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PURPOSE: Supratentorial (ST) ependymoma subgroups are defined by two different fusions with different prognoses. Astroblastomas, MN1-altered, have ependymal-like histopathologic features and represent a differential diagnosis in children. We hypothesized that ZFTA-fused ependymoma and YAP1-fused ependymoma on the one hand, and astroblastoma, MN1-altered, on the other hand, show different MRI characteristics. METHODS: We retrospectively analyzed the preoperative imaging of 45 patients with ST ependymoma or astroblastoma between January 2000 and September 2020, blinded to histomolecular grouping. Several characteristics, such as location, tumor volume, calcifications, solid/cystic component, and signal enhancement or diffusion were evaluated. We compared imaging characteristics according to their molecular subtype (ZFTA-fused, YAP1-fused, and astroblastoma, MN1-altered). RESULTS: Thirty-nine patients were classified as having an ependymoma, 35 with a ZFTA fusion and four with a YAP1 fusion, and six as having an astroblastoma, MN1-altered. YAP1-fused ependymomas were more likely to involve at least 3 lobes than ZFTA-fused ependymomas. Astroblastomas were located in the frontal lobe in 100% of the tumors versus 49% of the ependymomas. Cerebral blood flow by arterial spin labeling was higher in astroblastomas than in ependymomas. There were no differences in the other characteristics between the molecular groups. All the tumors showed common features: intra-axial extra-ventricular tumors, very frequent contrast enhancement (39/43, 91%), a cystic/necrotic component (41/45, 91%), restricted diffusion (32/36, 89%), calcifications (15/18, 83%), and peri-tumoral edema (38/44, 86%). CONCLUSION: The distinction between ST ependymoma subtypes and astroblastomas can be guided by several imaging features. These tumors share common imaging features that may help to differentiate ST ependymomas and astroblastomas from other pediatric ST tumors.
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BACKGROUND: Children with constitutional mismatch repair deficiency (CMMRD) syndrome have an increased risk of high-grade gliomas (HGG), and brain imaging abnormalities. This study analyzes brain imaging features in CMMRD syndrome children versus those with HGG without CMMRD. METHODS: Retrospective comparative analysis of brain imaging in 30 CMMRD children (20 boys, median age eight years, 22 with HGG), seven with Lynch syndrome (7 HGG), 39 with type 1 neurofibromatosis (NF1) (four with HGG) and 50 with HGG without MMR or NF1 pathogenic variant ("no-predisposition" patients). RESULTS: HGG in CMMRD and Lynch patients were predominantly hemispheric (versus midline) compared to NF1 and no-predisposition patients (91% and 86%, vs 25% and 54%, p = 0.004). CMMRD-associated tumors often had ill-defined boundaries (p = 0.008). All CMMRD patients exhibited at least one developmental venous anomaly (DVA), versus 14%, 10%, and 6% of Lynch, NF1, and no-predisposition patients (p < 0.0001). Multiple DVAs were observed in 83% of CMMRD patients, one NF1 patient (3%), and never in other groups (p < 0.0001). Cavernomas were discovered in 21% of CMMRD patients, never in other groups (p = 0.01). NF1-like focal areas of high T2-FLAIR signal intensity (FASI) were more prevalent in CMMRD patients than in Lynch or no-predisposition patients (50%, vs 20% and 0%, respectively, p < 0.0001). Subcortical and ill-limited FASI, possibly involving the cortex, were specific to CMMRD (p < 0.0001) and did not evolve in 93% of patients (13/14). CONCLUSION: Diffuse hemispherically located HGG associated with multiple DVAs, cavernomas, and NF1-like or subcortical FASI strongly suggests CMMRD syndrome compared to children with HGG in other contexts. CLINICAL RELEVANCE STATEMENT: The radiologic suggestion of CMMRD syndrome when confronted with HGGs in children may prompt genetic testing. This can influence therapeutic plans. Therefore, imaging features could potentially be incorporated into CMMRD testing recommendations. KEY POINTS: Using imaging to detect CMMRD syndrome early may improve patient care. CMMRD features include: hemispheric HGG with multiple developmental venous anomalies and NF1-like or subcortical areas with high T2-FLAIR intensity. We propose novel imaging features to improve the identification of potential CMMRD patients.
