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Clinical Neurology and Neurosurgery Jul 2024Cerebellar mutism syndrome (CMS) is a serious complication of posterior fossa surgeries affecting mainly pediatric age group. The pathophysiology is still not fully... (Review)
Review
INTRODUCTION
Cerebellar mutism syndrome (CMS) is a serious complication of posterior fossa surgeries affecting mainly pediatric age group. The pathophysiology is still not fully understood. It adversely affects the recovery of patients. There is no definitive and standardized management for CMS. However pharmacological therapy has been used in reported cases with variable effectiveness. We aim through this review to summarize the available evidence on pharmacological agents used to treat CMS.
METHOD
A thorough systematic review until December 2022, was conducted using PubMed Central, Embase, and Web of Science, databases to identify case reports and case series of CMS patients who underwent posterior fossa surgery and received pharmacological treatment. Patients with pathologies other than posterior fossa lesions were excluded from the study.
RESULTS
Of 592 initial studies, 8 studies met our eligibility criteria for inclusion, with 3 more studies were added through manual search; reporting on 13 patients. The median age of 13 years (Standard deviation SD=10.60). The most frequent agent used was Bromocriptine. Other agents were fluoxetine, midazolam, zolpidem, and arpiprazole. Most patients recovered within 48 hours of initiating medical therapy. The median follow-up period was 4 months (SD=13.8). All patients showed complete recovery at the end of follow-up period.
CONCLUSION
Cerebellar mutism syndrome is reported after posterior fossa surgeries, despite attempts to identify risk factors, pathophysiology, and management of CMS, it remains a challenging condition with significant morbidity. Different Pharmacological treatments have been proposed with promising results. Further studies and formalized clinical trials are needed to evaluate available options and their effectiveness.
Topics: Humans; Mutism; Neurosurgical Procedures; Postoperative Complications; Cranial Fossa, Posterior; Cerebellar Diseases; Child; Adolescent
PubMed: 38823197
DOI: 10.1016/j.clineuro.2024.108352 -
Child's Nervous System : ChNS :... Jul 2024To ascertain the presence of catatonia in cases of pediatric postoperative cerebellar mutism syndrome (PPCMS). (Review)
Review
OBJECTIVE
To ascertain the presence of catatonia in cases of pediatric postoperative cerebellar mutism syndrome (PPCMS).
METHOD
A systematic review of PPCMS case reports of patients aged 0-17 years with sufficient clinical information to extract catatonic phenomena was undertaken following PRISMA guidelines. Standardized catatonia rating scales were applied to selected cases retrospectively to ascertain whether diagnostic criteria for catatonia were met. A case known to the authors is also presented.
RESULTS
Two hundred twenty-one suitable full-text articles were identified. Following screening and application of inclusion criteria, 51 articles were selected plus seven more from their references, reporting on 119 subjects. All cases met Bush and Francis (BF) diagnostic criteria for catatonia, 92.5% Pediatric Catatonia Rating Scale (PCRS), 52.9% ICD-11, and 44.5% DSM-5. All patients presented with mutism. The next most frequent signs were immobility/stupor (77.3%), withdrawal (35.3%), mannerisms (23.5%), and excitement/agitation (18.5%). Most cases presented with stuporous catatonia (75.6%). Catatonia most frequently occurred following resection of medulloblastoma (64.7%). Preoperative hydrocephalus occurred in 89 patients (74.8%).
CONCLUSION
Catatonia was frequent in this PPCMS sample, with a predominant stuporous variant; it should be considered in patients with PPCMS and assessed with reliable and validated instruments for prompt diagnosis and management.
Topics: Adolescent; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Catatonia; Cerebellar Diseases; Mutism; Postoperative Complications
PubMed: 38630268
DOI: 10.1007/s00381-024-06392-x -
Journal of Neurosurgery. Pediatrics Jun 2024Brain tumors are a global problem, leading to higher cancer-related morbidity and mortality rates in children. Despite the progressive though slow advances in... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Brain tumors are a global problem, leading to higher cancer-related morbidity and mortality rates in children. Despite the progressive though slow advances in neuro-oncology care, research, and diagnostics in sub-Saharan Africa (SSA), the epidemiological landscape of pediatric brain tumors (PBTs) remains underestimated. This study aimed to systematically analyze the distribution of PBT types in SSA.
