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Acta Neuropathologica Communications Jul 2023Trimethylation of lysine 27 on histone 3 (H3K27me3) loss has been implicated in worse prognoses for patients with meningiomas. However, there have been challenges in... (Meta-Analysis)
Meta-Analysis Review
Trimethylation of lysine 27 on histone 3 (H3K27me3) loss has been implicated in worse prognoses for patients with meningiomas. However, there have been challenges in measuring H3K27me3 loss, quantifying its impact, and interpreting its clinical utility. We conducted a systematic review across Pubmed, Embase, and Web of Science to identify studies examining H3K27me3 loss in meningioma. Clinical, histopathological, and immunohistochemistry (IHC) characteristics were aggregated. A meta-analysis was performed using a random-effects model to assess prevalence of H3K27me3 loss and meningioma recurrence risk. Study bias was characterized using the NIH Quality Assessment Tool and funnel plots. Nine publications met inclusion criteria with a total of 2376 meningioma cases. The prevalence of H3K27me3 loss was 16% (95% CI 0.09-0.27), with higher grade tumors associated with a significantly greater proportion of loss. H3K27me3 loss was more common in patients who were male, had recurrent meningiomas, or required adjuvant radiation therapy. Patients were 1.70 times more likely to have tumor recurrence with H3K27me3 loss (95% CI 1.35-2.15). The prevalence of H3K27me3 loss in WHO grade 2 and 3 meningiomas was found to be significantly greater in tissue samples less than five years old versus tissue of all ages and when a broader definition of IHC staining loss was applied. This analysis demonstrates that H3K27me3 loss significantly associates with more aggressive meningiomas. While differences in IHC and tumor tissue age have led to heterogeneity in studying H3K27me3 loss, a robust prognostic signal is present. Our findings suggest an opportunity to improve study design and standardize tissue processing to optimize clinical viability of this epigenetic marker.
Topics: Child, Preschool; Female; Humans; Male; Biomarkers, Tumor; Histones; Meningeal Neoplasms; Meningioma; Prognosis
PubMed: 37491289
DOI: 10.1186/s40478-023-01615-9 -
Tropical Medicine and Infectious Disease Sep 2022West Nile virus (WNV) is a mosquito-borne flavivirus that has emerged as a major cause of viral encephalitis and meningitis, rarely leading to death. Several risk... (Review)
Review
West Nile virus (WNV) is a mosquito-borne flavivirus that has emerged as a major cause of viral encephalitis and meningitis, rarely leading to death. Several risk factors have been discussed in the past concerning the severity of the disease, while few reports have focused on precipitating conditions that determine of WNV-related death. Studies on cohorts of patients suffering of West Nile disease (WND) usually encompass low numbers of deceased patients as a result of the rarity of the event. In this systematic review and critical analysis of 428 published case studies and case series, we sought to evaluate and highlight critical parameters of WND-related death. We summarized the symptoms, comorbidities, and treatment strategies related to WND in all published cases of patients that included clinical features. Symptoms such as altered mental status and renal problems presented increased incidence among deceased patients, while these patients presented increased cerebrospinal fluid (CSF) glucose. Our analysis also highlights underestimated comorbidities such as pulmonary disease to act as precipitating conditions in WND, as they were significantly increased amongst deceased patients. CSF glucose and the role of pulmonary diseases need to be revaluated either retrospectively or prospectively in WND patient cohorts, as they may be linked to increased mortality risk.
PubMed: 36136647
DOI: 10.3390/tropicalmed7090236 -
Microorganisms Jul 2023Higher valency pneumococcal conjugate vaccines (PCV15 and PCV20) have been developed to address the disease burden of current non-vaccine serotypes. This review... (Review)
Review
Systematic Literature Review of the Epidemiological Characteristics of Pneumococcal Disease Caused by the Additional Serotypes Covered by the 20-Valent Pneumococcal Conjugate Vaccine.