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Background and Objectives: DNA polymerase subunit gamma (POLG) deficiency is likely the most frequent cause of nuclear-encoded mitochondrial disorders. POLG-related disorders reportedly constitute a spectrum of overlapping phenotypes from infancy to late adulthood. We retrospectively reviewed natural histories for 40 children carrying biallelic pathogenic POLG variants. Methods: The patients were identified by the French coordinating center for mitochondrial disorders (CARAMMEL), making this a large monocentric series on childhood-onset POLG deficiency. Results: Three patterns of clinical course and survival were observed, distinguished by main category of symptoms: neurologic, hepatic, and gastrointestinal. A total of 24 patients needed urgent neurointensive care for tonic-clonic seizures, myoclonic epilepsy, and status epilepticus, occasionally precipitated by valproate administration. Other neurologic symptoms included dystonia, cerebellar ataxia, and peripheral neuropathy. We report 6 POLG-deficient patients with polyradiculoneuropathy mimicking subacute Guillain-Barré syndrome and provide postgadolinium MRI evidence of diffuse cranial nerve root and cauda equina enhancement, suggesting these disorders have an inflammatory component. Children presenting with enteral nervous system involvement had vomiting, gastroparesis, and chronic intestinal pseudo-obstruction. They had later ages of onset and lived much longer. Primarily, hepatic presentations had the earliest onset and shortest survivals. Secondary hepatic failure was frequently precipitated by valproate administration given before diagnosis to patients with focal impaired awareness seizures or absence of seizures. These POLG deficiencies were often fatal, with age at death ranging from 3 months to 10 years, with a significant difference in survival between the 3 clinical forms; 6 of the 40 children did survive. No genotype-phenotype correlations were found for the 3 clinical course types. Discussion: The study demonstrates the prevalence of neurologic presentation and the extent of central, peripheral, and autonomous nervous system involvement in 60% of patients. Most of the patients with early onset and rapidly fatal hepatic failure did not live long enough to develop neurologic symptoms. The study revealed a new clinical form of POLG deficiency presenting with neurodigestive symptoms with longer lifespan. We also propose that POLG deficiency should be considered in children presenting with unexplained polyradiculoneuropathy, demyelinating neuropathy, and elevated CSF protein. Finally, valproate administration remains a notable cause of avoidable death in POLG-deficient patients.
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Reelin (RELN) is a secreted glycoprotein essential for cerebral cortex development. In humans, recessive RELN variants cause cortical and cerebellar malformations, while heterozygous variants were associated with epilepsy, autism, and mild cortical abnormalities. However, the functional effects of RELN variants remain unknown. We identified inherited and de novo RELN missense variants in heterozygous patients with neuronal migration disorders (NMDs) as diverse as pachygyria and polymicrogyria. We investigated in culture and in the developing mouse cerebral cortex how different variants impacted RELN function. Polymicrogyria-associated variants behaved as gain-of-function, showing an enhanced ability to induce neuronal aggregation, while those linked to pachygyria behaved as loss-of-function, leading to defective neuronal aggregation/migration. The pachygyria-associated de novo heterozygous RELN variants acted as dominant-negative by preventing WT RELN secretion in culture, animal models, and patients, thereby causing dominant NMDs. We demonstrated how mutant RELN proteins in vitro and in vivo predict cortical malformation phenotypes, providing valuable insights into the pathogenesis of such disorders.
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Moléculas de Adhesión Celular Neuronal , Movimiento Celular , Proteínas de la Matriz Extracelular , Mutación Missense , Proteínas del Tejido Nervioso , Proteína Reelina , Serina Endopeptidasas , Humanos , Animales , Proteínas de la Matriz Extracelular/genética , Proteínas de la Matriz Extracelular/metabolismo , Serina Endopeptidasas/genética , Serina Endopeptidasas/metabolismo , Moléculas de Adhesión Celular Neuronal/genética , Moléculas de Adhesión Celular Neuronal/metabolismo , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Ratones , Femenino , Masculino , Movimiento Celular/genética , Neuronas/metabolismo , Neuronas/patología , Polimicrogiria/genética , Polimicrogiria/patología , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Heterocigoto , Lisencefalia/genética , Lisencefalia/patología , AlelosRESUMEN
BACKGROUND: Juvenile Xanthogranuloma (JXG) is a non-Langerhans cell histiocytosis, occurring mainly in infancy. With an extracutaneous lesion, its diagnosis is difficult, because of a wide clinical spectrum. Here we demonstrate and characterize imaging features of 11 patients with JXG of the head and neck in various locations. MATERIAL AND METHODS: We recorded clinical data and reviewed all imaging studies of 11 patients with JXG of the head and neck. Ultrasonography (US) alone was performed in 1 patient; MRI alone in 6 patients; US and MRI in 1 patient; and US, CT, and MRI in 3 patients. We evaluated the following characteristics in all studies: location and number of lesions, echogenicity and vascularization on US, density on CT, signal intensity on T 1 - and T 2 -weighted images, ADC and enhancement on MRI, and tumor boundaries and bone involvement. RESULTS: Lesions were well-defined in 9 cases, and bone erosion was present in 2. On US, lesions were hypoechoic or hyperechoic and with or without vascularization. On CT, lesions were hyper-dense, with no calcification. On MRI, lesions were mildly hyper-intense or iso-intense on T 1 -weighted images in 8 of 9 patients, hypo-intense on T2-weighted images in 7 of 10, low ADC in 7 of 9, and enhancement in 7 of 7. CONCLUSIONS: The diagnosis of extra cutaneous JXG may be proposed, with the following suggestive criteria: age < 1 year, well-defined lesion, mild hyper-intensity on T 1 -weighted images, hypo-intensity on T 2 -weighted images, low ADC, enhancement, and possible adjacent bone involvement.
