCA) to identify clusters of patients by considering their mobility similarities, assessed through delta (Δ) values of occipito-cervical parameters measured on mMRI; and (2) morphological analysis based on dynamic geometric CVJ models and analysis of displacement vectors between flexion and extension. Receiver operating characteristics (ROC) curves were generated for occipito-cervical parameters to establish instability cut-off values. (3) Additionally, an anatomical qualitative analysis of the CVJ was performed to identify morphological criteria of instability. RESULTS: Forty-seven patients with CVJ anomalies were included (26 females, 21 males; mean age: 10.2 years [3-18]). HCPCA identified 2 clusters: cluster â1 (stable patients, n = 39) and cluster â2 (unstable patients, n = 8). ΔpB-C2 (pB-C2 line delta) at ≥2.5 mm (AUC 0.98) and ΔBAI (Basion-axis Interval delta) ≥ 3 mm (AUC 0.97) predicted instability with 88% sensibility and 95% specificity and 88% sensitivity and 85% specificity, respectively. Geometric CVJ shape analysis differentiated patients along a continuum, from a low to a high CVJ motion that was characterized by a subluxation of C1 in the anterior direction. Qualitative analysis found correlations between instability and C2 anomalies, including fusions with C3 (body p = 0.032; posterior arch p = 0.045; inferior articular facets p = 0.012; lateral mass p = 0.029). CONCLUSIONS: We identified a cluster of pediatric patients with CVJ instability among a cohort of CVJ anomalies that were characterized by morphometric parameters with corresponding cut-off values that could serve as objective mMRI criteria. These findings warrant further validation through prospective case-control studies.
RESUMEN
Zolpidem is a sedative drug that has been shown to induce a paradoxical effect, restoring brain function in wide range of neurological disorders. The underlying functional mechanism of the effect of zolpidem in the brain in clinical improvement is still poorly understood. Thus, we aimed to investigate rest brain function to study zolpidem-induced symptom improvement in a patient who developed postoperative pediatric cerebellar mutism syndrome, a postoperative complication characterized by delayed onset transient mutism/reduced speech that can occur after medulloblastoma resection. The patient experienced clinical recovery after a single dose of zolpidem. Brain function was investigated using arterial spin labeling MRI and resting-state functional MRI. Imaging was performed at three time-points: preoperative, postoperative during symptoms, and after zolpidem intake when the symptoms regressed. Whole brain rest cerebral blood flow (CBF) and resting state functional connectivity using Pearson coefficient correlations between pairs of regions of interest were investigated two-by-two at the different time points. A comparison between postoperative and preoperative images showed a significant decrease in rest CBF in the left supplementary motor area, Broca's area, and the left striatum and a decrease in functional connectivity within the dentato-thalamo-cortical and cortico-striato-pallido-thalamo-cortical loops. Post-zolpidem images showed increased CBF in the left striatum and increased functional connectivity within the disrupted loops relative to postoperative images. Thus, we observed functional changes within the broader speech network and thalamo-subcortical interactions associated with the paradoxical effect of zolpidem in promoting clinical recovery. This should encourage further functional investigations in the brain to better understand the mechanism of zolpidem in neurological recovery.
RESUMEN
OBJECTIVE: Brainstem cavernous malformations (BSCMs) are relatively uncommon, low-flow vascular lesions in children. Given the paucity of data, guidelines regarding the clinical management of BSCMs in children are lacking and the surgical indication is most commonly based on an individual surgeon's judgment and experience. The goal in this study was to evaluate the clinical behavior of BSCMs in childhood and the long-term outcome in children managed conservatively and surgically. METHODS: This was an observational, retrospective study including all children with BSCMs who were followed at 2 institutions between 2008 and 2020. RESULTS: The study population consisted of 40 children (27 boys, 67.5%) with a mean age of 11.4 years. Twenty-three children (57.5%) were managed conservatively, whereas 17 children (42.5%) underwent resection of BSCMs. An aggressive clinical course was observed in 13 children (32.5%), who experienced multiple hemorrhages with a progressive pattern of neurological decline. Multiple BSCMs were observed in 8 patients, of whom 3 patients presented with a complex of multiple tightly attached BSCMs and posed a significant therapeutic challenge. The overall long-term outcome was favorable (modified Rankin Scale [mRS] scores 0-2) in 36 patients (90%), whereas an unfavorable outcome (mRS scores 3 and 4) was seen in 4 children (10%). An mRS score of 5 or 6 was not observed. The mean (± SD) follow-up was 88.0 (± 92.6) months. CONCLUSIONS: The clinical course of BSCMs in children is highly variable, with benign lesions on the one hand and highly aggressive lesions with repetitive hemorrhages on the other. Given the greater life expectancy and the known higher functional recovery in children, surgical treatment should be considered early in young patients presenting with surgically accessible lesions and an aggressive clinical course, and it should be performed in a high-volume center.