METHODS
Ovid Medline, Global Index Medicus, African Journals Online, Google Scholar, and faculty of medicine libraries were searched for literature on PBTs in SSA published before October 29, 2022. A proportional meta-analysis was performed.
RESULTS
Forty-nine studies, involving 2360 children, met the inclusion criteria for review; only 20 (40.82%) were included in the quantitative analysis. South Africa and Nigeria were the countries with the most abundant data. Glioma not otherwise specified (NOS) was the common PBT in the 4 SSA regions combined. However, medulloblastoma was more commonly reported in Southern SSA (p = 0.01) than in other regions. The prevalence and the overall pooled proportion of the 3 common PBTs was estimated at 46.27% and 0.41 (95% CI 0.32-0.50, 95% prediction interval [PI] 0.11-0.79), 25.34% and 0.18 (95% CI 0.14-0.21, 95% PI 0.06-0.40), and 12.67% and 0.12 (95% CI 0.09-0.15, 95% PI 0.04-0.29) for glioma NOS, medulloblastoma, and craniopharyngioma, respectively. Sample size moderated the estimated proportion of glioma NOS (p = 0.02). The highest proportion of craniopharyngiomas was in Western SSA, and medulloblastoma and glioma NOS in Central SSA.
CONCLUSIONS
These findings provide insight into the trends of PBT types and the proportion of the top 3 most common tumors across SSA. Although statistical conclusions are difficult due to the inconsistency in the data, the study identifies critical areas for policy development and collaborations that can facilitate improved outcomes in PBTs in SSA. More accurate epidemiological studies of these tumors are needed to better understand the burden of the disease and the geographic variation in their distribution, and to raise awareness in their subsequent management.
Topics: Humans; Brain Neoplasms; Africa South of the Sahara; Child; Glioma; Child, Preschool; Adolescent; Prevalence; Medulloblastoma; Craniopharyngioma; Infant
PubMed: 38489811
DOI: 10.3171/2024.1.PEDS23282 -
Fluids and Barriers of the CNS Feb 2024The cerebrospinal fluid (CSF) proteome could offer important insights into central nervous system (CNS) malignancies. To advance proteomic research in pediatric CNS... (Meta-Analysis)
Meta-Analysis Review
Mass spectrometry-based proteomics of cerebrospinal fluid in pediatric central nervous system malignancies: a systematic review with meta-analysis of individual patient data.
BACKGROUND
The cerebrospinal fluid (CSF) proteome could offer important insights into central nervous system (CNS) malignancies. To advance proteomic research in pediatric CNS cancer, the current study aims to (1) evaluate past mass spectrometry-based workflows and (2) synthesize previous CSF proteomic data, focusing on both qualitative summaries and quantitative re-analysis. MAIN: In our analysis of 11 studies investigating the CSF proteome in pediatric patients with acute lymphoblastic leukemia (ALL) or primary brain tumors, we observed significant methodological variability. This variability negatively affects comparative analysis of the included studies, as per GRADE criteria for quality of evidence. The qualitative summaries covered 161 patients and 134 non-tumor controls, while the application of validation cohort varied among the studies. The quantitative re-analysis comprised 15 B-ALL vs 6 "healthy" controls and 15 medulloblastoma patients vs 22 non-tumor controls. Certain CSF proteins were identified as potential indicators of specific malignancies or stages of neurotoxicity during chemotherapy, yet definitive conclusions were impeded by inconsistent data. There were no proteins with statistically significant differences when comparing cases versus controls that were corroborated across studies where quantitative reanalysis was feasible. From a gene ontology enrichment, we observed that age disparities between unmatched case and controls may mislead to protein correlations more indicative of age-related CNS developmental stages rather than neuro-oncological disease. Despite efforts to batch correct (HarmonizR) and impute missing values, merging of dataset proved unfeasible and thereby limited meaningful data integration across different studies.
CONCLUSION
Infrequent publications on rare pediatric cancer entities, which often involve small sample sizes, are inherently prone to result in heterogeneous studies-particularly when conducted within a rapidly evolving field like proteomics. As a result, obtaining clear evidence, such as CSF proteome biomarkers for CNS dissemination or early-stage neurotoxicity, is currently impractical. Our general recommendations comprise the need for standardized methodologies, collaborative efforts, and improved data sharing in pediatric CNS malignancy research. We specifically emphasize the possible importance of considering natural age-related variations in CSF due to different CNS development stages when matching cases and controls in future studies.