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Cabeza , Imagen por Resonancia Magnética , Ultrasonografía , Xantogranuloma Juvenil , Humanos , Xantogranuloma Juvenil/diagnóstico por imagen , Xantogranuloma Juvenil/patología , Masculino , Femenino , Preescolar , Lactante , Niño , Imagen por Resonancia Magnética/métodos , Ultrasonografía/métodos , Cabeza/diagnóstico por imagen , Cabeza/patología , Cuello/diagnóstico por imagen , Cuello/patología , Tomografía Computarizada por Rayos X , AdolescenteAsunto(s)
ADN Polimerasa gamma , Imagen por Resonancia Magnética , Mutación , Humanos , ADN Polimerasa gamma/genética , Lactante , Masculino , FemeninoRESUMEN
A 13-year-old boy was admitted with severe meningococcal meningitis. Immunologic workup revealed a properdin deficiency, and genetic sequencing of CFP identified a novel, private and predicted pathogenic variant in exon 8. The patient received broad immunizations and penicillin prophylaxis. Children with invasive meningococcal disease should be tested for complement deficiency.
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Meningitis Meningocócica , Properdina , Humanos , Masculino , Meningitis Meningocócica/diagnóstico , Adolescente , Properdina/deficiencia , Properdina/genética , Neisseria meningitidis/genéticaRESUMEN
Background and Objectives: Hexokinase 1 (encoded by HK1) catalyzes the first step of glycolysis, the adenosine triphosphate-dependent phosphorylation of glucose to glucose-6-phosphate. Monoallelic HK1 variants causing a neurodevelopmental disorder (NDD) have been reported in 12 individuals. Methods: We investigated clinical phenotypes, brain MRIs, and the CSF of 15 previously unpublished individuals with monoallelic HK1 variants and an NDD phenotype. Results: All individuals had recurrent variants likely causing gain-of-function, representing mutational hot spots. Eight individuals (c.1370C>T) had a developmental and epileptic encephalopathy with infantile onset and virtually no development. Of the other 7 individuals (n = 6: c.1334C>T; n = 1: c.1240G>A), 3 adults showed a biphasic course of disease with a mild static encephalopathy since early childhood and an unanticipated progressive deterioration with, e.g., movement disorder, psychiatric disease, and stroke-like episodes, epilepsy, starting in adulthood. Individuals who clinically presented in the first months of life had (near)-normal initial neuroimaging and severe cerebral atrophy during follow-up. In older children and adults, we noted progressive involvement of basal ganglia including Leigh-like MRI patterns and cerebellar atrophy, with remarkable intraindividual variability. The CSF glucose and the CSF/blood glucose ratio were below the 5th percentile of normal in almost all CSF samples, while blood glucose was unremarkable. This biomarker profile resembles glucose transporter type 1 deficiency syndrome; however, in HK1-related NDD, CSF lactate was significantly increased in all patients resulting in a substantially different biomarker profile. Discussion: Genotype-phenotype correlations appear to exist for HK1 variants and can aid in counseling. A CSF biomarker profile with low glucose, low CSF/blood glucose, and high CSF lactate may point toward monoallelic HK1 variants causing an NDD. This can help in variant interpretation and may aid in understanding the pathomechanism. We hypothesize that progressive intoxication and/or ongoing energy deficiency lead to the clinical phenotypes and progressive neuroimaging findings.