Higher valency pneumococcal conjugate vaccines (PCV15 and PCV20) have been developed to address the disease burden of current non-vaccine serotypes. This review describes the epidemiological characteristics of serotypes beyond PCV13 (serotypes 8, 10A, 11A, 12F, 15B/C, 22F, and 33F; PCV20nonPCV13 serotypes). Peer-reviewed studies published between 1 January 2010 (the year PCV13 became available) and 18 August 2020 were systematically reviewed (PROSPERO number: CRD42021212875). Data describing serotype-specific outcomes on disease proportions, incidence, severity, and antimicrobial non-susceptibility were summarized for individual and aggregate PCV20nonPCV13 serotypes by age group and by type and duration of pediatric PCV immunization program. Of 1168 studies, 127 (11%) were included in the analysis. PCV20nonPCV13 serotypes accounted for 28% of invasive pneumococcal disease (IPD), although the most frequent serotypes differed between children (10A, 15B/C) and adults (8, 12F, 22F). In children, serotype 15B/C tended to be more frequently associated with pneumococcal meningitis and acute otitis media; in adults, serotype 8 was more frequently associated with pneumonia and serotype 12F with meningitis. Serotypes 10A and 15B/C in children and 11A and 15B/C in adults were often associated with severe IPD. Serotype 15B/C was also among the most frequently identified penicillin/macrolide non-susceptible PCV20nonPCV13 serotypes. These results could inform decision making about higher valency PCV choice and use.
PubMed: 37512988
DOI: 10.3390/microorganisms11071816 -
Neuro-oncology Jun 2023Quantitative imaging analysis through radiomics is a powerful technology to non-invasively assess molecular correlates and guide clinical decision-making. There has been...
BACKGROUND
Quantitative imaging analysis through radiomics is a powerful technology to non-invasively assess molecular correlates and guide clinical decision-making. There has been growing interest in image-based phenotyping for meningiomas given the complexities in management.
METHODS
We systematically reviewed meningioma radiomics analyses published in PubMed, Embase, and Web of Science until December 20, 2021. We compiled performance data and assessed publication quality using the radiomics quality score (RQS).
RESULTS
A total of 170 publications were grouped into 5 categories of radiomics applications to meningiomas: Tumor detection and segmentation (21%), classification across neurologic diseases (54%), grading (14%), feature correlation (3%), and prognostication (8%). A majority focused on technical model development (73%) versus clinical applications (27%), with increasing adoption of deep learning. Studies utilized either private institutional (50%) or public (49%) datasets, with only 68% using a validation dataset. For detection and segmentation, radiomic models had a mean accuracy of 93.1 ± 8.1% and a dice coefficient of 88.8 ± 7.9%. Meningioma classification had a mean accuracy of 95.2 ± 4.0%. Tumor grading had a mean area-under-the-curve (AUC) of 0.85 ± 0.08. Correlation with meningioma biological features had a mean AUC of 0.89 ± 0.07. Prognostication of the clinical course had a mean AUC of 0.83 ± 0.08. While clinical studies had a higher mean RQS compared to technical studies, quality was low overall with a mean RQS of 6.7 ± 5.9 (possible range -8 to 36).
CONCLUSIONS
There has been global growth in meningioma radiomics, driven by data accessibility and novel computational methodology. Translatability toward complex tasks such as prognostication requires studies that improve quality, develop comprehensive patient datasets, and engage in prospective trials.
Topics: Humans; Meningioma; Prospective Studies; Neoplasm Grading; Meningeal Neoplasms
PubMed: 36723606
DOI: 10.1093/neuonc/noad028 -
Scientific Reports Feb 2022The influence of exposure to hormonal treatments, particularly cyproterone acetate (CPA), has been posited to contribute to the growth of meningiomas. Given the... (Meta-Analysis)
Meta-Analysis
The influence of exposure to hormonal treatments, particularly cyproterone acetate (CPA), has been posited to contribute to the growth of meningiomas. Given the widespread use of CPA, this systematic review and meta-analysis attempted to assess real-world evidence of the association between CPA and the occurrence of intracranial meningiomas. Systematic searches of Ovid MEDLINE, Embase and Cochrane Controlled Register of Controlled Trials, were performed from database inception to 18th December 2021. Four retrospective observational studies reporting 8,132,348 patients were included in the meta-analysis. There was a total of 165,988 subjects with usage of CPA. The age of patients at meningioma diagnosis was generally above 45 years in all studies. The dosage of CPA taken by the exposed group (n = 165,988) was specified in three of the four included studies. All studies that analyzed high versus low dose CPA found a significant association between high dose CPA usage and increased risk of meningioma. When high and low dose patients were grouped together, there was no statistically significant increase in risk of meningioma associated with use of CPA (RR = 3.78 [95% CI 0.31-46.39], p = 0.190). Usage of CPA is associated with increased risk of meningioma at high doses but not when low doses are also included. Routine screening and meningioma surveillance by brain MRI offered to patients prescribed with CPA is likely a reasonable clinical consideration if given at high doses for long periods of time. Our findings highlight the need for further research on this topic.
