The 2021 World Health Organization Classification of Tumors of the Central Nervous System, Fifth Edition (WHO-CNS5), has strengthened the concept of tumor grade as a combination of histologic ...features and molecular alterations. The WHO-CNS5 tumor type "Diffuse midline glioma, H3K27-altered," classified within the family of "Pediatric-type diffuse high-grade gliomas," incarnates an ideally perfect integrated diagnosis in which location, histology, and genetics clearly define a specific tumor entity. It tries to evenly characterize a group of neoplasms that occur primarily in children and midline structures and that have a dismal prognosis. Such a well-defined pathological categorization has strongly influenced the pediatric oncology community, leading to the uniform treatment of most cases of H3K27-altered diffuse midline gliomas (DMG), based on the simplification that the mutation overrides the histological, radiological, and clinical characteristics of such tumors. Indeed, multiple studies have described pediatric H3K27-altered DMG as incurable tumors. However, in biology and clinical practice, exceptions are frequent and complexity is the rule. First of all, H3K27 mutations have also been found in non-diffuse gliomas. On the other hand, a minority of DMGs are H3K27 wild-type but have a similarly poor prognosis. Furthermore, adult-type tumors may rarely occur in children, and differences in prognosis have emerged between adult and pediatric H3K27-altered DMGs. As well, tumor location can determine differences in the outcome: patients with thalamic and spinal DMG have significantly better survival. Finally, other concomitant molecular alterations in H3K27 gliomas have been shown to influence prognosis. So, when such additional mutations are found, which one should we focus on in order to make the correct clinical decision? Our review of the current literature on pediatric diffuse midline H3K27-altered DMG tries to address such questions. Indeed, H3K27 status has become a fundamental supplement to the histological grading of pediatric gliomas; however, it might not be sufficient alone to exhaustively define the complex biological behavior of DMG in children and might not represent an indication for a unique treatment strategy across all patients, irrespective of age, additional molecular alterations, and tumor location.
Background
Syringomyelia and Chiari malformation are classified as rare diseases on Orphanet, but international guidelines on diagnostic criteria and case definition are missing. Aim of the study: to ...reach a consensus among international experts on controversial issues in diagnosis and treatment of Chiari 1 malformation and syringomyelia in adults.
Methods
A multidisciplinary panel of the Chiari and Syringomyelia Consortium (4 neurosurgeons, 2 neurologists, 1 neuroradiologist, 1 pediatric neurologist) appointed an international Jury of experts to elaborate a consensus document. After an evidence-based review and further discussions, 63 draft statements grouped in 4 domains (definition and classification/planning/surgery/isolated syringomyelia) were formulated. A Jury of 32 experts in the field of diagnosis and treatment of Chiari and syringomyelia and patient representatives were invited to take part in a three-round Delphi process. The Jury received a structured questionnaire containing the 63 statements, each to be voted on a 4-point Likert-type scale and commented. Statements with agreement <75% were revised and entered round 2. Round 3 was face-to-face, during the Chiari Consensus Conference (Milan, November 2019).
Results
Thirty-one out of 32 Jury members (6 neurologists, 4 neuroradiologists, 19 neurosurgeons, and 2 patient association representatives) participated in the consensus. After round 2, a consensus was reached on 57/63 statements (90.5%). The six difficult statements were revised and voted in round 3, and the whole set of statements was further discussed and approved.
Conclusions
The consensus document consists of 63 statements which benefited from expert discussion and fine-tuning, serving clinicians and researchers following adults with Chiari and syringomyelia.
In anticipation of the “Chiari and Syringomyelia Consensus Conference” held in Milan in 2019, we performed a systematic literature review on the management of Chiari malformation type 1 (CM1) and ...syringomyelia (Syr) in children.
We aimed to summarize the available evidence and identify areas where consensus has not been reached and further research is needed.
In accordance with PRISMA guidelines, we formulated seven questions in Patients-Interventions-Comparators-Outcomes (PICO) format. Six PICOs concerned CM1 children with/without additional structural anomalies (Syr, craniosynostosis, hydrocephalus, tethered cord, and cranio-vertebral junction anomalies), and one PICO Syr without CM1. We searched Medline, Embase, Cochrane, and NICE databases from January 1, 1999, to May 29, 2019. Cohort studies, controlled and randomized clinical trials (CCTs, RCTs), and systematic reviews were included, all pertinent only to patients ≤ 18 years of age.
For CM1, 3787 records were found, 460 full texts were assessed and 49 studies (46 cohort studies, one RCT, and two systematic reviews) were finally included. For Syr, 376 records were found, 59 full texts were assessed, and five studies (one RCT and four cohort studies) were included. Data on each PICO were synthetized narratively due to heterogeneity in the inclusion criteria, outcome measures, and length of follow-up of the included studies.