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BACKGROUND AND AIMS: Water-soluble vitamins play an essential coenzyme role in the nervous system. Acquired vitamin deficiencies are easily treatable, however, without treatment, they can lead to irreversible complications. This study aimed to provide clinical, laboratory parameters and neuroimaging data on vitamin deficiencies in an attempt to facilitate early diagnosis and prompt supplementation. METHODS: From July 1998 to July 2023, patients at Necker-Enfants-Malades Hospital presenting with acute neurological symptoms attributed to acquired vitamin deficiency were included. Clinical data were extracted from Dr Warehouse database. Neuroimaging, biochemical and electrophysiological data were reviewed. RESULTS: Patients with vitamin B1 deficiency exhibited abnormal eye movements (n = 4/4), fluctuations in consciousness (n = 3/4), and ataxia (n = 3/4). Brain MRI showed alterations of fourth ventricle region (n = 4/4), periaqueductal region (n = 4/4), tectum (n = 3/4), and median thalami (n = 3/4). Patients with vitamin B2 deficiency presented with early onset hypotonia (n = 3/4), hyperlactatemia (n = 4/4), and hyperammonemia (n = 4/4). Plasma acylcarnitines revealed a multiple acyl-coA dehydrogenase deficiency-like profile (n = 4/4). In vitamin B12 deficiency, young children presented with developmental delay (n = 7/7) and older children with proprioceptive ataxia (n = 3/3). Brain MRI revealed atrophy (n = 7/7) and spinal MRI hyperintensity in posterior cervical columns (n = 3/3). Metabolic findings showed elevated methylmalonic acid (n = 6/7) and hyperhomocysteinemia (n = 6/7). Patients with vitamin C deficiency exhibited gait disturbances and muscle weakness (n = 2/2). CONCLUSIONS: Acquired vitamin deficiencies may display reversible clinical symptoms mimicking inherited metabolic disorders. Some situations raise suspicion for diagnosis: concordant clinical presentation, suggestive neuroimaging findings, and/or biochemical evidence. Any acute neurological condition should be treated without waiting for definitive biochemical confirmation.
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Imagen por Resonancia Magnética , Neuroimagen , Humanos , Masculino , Femenino , Preescolar , Neuroimagen/métodos , Lactante , Niño , Avitaminosis/complicaciones , Avitaminosis/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Adolescente , Estudios RetrospectivosRESUMEN
BACKGROUND AND PURPOSE: The characteristics of large vessel occlusion (LVO) in the acute phase of pediatric arterial ischemic stroke and their natural history according to stroke etiology are poorly explored. This studied aimed at describing the prevalence and the radiological evolution of LVO in pediatric AIS. MATERIALS AND METHODS: This single-center retrospective study included consecutive non-neonate children with acute arterial ischemic stroke, intracranial proximal LVO in the anterior circulation (MCA, anterior cerebral artery, and/or ICA), and clinical and imaging follow-up for at least 18 months, during a 9-year period. RESULTS: Intracranial LVO was observed in 24.8% of patients with anterior circulation arterial ischemic stroke and adequate follow-up (n = 26/105), with a median age of 4.2 years (IQR 0.8-9), sex ratio 1.16. The main stroke etiology associated with LVO was unilateral focal cerebral arteriopathy (n = 12, 46%). During follow-up, a specific pattern of unilateral poststroke anastomotic bridge was observed in 8/26 patients, with the poststroke development of nonperforating collaterals forming a bridge in bypass of the LVO site with visible distal flow, within a median delay of 11 months. The development of unilateral poststroke anastomotic bridge was only observed in patients with unilateral focal cerebral arteriopathy. No patient with this pattern experienced stroke recurrence or further progressive vascular modifications. CONCLUSIONS: After stroke, the development of unilateral poststroke anastomotic bridge is specifically observed in children with focal cerebral arteriopathy, appearing in the first year after stroke. This clinical-radiologic pattern was not associated with stroke recurrence or arterial worsening, differentiating it from progressive intracranial arteriopathy, such as Moyamoya angiopathy.