Topics: Child; Humans; Proteome; Proteomics; Central Nervous System Neoplasms; Mass Spectrometry; Biomarkers; Cerebrospinal Fluid
PubMed: 38350915
DOI: 10.1186/s12987-024-00515-x -
International Journal of Radiation... Jun 2024Radiation myelitis (RM) is a rare complication of radiation therapy (RT). The Pediatric Normal Tissue Effects in the Clinic spinal cord task force aimed to identify RT... (Review)
Review
PURPOSE
Radiation myelitis (RM) is a rare complication of radiation therapy (RT). The Pediatric Normal Tissue Effects in the Clinic spinal cord task force aimed to identify RT dose effects and assess risk factors for RM in children. Through systematic review, we analyzed RT dose, fraction size, latency between completion of RT and toxicity, chemotherapy use, age when irradiated, and sex.
METHODS AND MATERIALS
We conducted literature searches of peer-reviewed manuscripts published from 1964 to June 2017 evaluating RM among children. Normality of variables was assessed with Kolmogorov-Smirnov or Shapiro-Wilk tests. Spearman's rank correlation coefficients were used to test correlations between RT dose/fraction size and latency between RT and development of toxicity.
RESULTS
Of 1329 identified and screened reports, 144 reports were fully reviewed and determined to have adequate data for analysis; 16 of these reports had a total of 33 cases of RM with a median age of 13 years (range, 0.2-18) at the time of RT. The most common primary tumor histologies were rhabdomyosarcoma (n = 9), medulloblastoma (n = 5), and Hodgkin lymphoma (n = 2); the most common chemotherapy agents given were vincristine (n = 15), intrathecal methotrexate (n = 12), and intrathecal cytarabine (n = 10). The median RT dose and fraction size were 40 Gy (range, 24-57.4 Gy) and 1.8 Gy (range, 1.3-2.6 Gy), respectively. RT dose resulting in RM in patients who also received chemotherapy was lower than in those not receiving chemotherapy (mean 39.6 vs 49.7 Gy; P = .04). There was no association of age with RT dose. The median latency period was 7 months (range, 1-29). Higher RT dose was correlated with longer latency periods (P = .03) to RM whereas sex, age, fraction size, and chemotherapy use were not. Two of 17 patients with adequate follow-up recovered from RM; unfortunately, it was fatal in 6 of 15 evaluable patients. Complication probability modeling was not possible because of the rarity of events.
CONCLUSIONS
This report demonstrates a relatively short latency from RT (with or without chemotherapy) to RM and a wide range of doses (including fraction sizes) associated with RM. No apparent association with age at the time of RT could be discerned. Chemotherapy appears to reduce spinal cord tolerance. Recovery from RM is rare, and it is often fatal.
Topics: Humans; Child; Adolescent; Child, Preschool; Male; Infant; Radiation Injuries; Female; Neoplasms; Radiotherapy Dosage; Myelitis; Medulloblastoma; Risk Factors; Rhabdomyosarcoma; Hodgkin Disease; Age Factors; Spinal Cord Diseases
PubMed: 38323945
DOI: 10.1016/j.ijrobp.2023.12.020 -
International Journal of Radiation... Jun 2024Reirradiation is increasingly used in children and adolescents/young adults (AYA) with recurrent primary central nervous system tumors. The Pediatric Normal Tissue... (Review)
Review
PURPOSE
Reirradiation is increasingly used in children and adolescents/young adults (AYA) with recurrent primary central nervous system tumors. The Pediatric Normal Tissue Effects in the Clinic (PENTEC) reirradiation task force aimed to quantify risks of brain and brain stem necrosis after reirradiation.
METHODS AND MATERIALS
A systematic literature search using the PubMed and Cochrane databases for peer-reviewed articles from 1975 to 2021 identified 92 studies on reirradiation for recurrent tumors in children/AYA. Seventeen studies representing 449 patients who reported brain and brain stem necrosis after reirradiation contained sufficient data for analysis. While all 17 studies described techniques and doses used for reirradiation, they lacked essential details on clinically significant dose-volume metrics necessary for dose-response modeling on late effects. We, therefore, estimated incidences of necrosis with an exact 95% CI and qualitatively described data. Results from multiple studies were pooled by taking the weighted average of the reported crude rates from individual studies.
