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Clinical and Translational Radiation... Jul 2022Radiotherapy (RT) is a cornerstone treatment strategy for brain tumours. Besides cytotoxicity, RT can cause disruption of the blood-brain barrier (BBB), resulting in an... (Review)
Review
Radiotherapy (RT) is a cornerstone treatment strategy for brain tumours. Besides cytotoxicity, RT can cause disruption of the blood-brain barrier (BBB), resulting in an increased permeability into the surrounding brain parenchyma. Although this effect is generally acknowledged, it remains unclear how and to what extent different radiation schemes affect BBB integrity. The aim of this systematic review and meta-analysis is to investigate the effect of photon RT regimens on BBB permeability, including its reversibility, in clinical and preclinical studies. We systematically reviewed relevant clinical and preclinical literature in PubMed, Embase, and Cochrane search engines. A total of 69 included studies (20 clinical, 49 preclinical) were qualitatively and quantitatively analysed by meta-analysis and evaluated on key determinants of RT-induced BBB permeability in different disease types and RT protocols. Qualitative data synthesis showed that 35% of the included clinical studies reported BBB disruption following RT, whereas 30% were inconclusive. Interestingly, no compelling differences were observed between studies with different calculated biological effective doses based on the fractionation schemes and cumulative doses; however, increased BBB disruption was noted during patient follow-up after treatment. Qualitative analysis of preclinical studies showed RT BBB disruption in 78% of the included studies, which was significantly confirmed by meta-analysis (p < 0.01). Of note, a high risk of bias, publication bias and a high heterogeneity across the studies was observed. This systematic review and meta-analysis sheds light on the impact of RT protocols on BBB integrity and opens the discussion for integrating this factor in the decision-making process of future RT, with better study of its occurrence and influence on concomitant or adjuvant therapies.
PubMed: 35601799
DOI: 10.1016/j.ctro.2022.04.013 -
Neuro-oncology Practice Feb 2021The aim of our study is to determine the incidence, timing, and risk factors for cerebral vasculopathy after cranial proton and photon radiation for pediatric brain... (Review)
Review
BACKGROUND
The aim of our study is to determine the incidence, timing, and risk factors for cerebral vasculopathy after cranial proton and photon radiation for pediatric brain tumors.
METHODS
We performed a single-institution retrospective review of a cohort of children treated with proton radiation for brain tumors. MRA and/or MRI were reviewed for evidence of cerebral vascular stenosis and infarcts. Twenty-one similar studies (17 photon, 4 proton) were identified by systematic literature review.
RESULTS
For 81 patients with median follow-up of 3 years, the rates of overall and severe vasculopathy were 9.9% and 6.2% respectively, occurring a median of 2 years post radiation. Dose to optic chiasm greater than 45 Gy and suprasellar location were significant risk factors. Results were consistent with 4 prior proton studies (752 patients) that reported incidence of 5% to 6.7%, 1.5 to 3 years post radiation. With significantly longer follow-up (3.7-19 years), 9 studies (1108 patients) with traditional photon radiation reported a higher rate (6.3%-20%) and longer time to vasculopathy (2-28 years). Significant risk factors were neurofibromatosis type 1 (NF-1; rate 7.6%-60%) and suprasellar tumors (9%-20%). In 10 studies with photon radiation (1708 patients), the stroke rate was 2% to 18.8% (2.3-24 years post radiation).
CONCLUSIONS
Childhood brain tumor survivors need screening for vasculopathy after cranial radiation, especially with higher dose to optic chiasm, NF-1, and suprasellar tumors. Prospective studies are needed to identify risk groups, and ideal modality and timing, for screening of this toxicity.