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Isquemia Encefálica , Enfermedades Arteriales Cerebrales , Trastornos Cerebrovasculares , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Niño , Lactante , Preescolar , Estudios Longitudinales , Estudios Retrospectivos , Accidente Cerebrovascular Isquémico/complicaciones , Angiografía Cerebral/métodos , Accidente Cerebrovascular/etiología , Trastornos Cerebrovasculares/complicaciones , Enfermedades Arteriales Cerebrales/complicaciones , Isquemia Encefálica/complicacionesRESUMEN
OBJECTIVE: To describe and compare clinical and microbiological features, surgical and medical management, and outcomes of children with otogenic and sinogenic intracranial empyema (IE) in an institution with an established multidisciplinary protocol. To use the study findings to inform and update the institutional algorithm. METHODS: Retrospective analysis was carried out on the electronic healthcare records of all children with oto-sinogenic IE admitted in a 5-year period. RESULTS: A total of 76 patients were identified and treated according to an institutional protocol. Two distinct groups were identified: intracranial empyema related to otogenic infection (OI-IE, n = 36) or sinogenic infection (SI-IE, n = 40). SI-IE was seen in older children and had a significantly higher morbidity. Sub-dural IE was seen in a minority (n = 16) and only in SI-IE and required urgent collaborative ENT-neurosurgery. Extra-dural IE occurred more frequently and was seen in both SI-IE and OI-IE. No death and overall low morbidity were observed. Particularities found in SI-IE and OI-IE groups (as thrombosis, microbiology, antibiotic treatment, duration and outcome) permitted the delineation of these groups in our updated algorithm. CONCLUSION: The presence of a collaborative multidisciplinary protocol permits the step-wise co-ordination of care for these complex patients in our institution. All patients received prompt imaging, urgent surgical intervention, and antibiotic treatment. Microbiological identification was possible for each patient and antibiotic rationalization was permitted through use of Polymerase chain reaction (PCR) testing in cases of sterile cultures. Of note, intracranial empyema related to sinogenic infection is shown to have significantly more severe clinical presentation, a higher morbidity, and a longer duration of antibiotic therapy than that related to otogenic infection. Study findings allowed for the update and clarification of the institutional protocol, which now clearly demarcates the clinical presentation, biological evidence, radiology, surgical and medical treatments in children with oto-sinogenic IE.
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Absceso Encefálico , Empiema Subdural , Empiema , Niño , Humanos , Empiema Subdural/diagnóstico , Empiema Subdural/epidemiología , Empiema Subdural/etiología , Absceso Encefálico/diagnóstico por imagen , Absceso Encefálico/etiología , Absceso Encefálico/terapia , Estudios Retrospectivos , Antibacterianos/uso terapéuticoRESUMEN
OBJECTIVES: Posterior fossa ependymoma group A (EPN_PFA) and group B (EPN_PFB) can be distinguished by their DNA methylation and give rise to different prognoses. We compared the MRI characteristics of EPN_PFA and EPN_PFB at presentation. METHODS: Preoperative imaging of 68 patients with posterior fossa ependymoma from two centers was reviewed by three independent readers, blinded for histomolecular grouping. Location, tumor extension, tumor volume, hydrocephalus, calcifications, tissue component, enhancement or diffusion signal, and histopathological data (cellular density, calcifications, necrosis, mitoses, vascularization, and microvascular proliferation) were compared between the groups. Categorical data were compared between groups using Fisher's exact tests, and quantitative data using Mann-Whitney tests. We performed a Benjamini-Hochberg correction of the p values to account for multiple tests. RESULTS: Fifty-six patients were categorized as EPN_PFA and 12 as EPN_PFB, with median ages of 2 and 20 years, respectively (p = 0.0008). The median EPN_PFA tumoral volume was larger (57 vs 29 cm3, p = 0.003), with more pronounced hydrocephalus (p = 0.002). EPN_PFA showed an exclusive central position within the 4th ventricle in 61% of patients vs 92% for EPN_PFB (p = 0.01). Intratumor calcifications were found in 93% of EPN_PFA vs 40% of EPN_PFB (p = 0.001). Invasion of the posterior fossa foramina was mostly found for EPN_PFA, particularly the foramina of Luschka (p = 0.0008). EPN_PFA showed whole and homogeneous tumor enhancement in 5% vs 75% of EPN_PFB (p = 0.0008). All mainly cystic tumors were EPN_PFB (p = 0.002). The minimal and maximal relative ADC was slightly lower in EPN_PFA (p = 0.02 and p = 0.01, respectively). CONCLUSION: Morphological characteristics from imaging differ between posterior fossa ependymoma subtypes and may help to distinguish them preoperatively. CLINICAL RELEVANCE STATEMENT: This study provides a tool to differentiate between group A and group B ependymomas, which will ultimately allow the therapeutic strategy to be adapted in the early stages of patient management. KEY POINTS: ⢠Posterior fossa ependymoma subtypes often have different imaging characteristics. ⢠Posterior fossa ependymomas group A are commonly median or lateral tissular calcified masses, with incomplete enhancement, affecting young children and responsible for pronounced hydrocephalus and invasion of the posterior fossa foramina. ⢠Posterior fossa ependymomas group B are commonly median non-calcified masses of adolescents and adults, predominantly cystic, and minimally invasive, with total and homogeneous enhancement.