RESULTS
Treated cancers included ependymoma (n = 279 patients; 7 studies), medulloblastoma (n = 98 patients; 6 studies), any CNS tumors (n = 62 patients; 3 studies), and supratentorial high-grade gliomas (n = 10 patients; 1 study). The median interval between initial and reirradiation was 2.3 years (range, 1.2-4.75 years). The median cumulative prescription dose in equivalent dose in 2-Gy fractions (EQD2; assuming α/β value = 2 Gy) was 103.8 Gy (range, 55.8-141.3 Gy). Among 449 reirradiated children/AYA, 22 (4.9%; 95% CI, 3.1%-7.3%) developed brain necrosis and 14 (3.1%; 95% CI, 1.7%-5.2%) developed brain stem necrosis with a weighted median follow-up of 1.6 years (range, 0.5-7.4 years). The median cumulative prescription EQD2 was 111.4 Gy (range, 55.8-141.3 Gy) for development of any necrosis, 107.7 Gy (range, 55.8-141.3 Gy) for brain necrosis, and 112.1 Gy (range, 100.2-117 Gy) for brain stem necrosis. The median latent period between reirradiation and the development of necrosis was 5.7 months (range, 4.3-24 months). Though there were more events among children/AYA undergoing hypofractionated versus conventionally fractionated reirradiation, the differences were not statistically significant (P = .46).
CONCLUSIONS
Existing reports suggest that in children/AYA with recurrent brain tumors, reirradiation with a total EQD2 of about 112 Gy is associated with an approximate 5% to 7% incidence of brain/brain stem necrosis after a median follow-up of 1.6 years (with the initial course of radiation therapy being given with conventional prescription doses of ≤2 Gy per fraction and the second course with variable fractionations). We recommend a uniform approach for reporting dosimetric endpoints to derive robust predictive models of late toxicities following reirradiation.
Topics: Humans; Re-Irradiation; Necrosis; Child; Neoplasm Recurrence, Local; Central Nervous System Neoplasms; Adolescent; Brain; Brain Stem; Ependymoma; Young Adult; Child, Preschool; Medulloblastoma; Radiation Injuries
PubMed: 38300187
DOI: 10.1016/j.ijrobp.2023.12.043 -
Journal of Neuro-oncology Mar 2024Central nervous system (CNS) tumours account for around 25% of childhood neoplasms. With multi-modal therapy, 5-year survival is at around 75% in the UK. Conventional... (Review)
Review
BACKGROUND
Central nervous system (CNS) tumours account for around 25% of childhood neoplasms. With multi-modal therapy, 5-year survival is at around 75% in the UK. Conventional photon radiotherapy has made significant contributions to survival, but can be associated with long-term side effects. Proton beam radiotherapy (PBT) reduces the volume of irradiated tissue outside the tumour target volume which may potentially reduce toxicity. Our aim was to assess the effectiveness and safety of PBT and make recommendations for future research for this evolving treatment.
METHODS
A systematic review assessing the effects of PBT for treating CNS tumours in children/young adults was undertaken using methods recommended by Cochrane and reported using PRISMA guidelines. Any study design was included where clinical and toxicity outcomes were reported. Searches were to May 2021, with a narrative synthesis employed.
RESULTS
Thirty-one case series studies involving 1731 patients from 10 PBT centres were included. Eleven studies involved children with medulloblastoma / primitive neuroectodermal tumours (n = 712), five ependymoma (n = 398), four atypical teratoid/rhabdoid tumour (n = 72), six craniopharyngioma (n = 272), three low-grade gliomas (n = 233), one germ cell tumours (n = 22) and one pineoblastoma (n = 22). Clinical outcomes were the most frequently reported with overall survival values ranging from 100 to 28% depending on the tumour type. Endocrine outcomes were the most frequently reported toxicity outcomes with quality of life the least reported.
CONCLUSIONS
This review highlights areas of uncertainty in this research area. A well-defined, well-funded research agenda is needed to best maximise the potential of PBT.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO-CRD42016036802.