Topics: Androgen Antagonists; Cyproterone Acetate; Female; Humans; Magnetic Resonance Imaging; Male; Meningeal Neoplasms; Meningioma; Middle Aged; Observational Studies as Topic; Risk Assessment; Risk Factors
PubMed: 35121790
DOI: 10.1038/s41598-022-05773-z -
Annals of Clinical and Translational... Jun 2024Fabry disease is caused by enzymatic defects in alpha-galactosidase A that leads to the accumulation of glycosphingolipids throughout the body, resulting in a...
OBJECTIVE
Fabry disease is caused by enzymatic defects in alpha-galactosidase A that leads to the accumulation of glycosphingolipids throughout the body, resulting in a multisystemic disorder. The most common neurological manifestations are neuropathic pain, autonomic nervous system dysfunction and strokes, but some rarer neurological manifestations exist. Among these, aseptic meningitis is a possible complication. Our objectives were to measure the prevalence of this complication in a cohort of patients with Fabry disease, and to describe its clinical features.
METHODS
We conducted a retrospective review of Fabry disease patients followed at our tertiary referral center between 1995 and September 2023 with at least one episode of meningitis, and performed a systematic review to identify similar published cases.
RESULTS
Four patients out of 107 (3.7%) had at least one episode of aseptic meningitis. Our systematic review identified 25 other observations. The median age of these 29 patients was 29.0 years, the median cerebrospinal fluid leukocyte count was 24 cells/mm3 with a predominance of lymphocytes in 64.7% of cases. In 82.8% of the patients, the diagnosis of Fabry disease was unknown before the meningitis. Large artery stenosis was present in 17.2% of patients and 57.1% of patients had a recent stroke concomitant with the meningitis. Several differential diagnoses were evoked, such as multiple sclerosis or central nervous system vasculitis.
INTERPRETATION
Our study suggests that Fabry disease should be considered as a cause of aseptic meningitis. The pathophysiological mechanisms underlying meningeal inflammation remain largely unknown but may reflect the dysregulation of pro-inflammatory signaling pathways.
Topics: Humans; Fabry Disease; Meningitis, Aseptic; Adult; Male; Female; Retrospective Studies; Middle Aged; Young Adult; Adolescent; Aged; Child
PubMed: 38717582
DOI: 10.1002/acn3.52043 -
Cancers Jan 2023The safety and efficacy of various pharmacotherapeutic regimens on refractory meningiomas have been the focus of investigations. We present a comprehensive review of the... (Review)
Review
The safety and efficacy of various pharmacotherapeutic regimens on refractory meningiomas have been the focus of investigations. We present a comprehensive review of the previous efforts and the current state of ongoing clinical trials. A PRISMA-compliant review of the MEDLINE and ClinicalTrial.gov databases of the National Library of Medicine were performed. The primary outcomes of interest for included articles were radiographic response, overall survival, progression-free survival, six-month progression-free survival, and adverse events. Overall, 34 completed trials and 27 ongoing clinical trials were eligible. Six-month progression-free survival was reported in 6-100% of patients in the completed studies. Hematological disorders were the most common adverse events. Of the ongoing clinical trials identified, nine studies are phase I clinical trials, eleven are phase II trials, two are phase I and II trials, one is phase II and III, and two trials do not have a designated phase. Currently, there is no effective chemotherapy for refractory or recurrent meningiomas. Several promising targeted agents have been developed and are currently being investigated in the hope of identifying novel therapeutic strategies for the treatment of this pathology.
PubMed: 36672431
DOI: 10.3390/cancers15020483 -
Brain & Spine 2023Hemispherectomy/hemispherotomy has been employed in the management of catastrophic epilepsy. However, initial reports on the associated mortality and morbidity raised... (Review)
Review
INTRODUCTION
Hemispherectomy/hemispherotomy has been employed in the management of catastrophic epilepsy. However, initial reports on the associated mortality and morbidity raised several concerns regarding the technique's safety. Their actual, current incidence needs to be systematically examined to redefine hemispherotomy's exact role.