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Ependimoma , Hidrocefalia , Niño , Adulto , Adolescente , Humanos , Preescolar , Adulto Joven , Imagen por Resonancia Magnética , Pronóstico , Ependimoma/diagnóstico por imagen , Ependimoma/genética , Ependimoma/patología , CabezaRESUMEN
OBJECTIVES: Patients with PMM2-CDG develop acute events (stroke-like episodes (SLEs), thromboses, haemorrhages, seizures, migraines) associated with both clotting factors (factor XI) and coagulation inhibitors (antithrombin, protein C and protein S) deficiencies. The aim of the study was to correlate acute events to haemostasis and propose practical guidelines. METHODS: In this multicentric retrospective study, we evaluated clinical, radiological, haemostasis and electroencephalography data for PMM2-CDG patients hospitalized for acute events. Cerebral events were classified as thrombosis, haemorrhage, SLE, or "stroke mimic" (SM: normal brain imaging or evoking a migraine). RESULTS: Thirteen patients had a total of 31 acute episodes: 27 cerebral events with 7 SLEs, 4 venous thromboses, 4 haemorrhages (3 associated with thrombosis), 15 SMs at a mean age of 7.7 years; 4 non-cerebral thromboses, one of which included bleeding. A trigger was frequently involved (infection, head trauma). Although sometimes normal at baseline state, factor XI, antithrombin and protein C levels decreased during these episodes. No correlation between haemostasis anomalies and type of acute event was found. DISCUSSION: Acute events in PMM2-CDG are not negligible and are associated with haemostasis anomalies. An emergency protocol is proposed for their prevention and treatment (https://www.filiere-g2m.fr/urgences). For cerebral events, brain Magnetic Resonance Imaging with perfusion weight imaging and diffusion sequences, electroencephalogram and haemostasis protein levels guide the treatment: anticoagulation, antithrombin or fresh frozen plasma supplementation, antiepileptic therapy. Preventing bleeding and thrombosis is required in cases of surgery, prolonged immobilization, hormone replacement therapy. CONCLUSION: Acute events in PMM2-CDG are associated with abnormal haemostasis, requiring practical guidance.
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Trastornos Congénitos de Glicosilación , Fosfotransferasas (Fosfomutasas) , Accidente Cerebrovascular , Trombosis , Humanos , Niño , Proteína C , Estudios Retrospectivos , Factor XI , Trastornos Congénitos de Glicosilación/patología , Antitrombinas , Hemostasis , HemorragiaRESUMEN
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.
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OBJECTIVES: Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening condition affecting young children. It is potentially triggered by Epstein-Barr virus (EBV). This study describes the neuroradiological features observed in 75 children with genetically confirmed primary HLH, comparing EBV-induced with non-EBV-induced HLH forms. METHODS: Brain MRIs between 2007 and 2021 from 75 children with HLH according to the 2004 Histiocyte Society criteria and with a confirmed HLH-related mutation, were retrospectively reviewed by two pediatric neuroradiologists blinded to EBV status and to mutation status. At diagnosis, 17 children with EBV viremia above a threshold of 1000 copies/mL were included in the EBV-induced HLH group. The remaining 58 patients were included in the non-EBV-induced HLH group. RESULTS: Of the 75 children initially included, 21 had abnormal MRI (21/75 (28%); 9/17 in the EBV-induced HLH group and 12/58 in the non-EBV-induced HLH group). All patients with abnormal MRI had neurological symptoms. Abnormal MRIs showed white matter lesions; the posterior fossa was affected in all but one case. There was no significant difference between groups regarding the localization or morphology of white matter lesions. The striatum was more frequently affected in the EBV-induced HLH group (8/9 (89%) versus 1/12 (8%), p = 0.00037). All lesions, whether in the white matter or in the basal ganglia, presented increased ADC values on diffusion weighted imaging (DWI). CONCLUSION: In this study of 75 children with genetically confirmed HLH, only children with neurological signs had abnormal brain MRI. Bilateral striatum involvement suggested an EBV-induced form of HLH. KEY POINTS: ⢠In children with genetically proven HLH, only those with neurological signs did have brain abnormalities at MRI. ⢠All patients with abnormal brain MRI had multiple white matter lesions with increased ADC values, including in the posterior fossa in almost all cases. ⢠Basal ganglia and in particular the striatum were bilaterally and symmetrically affected in almost all EBV-induced HLH patients, in contrast to the non-EBV-induced HLH patients.