Topics: Child; Humans; Young Adult; Proton Therapy; Quality of Life; Central Nervous System Neoplasms; Central Nervous System; Pituitary Neoplasms; Cerebellar Neoplasms
PubMed: 38294638
DOI: 10.1007/s11060-023-04510-4 -
World Neurosurgery Mar 2024Maximizing surgical resection of medulloblastoma (MB) affects overall survival; nevertheless, surgical resection remains a because of the infiltrative behavior of this...
The Application of Sodium Fluorescein in Resection of Medulloblastoma Under YELLOW 560 Filter: Feasibility and Preliminary Results of a Monocentric Cohort and Systematic Review.
BACKGROUND
Maximizing surgical resection of medulloblastoma (MB) affects overall survival; nevertheless, surgical resection remains a because of the infiltrative behavior of this tumor. Several dyes have been tested for improving tumor visualization; however, few reports with different protocols of fluorophores use are available and the results are inconsistent. Hence, we report our experience with sodium fluorescein in MB surgery, aiming to assess the role of this technique on the extent of resection. Furthermore, we performed a literature review of this topic.
METHODS
Fluorescence characteristics, extent of resection, and clinical outcome were analyzed in 9 consecutively operated patients with MB. A comprehensive literature search and review for English-language articles concerning fluorescein application in MB was conducted.
RESULTS
In our cohort, no side effect related to fluorescein occurred; all tumors presented with an intense or moderate yellow-green enhancement, and fluorescein was judged fundamental in distinguishing tumors from viable tissue in 7 of 9 cases. Gross total resection or near-total resection (i.e., a residual tumor volume <1.5 cm) was achieved in 8 patients. The review explored the different techniques and surgical interpretations as well as surgical radicality; we did not find a homogenous protocol for fluorescein injection in the published articles. Fluorescence appeared moderate or intense in almost all cases, with a high percentage of usefulness and consensual achievement of a high rate of gross total resection.
CONCLUSIONS
Based on these results, we can infer that fluorescein-guided surgical resection is a safe and valuable method for patients with MB.
Topics: Humans; Fluorescein; Medulloblastoma; Feasibility Studies; Brain Neoplasms; Neurosurgical Procedures; Fluorescent Dyes; Cerebellar Neoplasms
PubMed: 38154682
DOI: 10.1016/j.wneu.2023.12.105 -
Cancers Sep 2023Medulloblastoma (MB) is the most common malignant brain tumor in childhood. Although recent multi-omic studies have led to advances in MB classification, there is still... (Review)
Review
Medulloblastoma (MB) is the most common malignant brain tumor in childhood. Although recent multi-omic studies have led to advances in MB classification, there is still room for improvement with regard to treatment response and survival. Therefore, identification of new and less invasive biomarkers is needed to refine the diagnostic process and to develop more personalized treatment strategies. In this context, non-coding RNAs (ncRNAs) could be useful biomarkers for MB. In this article, we reviewed the role of two types of ncRNAs, long non-coding (lncRNAs) and circular RNAs (circRNAs), as biomarkers for the diagnosis, subgroup classification, and prognosis of MB. We also reviewed potential candidates with specific functions and mechanisms of action in the disease. We performed a search in PubMed and Scopus using the terms ("long non coding RNAs" OR "lncRNAs") and ("circular RNAs" OR "circRNAs") AND "medulloblastoma" to identify biomarker discovery or functional studies evaluating the effects of these ncRNAs in MB. A total of 26 articles met the inclusion criteria. Among the lncRNAs, the tumorigenic effects of the upregulated and were the most studied in MB. Among the circRNAs, the upregulation of and its functional impact in MB cell lines were the most consistent results, so this circRNA could be considered a potential biomarker in MB. Additional validation is required for many deregulated lncRNAs and circRNAs; therefore, further studies are warranted.
PubMed: 37835380
DOI: 10.3390/cancers15194686 -
Advances in Radiation Oncology 2023[This corrects the article DOI: 10.1016/j.adro.2023.101189.].
Erratum to: Young S, Phaterpekar K, Tsang DS, Boldt G, Bauman GS. Proton Radiotherapy for Management of Medulloblastoma: A Systematic Review of Clinical Outcomes. 2023;8:101189.
[This corrects the article DOI: 10.1016/j.adro.2023.101189.].
PubMed: 37465005
DOI: 10.1016/j.adro.2023.101232