Despite decades of experience on CM1 and Syr management in children, the available evidence remains limited. Specifically, there is an urgent need for collaborative initiatives focusing on the adoption of shared inclusion criteria and outcome measures, as well as rigorous prospective designs, particularly RCTs.
Background
Chiari malformation type 1 (CM1) is a rare condition where agreed classification and treatment are still missing. The goal of this study is to achieve a consensus on the diagnosis and ...treatment of CM1 in children.
Methods
A multidisciplinary panel formulated 57 provisional statements based on a review of the literature. Thirty-four international experts (IE) participated in a Delphi study by independently rating each statement on a 4-point Likert scale (“strongly disagree,” “disagree,” “agree,” “strongly agree”). Statements that were endorsed (“agree” or “strongly agree”) by < 75% of raters were re-formulated, or new statements were added, and another Delphi round followed (up to a maximum of three).
Results
Thirty-five IE were contacted and 34 agreed to participate. A consensus was reached on 30/57 statements (52.6%) after round 1. Three statements were added, and one removed. After round 2, agreement was reached on 56/59 statements (94.9%). Finally, after round 3, which took place during the 2019 Chiari Consensus Conference (Milan, Italy), agreement was reached on 58/59 statements (98.3%) about four main sections (Definition and Classification, Planning, Surgery, Isolated Syringomyelia). Only one statement did not gain a consensus, which is the “definition of radiological failure 24 month post-surgery.”
Conclusions
The consensus document consists of 58 statements (24 on diagnosis, 34 on treatment), serving clinicians and researchers following children with CM1. There is a clear need for establishing an international network and registry and to promote collaborative studies to increase the evidence base and optimize the long-term care of this patient population.
Children and adolescents affected by brain tumors are at risk for neuropsychological sequelae that need to be evaluated in order to plan adequate rehabilitation programs, and to support their ...development and recovery. This work aims to describe an innovative prospective observational study protocol for the early evaluation and monitoring over time of neuropsychological outcomes in this pediatric population. Pediatric patients aged 3-17 with a brain tumor diagnosis will be assessed through the use of a battery of Italian standardized neuropsychological tests, with good psychometric properties and age-appropiate, at three different time points of their clinical course: at diagnosis and before surgery (T0), after surgical removal and before the start of potential adjuvant therapies (T1), and at the one-year follow-up after potential adjuvant therapies (T2). This study will allow clinicians to support the neuropsychological development of these children by promoting appropriate and timely rehabilitation and educational programs from the early phases of their clinical course.
Neuroendoscopic surgery is being used as an alternative to traditional shunt surgery and craniotomy in the management of hydrocephalus and intracranial fluid-filled cavities. In this study, the ...authors evaluated the incidence and type of complications occurring after neuroendoscopic procedures that were performed in a consecutive series of pediatric patients at a single institution to determine the effectiveness of neuroendoscopy in such patients.
Four hundred ninety-five neuroendoscopic procedures were consecutively performed in 450 pediatric patients at one institution over a 10-year period. Charts were retrospectively reviewed. A complication was defined as follows: 1) any postoperative neurological deficit that was not observed before surgery; 2) any event occurring during surgery that resulted in the procedure being aborted; or 3) any adverse event occurring within 7 days postsurgery that resulted in a modification of the normal postoperative care. However, headache, vomiting, and fever without cerebrospinal fluid (CSF) pleocytosis were not considered complications. Complications were observed in 40 (8.1%) of 495 procedures. Two patients had two complications. One patient died of diffuse brain edema following endoscopic biopsy sampling of a basal ganglia tumor (mortality rate 0.2%). Other complications observed were abandonment of the procedure in eight cases, CSF leakage in 11 (with associated wound infection in one), intraventricular hemorrhage in six (with external drainage needed in four), intraparenchymal hemorrhage in three, subdural collection in eight (with subdural-peritoneal shunt placement needed in seven), transient oculomotor palsy in two, and transient hemiparesis in one.
Many complications can be avoided by determining the correct diagnosis and using suitable techniques and instruments. Most complications can be managed conservatively and do not produce long-term morbidity. Complex procedures in most patients and simple procedures in patients with preoperative risk factors carry the highest hazard. Every attempt should be made to optimize the surgical technique. The most serious and potentially the most lethal complication remains arterial bleeding from injury to the basilar artery complex.