Asunto(s)
Tronco Encefálico , Niño , Humanos , Masculino , Anomalías Múltiples , Tronco Encefálico/anomalías , Tronco Encefálico/patología , Tronco Encefálico/cirugía , Progresión de la Enfermedad , Hemangioma Cavernoso del Sistema Nervioso Central/diagnóstico por imagen , Hemangioma Cavernoso del Sistema Nervioso Central/cirugía , Procedimientos Neuroquirúrgicos , Estudios Retrospectivos , Resultado del Tratamiento , FemeninoRESUMEN
Importance: The COVID-19 pandemic and the containment and mitigation measures taken were feared to be associated with increased child abuse. Objective: To investigate the trend of abusive head trauma (AHT) incidence and severity in infants during the COVID-19 pandemic. Design, Setting, and Participants: In a time-series analysis of a longitudinal, population-based, cohort study, all consecutive cases of AHT in infants younger than 12 months old referred between January 2017 and December 2021 to Necker Hospital for Sick Children, the single regional pediatric neurosurgery center for the Paris metropolitan area, were included. AHT was defined as 1 or more subdural hemorrhage and a positive multidisciplinary evaluation after a social, clinical, biological, and radiological workup. Data were analyzed from January to March 2022. Main Outcomes and Measures: The primary outcome was the monthly incidence of AHT, which was analyzed using Poisson regression modeling. Secondary outcomes included mortality and severe morbidity and were studied with logistic and linear regressions. The monthly incidence of neurosurgical interventions for hydrocephalus was used as a control series. Results: Among the 99 included infants with AHT (median [IQR] age, 4 [3-6] months; 64 boys [65%]), 86 of 99 (87%) had bridging vein thrombosis, 74 of 99 (75%) had retinal hemorrhages, 23 of 72 (32%) had fractures, 26 of 99 (26%) had status epilepticus, 20 of 99 (20%) had skin injuries, 53 of 99 (54%) underwent neurosurgical interventions, and 13 of 99 (13%) died. Compared with the prepandemic period (2017-2019), AHT incidence was stable in 2020 (adjusted incidence rate ratio, 1.02; 95% CI, 0.59-1.77) and then significantly increased in 2021 (adjusted incidence rate ratio, 1.92; 95% CI, 1.23-2.99). The severity of AHT worsened in 2021 in terms of mortality (odds ratio 9.39; 95% CI, 1.88-47.00). Other secondary outcomes and the control series were not significantly modified. Conclusions and Relevance: In this cohort study, a marked increase in AHT incidence and severity occurred during the COVID-19 pandemic in the Paris metropolitan area. These results suggest the need for clinical awareness and preventive actions.
Asunto(s)
COVID-19 , Maltrato a los Niños , Traumatismos Craneocerebrales , COVID-19/epidemiología , Estudios de Cohortes , Traumatismos Craneocerebrales/epidemiología , Femenino , Humanos , Lactante , Masculino , Pandemias , Paris/epidemiologíaRESUMEN
OBJECTIVE: Chiari malformation type I (CM-I) is frequent in children and remains a surgical challenge. Several techniques have been described for posterior fossa decompression. No decision algorithm has been validated, and strategies are highly variable between institutions. The goal of this study was to define therapeutic guidelines that take into consideration patient specificities. METHODS: The authors retrospectively collected data from patients who were < 18 years of age, were diagnosed with CM-I, and were treated surgically between 2008 and 2018 in 8 French pediatric neurosurgical centers. Data on clinical features, morphological parameters, and surgical techniques were collected. Clinical outcomes at 3 and 12 months after surgery were assessed by the Chicago Chiari Outcome Scale. The authors used a hierarchical clustering method to define clusters of patients by considering their anatomical similarities, and then compared outcomes between surgical strategies in each of these clusters. RESULTS: Data from 255 patients were collected. The mean age at surgery was 9.6 ± 5.0 years, syringomyelia was reported in 60.2% of patients, the dura mater was opened in 65.0% of patients, and 17.3% of patients underwent a redo surgery for additional treatment. The mean Chicago Chiari Outcome Scale score was 14.4 ± 1.5 at 3 months (n = 211) and 14.6 ± 1.9 at 12 months (n = 157). The hierarchical clustering method identified three subgroups with potentially distinct mechanisms underlying tonsillar herniation: bony compression, basilar invagination, and foramen magnum obstruction. Each cluster matched with specific outcomes. CONCLUSIONS: This French multicenter retrospective cohort study enabled the identification of three subgroups among pediatric patients who underwent surgery for CM-I, each of which was associated with specific outcomes. This morphological classification of patients might help in understanding the underlying mechanisms and providing personalized treatment.