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Infecciones por Virus de Epstein-Barr , Linfohistiocitosis Hemofagocítica , Niño , Humanos , Preescolar , Herpesvirus Humano 4 , Linfohistiocitosis Hemofagocítica/diagnóstico por imagen , Linfohistiocitosis Hemofagocítica/genética , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/diagnóstico , Estudios Retrospectivos , Cuerpo EstriadoRESUMEN
OBJECTIVE: Distinguishing tumor recurrence from therapy-induced imaging changes (TIIC) on brain MRI in children treated for primary malignant brain tumors may be challenging. The authors aimed to assess the diagnostic ability of multimodal MRI in differentiating TIIC from tumor recurrence. METHODS: The authors retrospectively included children with abnormal supratentorial brain MRI findings after treatment for primary malignant brain tumors (regardless of their localization) with complete resection and radiotherapy. A total of 18 patients with TIIC and 25 patients with tumor recurrence were compared, according to structural, apparent diffusion coefficient (ADC), and arterial spin labeling (ASL) imaging data accrued over time. TIIC were defined by a new MRI scan that was stable for at least 1 year or had regressed, or by histopathology findings in specimens obtained when the anomaly was surgically treated. RESULTS: The time interval between completion of radiotherapy and the appearance of abnormal brain MRI findings was significantly shorter in the TIIC group compared with the tumor recurrence group (median 6 vs 35 months; p < 0.001). TIIC appeared as foci of increased T2-weighted signal intensity, without nodule, associated with variable contrast enhancement. Tumor recurrence appeared as a well-defined nodule with intermediate signal intensity on T2-weighted images with nodular contrast enhancement. Relative ADC values were significantly higher in the TIIC group (median 1.43 vs 0.88; p < 0.001). Relative ASL-cerebral blood flow (CBF) values were significantly lower in the TIIC group (median 0.27 vs 0.43; p = 0.04). On follow-up MRI, TIIC could progress, regress, or remain stable. In most instances (72%), they decreased in size or remained stable at 4 years of follow-up. CONCLUSIONS: MRI features of TIIC include foci of increased signal intensity without a demonstrable nodule on T2-weighted images, high ADC values, and lower ASL-CBF values, whereas tumor recurrence appears as a well-defined nodule with low ADC values and higher ASL-CBF values.
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Neoplasias Encefálicas , Neoplasias Supratentoriales , Humanos , Niño , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirugía , Recurrencia Local de Neoplasia/diagnóstico por imagen , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodos , Imagen de Difusión por Resonancia Magnética/métodos , Neoplasias Supratentoriales/diagnóstico por imagen , Neoplasias Supratentoriales/radioterapia , Neoplasias Supratentoriales/cirugíaRESUMEN
BACKGROUND AND PURPOSE: Stroke-like episodes (SLEs) are defined as acute onset of neurological symptoms mimicking a stroke and radiological lesions non-congruent to vascular territory. We aimed to analyze the acute clinical and radiological features of SLEs to determine their pathophysiology. METHODS: We performed a monocenter retrospective analysis of 120 SLEs in 60 children over a 20-year period. Inclusion criteria were compatible clinical symptoms and stroke-like lesions on brain magnetic resonance imaging (MRI; performed for all 120 events) with focal hyperintensity on diffusion-weighted imaging in a non-vascular territory. RESULTS: Three groups were identified: children with mitochondrial diseases (n = 22) involving mitochondrial DNA mutations (55%) or nuclear DNA mutations (45%); those with other metabolic diseases or epilepsy disorders (n = 22); and those in whom no etiology was found despite extensive investigations (n = 16). Age at first SLE was younger in the group with metabolic or epilepsy disorders (18 months vs. 128 months; p < 0.0001) and an infectious trigger was more frequent (69% vs. 20%; p = 0.0001). Seizures occurred in 75% of episodes, revealing 50% episodes of SLEs and mainly leading to status epilepticus (90%). Of the 120 MRI scans confirming the diagnosis, 28 were performed within a short and strict 48-h period and were further analyzed to better understand the underlying mechanisms. The scans showed primary cortical hyperintensity (n = 28/28) with decreased apparent diffusion coefficient in 52% of cases. Systematic hyperperfusion was found on spin labeling sequences when available (n = 18/18). CONCLUSION: Clinical and radiological results support the existence of a vicious circle based on two main mechanisms: energy deficit and neuronal hyperexcitability at the origin of SLE.