Purpose
The combined recordings of epidural-(D wave) and muscle motor evoked potentials (m-MEPs) have been proposed in many studies in intramedullary spinal cord tumour (IMSCT) surgery, although not ...all agree. Furthermore, the usefulness of the intraoperative monitoring of motor systems using these methods in other types of spine surgery has not yet been clearly confirmed. The aim of this study is to test the impact of intraoperative D wave on the monitorability and motor outcome in spine surgery.
Methods
Intraoperative recording of posterior tibial nerve somatosensory potentials, lower limb m-MEPs (LLm-MEPs) and epidurally recorded D wave caudally to the surgical level was attempted in a total of 103 spine and spinal cord surgeries (23 IMSCT, 55 extramedullary spinal cord tumours and 25 myelopathies).
Results
There was a 97.1 %, overall monitorability where at least 1 of the 3 modalities was applicable in 100 surgical procedures. Baseline LLm-MEPs were recorded bilaterally in 85 cases and unilaterally in 11. A caudal D wave was recorded in 97 cases. Transient, or persistent intraoperative modifications occurred in 14/23 IMSCT, 5/55 extramedullary spinal cord tumours and in 2/25 myelopathies. The presence of a persistent stable caudal D wave was predictive of a good motor outcome even when the LL-MEPs were absent and/or when lost during surgery.
Conclusions
Not only is intraoperative D wave recording to be considered mandatory in IMSCT surgery but it should also be attempted in other types of spine/spinal cord surgeries.
Abstract Objective To assess the audiological profile in a cohort of children affected by syndromic craniosynostosis. Methods Eleven children with Apert syndrome (n = 4), Saethre-Chotzen syndrome (n ...= 3), Muenke syndrome (n = 2), Crouzon syndrome (n = 1) and Pfeiffer syndrome type 1 (n = 1) were submitted to a complete audiologic evaluation including otoscopy, pure-tone audiometry, tympanometry and acoustic reflex testing, ABR, otoacustic emissions, temporal bone High Resolution CT (HRCT) scan. The main outcome measures were prevalence, type and severity of hearing loss, prevalence of chronic otitis media, correlation with the time of first surgical correction. Results Seven of 11 patients (64%) presented hearing loss (HL), conductive in 3/7 patients (43%) and mixed in 4/7 (57%). No patients showed a purely sensorineural HL. All hearing impaired patients displayed middle ear disorders: the patients with conductive HL had otitis media with effusion (OME) and 3/4 patients with mixed HL showed tympanic alterations or cholesteatoma. A bilateral vestibular aqueduct enlargement was detected by HRCT scan in one normal hearing patient. The ABRs resulted normal in all cases. Conclusion Our study confirms the high prevalence of otologic diseases in such patients. In contrast with previous studies, middle ear disorders were responsible for the hearing impairment also in patients with mixed HL due to secondary inner ear damage. These findings restate the necessity of a close audiologic follow-up. We did not detect the specific ABR abnormalities previously reported, possibly because of an early correction of the cranial vault malformations.
Abstract
BACKGROUND: CNS embryonal tumors are a clinically and biologically heterogeneous group of tumors, more frequently arising in very young children. In the last few years, tumor classification ...through DNA methylation profiling has been demonstrated to be a powerful diagnostic tool which could be especially informative in this setting. METHODS: We reviewed original diagnosis and molecular profile of childhood CNS embryonal tumors other than medulloblastoma or AT/RT from a retrospective single-center cohort. Sixteen FFPE tissue samples from 14 unique patients (diagnosed from 1996 to 2017) were analyzed using DNA methylation arrays and matched with the Heidelberg classifier. Then, cohort characteristics and outcome were re-evaluated according to the results of the array. RESULTS: Median age at diagnosis was 2.7 years; there was no statistically significant difference between ETMRs and CNS embryonal tumors, NOS. Male to female ratio was 4:3. Median OS was 17,5 months (IQR 10.2-103.3 months) and ETMRs presented the worst outcome. Methylation profiling matched with an adequate score in 50% of samples (8/16). DNA methylation profile was consistent with ETMR in two samples but only one showed amplification of C19MC. Seven CNS embryonal tumors, NOS were properly reclassified as supratentorial ependymoma and diffuse pediatric-type HGG (4 and 1) or better defined as CNS neuroblastoma, FOXR2-altered (2). Methylation profiling added a unique diagnostic contribution in 64.3% of all cases (9/14). After the integration of methylation array results, survival markedly differed according to the novel integrated diagnoses; supratentorial ependymomas presented the longest median OS while no patients refined as CNS neuroblastoma or HGG survived. CONCLUSIONS: Our study confirmed that DNA methylation profiling provides relevant information for the classification of rare neoplasms like CNS embryonal tumors. Especially for selected cases with ambiguous histology, implementation of this tool should be considered to improve diagnostic precision and tailor patients’ management.
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