Asunto(s)
Malformación de Arnold-Chiari , Malformación de Arnold-Chiari/complicaciones , Niño , Estudios de Cohortes , Descompresión Quirúrgica/métodos , Duramadre/cirugía , Humanos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Recurrence following obliteration of brain arteriovenous malformations (AVMs) is common in children surgically treated, but recurrences following endovascular (EVT) and radiosurgical approaches are scantily reported. OBJECTIVE: To analyze the rates and risk factors for AVM recurrence after obliteration in a single-center cohort of children with ruptured AVMs treated with multimodal approaches, and to carry out a comprehensive review and meta-analysis of current data. METHODS: Children with ruptured AVMs between 2000 and 2019 enrolled in a prospective registry were retrospectively screened and included after angiographically determined obliteration to differentiate children with/without recurrence. A complementary systematic review and meta-analysis of studies investigating AVM recurrence in children between 2000 and 2020 was aggregated to explore the overall recurrence rates across treatment modalities by analyzing surgery versus other treatments. RESULTS: Seventy children with obliterated AVMs were included. AVM recurrences (n=10) were more commonly treated with EVT as final treatment (60% in the recurrence vs 13.3% in the no-recurrence group, p=0.018). Infratentorial locations were associated with earlier and more frequent recurrences (adjusted relative risk=4.62, 95% CI 1.08 to 19.04; p=0.04).In the aggregate analysis, the pooled rate of AVM recurrence was 10.9% (95% CI 8.7% to 13.5%). Younger age at presentation was associated with more frequent recurrences (RR per year increase, 0.97, 95% CI 0.93 to 0.99; p=0.046). CONCLUSION: Location of infratentorial AVMs and younger age at presentation may be associated with earlier and more frequent recurrences. The higher rates of recurrence in patients with AVMs obliterated with EVT questions its role in an intent-to-cure approach and reinforces its position as an adjunct to surgery and/or radiosurgery.
Asunto(s)
Malformaciones Arteriovenosas Intracraneales , Radiocirugia , Encéfalo , Niño , Estudios de Cohortes , Estudios de Seguimiento , Humanos , Malformaciones Arteriovenosas Intracraneales/diagnóstico por imagen , Malformaciones Arteriovenosas Intracraneales/cirugía , Recurrencia , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The International Society for the Study of Vascular Anomalies (ISSVA) has defined four vascular lesions in the central nervous system (CNS): arteriovenous malformations, cavernous angiomas (also known as cerebral cavernous malformations), venous malformations, and telangiectasias. From a retrospective central radiological and histopathological review of 202 CNS vascular lesions, we identified three cases of unclassified vascular lesions. Interestingly, they shared the same radiological and histopathological features evoking the cavernous subtype of angioleiomyomas described in the soft tissue. We grouped them together with four additional similar cases from our clinicopathological network and performed combined molecular analyses. In addition, cases were compared with a cohort of 5 soft tissue angioleiomyomas. Three out 6 CNS lesions presented the same p.Gly41Cys GJA4 mutation recently reported in hepatic hemangiomas and cutaneous venous malformations and found in 4/5 soft tissue angioleiomyomas of our cohort with available data. Most DNA methylation profiles were not classifiable using the CNS brain tumor (version 12.5), and sarcoma (version 12.2) classifiers. However, using unsupervised t-SNE analysis and hierarchical clustering analysis, 5 of the 6 lesions grouped together and formed a distinct epigenetic group, separated from the clusters of soft tissue angioleiomyomas, other vascular tumors, inflammatory myofibroblastic tumors and meningiomas. Our extensive literature review identified several cases similar to these lesions, with a wide variety of denominations. Based on radiological and histomolecular findings, we suggest the new terminology of "dural angioleiomyomas" (DALM) to designate these lesions characterized by a distinct DNA methylation pattern and frequent GJA4 mutations.