RESEARCH QUESTION
Our current study examined their incidence and evaluated the association of the various hemispherotomy surgical techniques with the reported complications.
MATERIAL & METHODS
A PRISMA-compliant systematic review and meta-analysis was performed. We searched PubMed, Scopus, and Web of Science until December 2022. Fixed- and random-effects models were employed. Egger's regression test was used for estimating the publication bias, while subgroup analysis was utilized for defining the role of the different hemispherotomy techniques.
RESULTS
We retrieved a total of 37 studies. The overall procedure mortality was 5%, with a reported mortality of 7% for hemispherectomy and 3% for hemispherotomy. The reported mortality has decreased over the last 30 years from 32% to 2%. Among the observed post-operative complications aseptic meningitis and/or fever occurred in 33%. Hydrocephalus requiring a shunt insertion occurred in 16%. Hematoma evacuation was necessary in 8%, while subgaleal effusion in another 8%. Infections occurred in 11%. A novel post-operative cranial nerve deficit occurred in 11%, while blood transfusion was necessary in 28% of the cases.
DISCUSSION AND CONCLUSION
Our current analysis demonstrated that the evolution from hemispherectomy to hemispherotomy along with neuroanesthesia advances, had a tremendous impact on the associated mortality and morbidity. Hemispherotomy constitutes a safe surgical procedure in the management of catastrophic epilepsies.
PubMed: 38021002
DOI: 10.1016/j.bas.2023.101766 -
Clinical Microbiology and Infection :... Dec 2022Rapid and accurate diagnosis of herpes simplex virus (HSV)-1 and -2 (HSV1/2) in cerebrospinal fluid (CSF) is important for patient management. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Rapid and accurate diagnosis of herpes simplex virus (HSV)-1 and -2 (HSV1/2) in cerebrospinal fluid (CSF) is important for patient management.
OBJECTIVES
Summarize the diagnostic accuracy of commercial rapid sample-to-answer PCR assays (results in <90 minutes, without a separate nucleic acid extraction step) for HSV1/2 detection in CSF.
DATA SOURCES
Four databases (MEDLINE, EMBASE, Scopus, and CENTRAL) and five conference abstract datasets from January 2012 to March 2022.
STUDY ELIGIBILITY CRITERIA
Eligible diagnostic accuracy studies provided sufficient data for the construction of a standard diagnostic accuracy two-by-two table.
PARTICIPANTS
Patients with suspected meningitis and/or encephalitis.
TESTS
FilmArray Meningitis-Encephalitis Panel and Simplexa HSV 1&2 Direct Kit PCR.
REFERENCE STANDARD
Real-time PCR assay.
ASSESSMENT OF RISK OF BIAS
Two investigators independently extracted data, rated risk of bias, and assessed quality using QUADAS-2. METHODS OF DATA SYNTHESIS: Accuracy estimates were pooled using Bayesian random effects models.
RESULTS
Thirty-one studies were included (27 FilmArray; 4 Simplexa), comprising 9924 samples, with 95 HSV-1 and 247 HSV-2 infections. Pooled FilmArray sensitivities were 84.3% (95% credible interval, 72.3-93.0) and 92.9% (95% credible interval (CrI), 82.0-98.5) for HSV-1 and HSV-2, respectively; specificities were 99.8% (95% CrI, 99.6-99.9) and 99.9% (95% CrI, 99.9-100). Pooled Simplexa sensitivities were 97.1% (95% CrI, 88.1-99.6) and 97.9% (95% CrI, 89.6-99.9), respectively; specificities were 98.9% (95% CrI, 96.8-99.7) and 98.9% (95% CrI, 97.1-99.7). Pooled FilmArray sensitivities favoured industry-sponsored studies by 10.0 and 13.0 percentage points for HSV-1 and HSV-2, respectively. Incomplete reporting frequently led to unclear risk of bias. Several FilmArray studies did not fully report true negative data leading to their exclusion.
CONCLUSIONS
Our results suggest Simplexa is accurate for HSV1/2 detection in CSF. Moderate FilmArray sensitivity for HSV-1 suggests additional testing and/or repeat CSF sampling is required for suspected HSV encephalitis when the HSV-1 result is negative. Low prevalence of HSV-1 infections limited summary estimates' precision. Underreporting of covariates limited exploration of heterogeneity.