Asunto(s)
Epilepsia , Accidente Cerebrovascular , Niño , Humanos , Lactante , Encéfalo/patología , Epilepsia/complicaciones , Imagen por Resonancia Magnética , Estudios Retrospectivos , Accidente Cerebrovascular/etiología , PreescolarRESUMEN
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
Influenza virus is generally characterized by fever, myalgia, and respiratory symptoms. Neurological entities have already been described, such as acute necrotizing encephalitis (ANE). We aimed to highlight the non-exceptional nature and explore the clinical spectrum and evolution of neurological features related to influenza virus in children. This monocentric observational study included patients under 18 years old, positive for influenza virus, between January 2017 and April 2019 in a pediatric university hospital. Patients were classified into two groups: those with or without a previous significant neurological or metabolic disorder. Two hundred eighty-nine children were identified with influenza infection. Thirty seven had a neurological manifestation: 14 patients who had previous significant neurological or metabolic disorder and 23 patients with no medical history. We identified several clinical patterns: 22 patients had seizures, 7 behavior disorders, 5 disturbances of consciousness, and 3 motor deficits. Four were diagnosed with a known influenza-associated neurological syndrome: 1 ANE, 1 cytotoxic lesion of the corpus callosum, 1 hemiconvulsion-hemiplegia-epilepsia syndrome, and 1 recurrent encephalitis in the context of a RANBP2 mutation. The neurological outcome was favorable in most cases. None of the patients with previous significant disorder retained sequalae or had a recurrence. Two patients had a fatal outcome, and both had a predisposing disorder. CONCLUSION: Various neurological manifestations can be associated with influenza virus. Certain entities led to a poor prognosis, but in most cases, symptoms improved within a few days. The severity of the neurological manifestations correlated with previous neurological or metabolic disorders. WHAT IS KNOWN: ⢠Influenza viruses are well known pathogens with a seasonal epidemic evolution, particularly affecting children. These viruses cause acute fever with respiratory symptoms, associated with myalgia and headaches. Neurological presentation in influenza-virus infection is a well-established possibility as influenza virus is considered to be responsible for 27 to 36% of childhood encephalitis. Some specific and severe entity as acute necrotizing encephalitis, cytotoxic lesion of the corpus callosum, or Hemiconvulsion-hemiplegia-epilepsy syndrome are well described. WHAT IS NEW: ⢠In a French monocentric cohort of 37 children with influenza-related neurologic manifestations, the majority of these manifestations, including seizure, drowsiness, motor deficiency, hallucination are self limiting and do not lead to after-effects. In rare cases (4/37), they may reveal severe encephalitis requiring rapid and appropriate treatment. Otherwise, comparison of a group of 14 children with underlying neurological or metabolic disorder with a group of 23 children free of any significant disorder show that the severity of the neurological manifestations was largely related to previous neurological or metabolic disorders highlighting the importance of vaccination in this population.
Asunto(s)
Encefalitis , Gripe Humana , Leucoencefalitis Hemorrágica Aguda , Orthomyxoviridae , Niño , Humanos , Adolescente , Gripe Humana/complicaciones , Gripe Humana/diagnóstico , Gripe Humana/epidemiología , Estudios Retrospectivos , Leucoencefalitis Hemorrágica Aguda/complicaciones , Hemiplejía/complicaciones , Mialgia/complicaciones , Encefalitis/complicaciones , Encefalitis/diagnóstico , Convulsiones/etiologíaRESUMEN
BACKGROUND: Focal cortical dysplasia (FCD) causes drug-resistant epilepsy in children that can be cured surgically, but the lesions are often unseen by imaging. OBJECTIVE: To assess the efficiency of arterial spin labeling (ASL), voxel-based-morphometry (VBM), fMRI electroencephalography (EEG), resting-state regional homogeneity (ReHo), 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), and their combination in detecting pediatric FCD. METHODS: We prospectively included 10 children for whom FCD was localized by surgical resection. They underwent 3T MR acquisition with concurrent EEG, including ASL perfusion, resting-state BOLD fMRI (allowing the processing of EEG-fMRI and ReHo), 3D T1-weighted images processed using VBM, and FDG PET-CT coregistered with MRI. Detection was assessed visually and by comparison with healthy controls (for ASL and VBM). RESULTS: Eight children had normal MRI, and 2 had asymmetric sulci. Using MR techniques, FCD was accurately detected by ASL for 6/10, VBM for 5/10, EEG-fMRI for 5/8 (excluding 2 with uninterpretable results), and ReHo for 4/10 patients. The combination of ASL, VBM, and ReHo allowed correct FCD detection for 9/10 patients. FDG PET alone showed higher accuracy than the other techniques (7/9), and its combination with VBM allowed correct FCD detection for 8/9 patients. The detection efficiency was better for patients with asymmetric sulci (2/2 for all techniques), but advanced MR techniques and PET were useful for MR-negative patients (7/8). CONCLUSION: A combination of multiple imaging techniques, including PET, ASL, and VBM analysis of T1-weighted images, is effective in detecting subtle FCD in children.