Topics: Humans; Herpesvirus 1, Human; Bayes Theorem; Sensitivity and Specificity; Encephalitis, Herpes Simplex; Real-Time Polymerase Chain Reaction; Meningitis; Cerebrospinal Fluid
PubMed: 35718347
DOI: 10.1016/j.cmi.2022.06.004 -
Journal of Craniovertebral Junction &... 2022Spondyloptosis is a rare presentation of cervical spine traumatism where listhesis is more than 100%. Traumatic cervical spine spondyloptosis (TCS) is one of the least... (Review)
Review
BACKGROUND
Spondyloptosis is a rare presentation of cervical spine traumatism where listhesis is more than 100%. Traumatic cervical spine spondyloptosis (TCS) is one of the least discussed forms of cervical spine traumatisms because of its rarity and the gravity of patient's condition, limiting good management, and the number of reported cases.
OBJECTIVES
This study aimed to discuss clinical, radiological, and best management tools of the aforementioned pathology.
MATERIALS AND METHODS
Scopus, ScienceDirect, PubMed, and Google Scholar databases were searched for English articles about traumatic cervical spondyloptosis. Titles, abstracts, or author-specified keywords that contain the words "spondyloptosis" AND "cervical" AND "spine" were identified. There were no time limits. In sum, 542 records were identified, 63 records were screened, and 46 records were included in this review, describing 64 clinical cases of traumatic cervical spondyloptosis. The clinical cases of two patients managed at our department are also presented and included. In the end, 66 cases were included in this study. Demographics, clinics, radiology, management tools, and outcome of the reviewed cases were discussed. This study was conducted in agreement with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement 2009. The American Spinal Injury Association Impairment Scale (AIS) score was used to evaluate the clinical presentations.
RESULTS
This review included 66 patients consisting of 46 males (70%) and 20 females (30%), with a mean age of 41 years. The accident was indicated in 62 cases; it was a road traffic accident in 29 cases (46%), a fall in 24 cases (38%), and motor vehicle accident in 15 cases (24%). The lesion was iatrogenic in four patients. Twenty-one patients were received without motor or sensitive deficit and so scored Grade E on AIS, 10 with Grade D, 11 Grade C, four Grade B, and 20 with Grade A. On imaging, spondyloptosis involved the C1-C2 segment in two cases (3%), C2-C3 in three cases (5.5%), C3-C4 in one case (1.5%), C4-C5 in six cases (9%), C5-C6 in nine cases (13%), C6-C7 in 20 cases (30%), and C7-T1 in 26 cases (38%). In all cases, there was either fracture or dislocation in posterior elements. Bilateral pedicles or facet joint fractures were noted in 53% of the 56 patients where the associated lesions were described, but it jumps to 89% when a vertebra is projected in front of another. In two cases, there was no mention of closed reduction via transcranial traction; in 13 cases (20%), it was avoided for a reason (child, patient's refusal,…). In the 51 cases where the traction was clearly applied, 17 cases (33%) were reduced totally; in 13 cases (25%) the reduction was partial; it failed in 19 cases (37%); and in the remaining cases, the result was not clear. Traction weight varied from 4 kg to 27.2 kg, applied from 6 h to 20 days. Where total reduction was achieved, an average weight of 11.9 kg with proximal average time of 6 days was needed, whereas an average of 11.5 kg was needed for partial reduction with proximal average time of 10 days. 62 patients were operated rather in one or two times. Anterior approach was used in 20 patients (32%), a posterior approach in 14 patients (23%), and combined anterior/posterior approaches in 28 patients (45%). In four patients, the outcome was not available; in the remaining 62 cases, an improvement of an initial deficit was noted in 25 patients (40%), conservation of an initial motor force integrity was noted in 19 patients (30%), and nine patients (14.5%) kept the same initial deficit. Few complications were declared: dura tears with cerebrospinal fluid leaks, meningitis, esophageal laceration, and vocal cord paralysis. There was a mortality of 11% (seven cases).
CONCLUSION
Traumatic cervical spine spondyloptosis predominates in the lowest levels of the cervical spine, allowed in all cases by a failure in posterior elements. It is a lesion with the worst clinical presentation. Traumatic cervical spine spondyloptosis is highly instable, imposing urgent reduction followed by surgical stabilization. At the limit of the reviewed cases, outcome is in general good, but mortality is still important.
PubMed: 35386237
DOI: 10.4103/jcvjs.jcvjs_132_21