PubMed: 33664967
DOI: 10.1093/nop/npaa061 -
Journal of Clinical Movement Disorders 2017Chorea is a hyperkinetic movement disorder consisting of involuntary irregular, flowing movements of the trunk, neck or face. Although Huntington's disease is the most... (Review)
Review
Chorea is a hyperkinetic movement disorder consisting of involuntary irregular, flowing movements of the trunk, neck or face. Although Huntington's disease is the most common cause of chorea in adults, chorea can also result from many other neurodegenerative, metabolic, and autoimmune conditions. While the pathophysiology of these different conditions is quite variable, recent advances in functional imaging have enabled the development of new methods for analysis of brain activity and neuronal dysfunction. In this paper we review the growing body of functional imaging data that has been performed in chorea syndromes and identify particular trends, which can be used to better understand the underlying network changes within the basal ganglia. While it can be challenging to identify whether changes are primary, secondary, or compensatory, identification of these trends can ultimately be useful in diagnostic testing and treatment in many of the conditions that cause chorea.
PubMed: 28649394
DOI: 10.1186/s40734-017-0056-0 -
Movement Disorders : Official Journal... Jul 2022Mutations in the GBA gene cause Gaucher's disease (GD) and constitute the most frequent genetic risk factor for idiopathic Parkinson's disease (iPD). Nonmanifesting... (Review)
Review
BACKGROUND
Mutations in the GBA gene cause Gaucher's disease (GD) and constitute the most frequent genetic risk factor for idiopathic Parkinson's disease (iPD). Nonmanifesting carriers of GBA mutations/variants (GBA-NMC) constitute a potential PD preclinical population, whereas PD patients carrying some GBA mutations/variants (GBA-PD) have a higher risk of a more aggressive disease course. Different neuroimaging techniques are emerging as potential biomarkers in PD and have been used to study GBA-associated parkinsonism.
OBJECTIVE
The aim is to critically review studies applying neuroimaging to GBA-associated parkinsonism.
METHODS
Literature search was performed using PubMed and EMBASE databases (last search February 7, 2022). Studies reporting neuroimaging findings in GBA-PD, GD with and without parkinsonism, and GBA-NMC were included.
RESULTS
Thirty-five studies were included. In longitudinal studies, GBA-PD patients show a more aggressive disease than iPD at both structural magnetic resonance imaging and 123-fluoropropylcarbomethoxyiodophenylnortropane single-photon emission computed tomography. Fluorodeoxyglucose-positron emission tomography and brain perfusion studies reported a greater cortical involvement in GBA-PD compared to iPD. Overall, contrasting evidence is available regarding GBA-NMC for imaging and clinical findings, although subtle differences have been reported compared with healthy controls with no mutations.
CONCLUSIONS
Although results must be interpreted with caution due to limitations of the studies, in line with previous clinical observations, GBA-PD showed a more aggressive disease progression in neuroimaging longitudinal studies compared to iPD. Cognitive impairment, a "clinical signature" of GBA-PD, seems to find its neuroimaging correlate in the greater cortical burden displayed by these patients as compared to iPD. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Gaucher Disease; Glucosylceramidase; Humans; Neuroimaging; Parkinson Disease; Parkinsonian Disorders
PubMed: 35521899
DOI: 10.1002/mds.29047 -
Advances in Radiation Oncology 2023The aim of this study was to comprehensively review all studies examining clinical outcomes of craniospinal irradiation with proton radiotherapy for medulloblastoma (MB)... (Review)
Review
PURPOSE
The aim of this study was to comprehensively review all studies examining clinical outcomes of craniospinal irradiation with proton radiotherapy for medulloblastoma (MB) to determine whether theoretical dosimetric advantages have translated into superior clinical outcomes (including survival and toxicities) compared with traditional photon-based techniques.
METHODS AND MATERIALS
We performed a systematic review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles reporting on clinical outcomes of pediatric and/or adult patients with MB treated with proton radiotherapy were included. Evidence quality was assessed using a modified Newcastle Ottawa scale and GRADE score.
RESULTS
Thirty-five studies were included, with a total of 2059 patients reported (representing an estimated 630-654 unique patients). None of the studies were randomized, 12 were comparative, 9 were prospective, 3 were mixed, and 22 were retrospective. Average mean/median follow-up was 5.0 years (range, 4 weeks to 12.6 years). The majority of studies (n = 19) reported on treatment with passive scatter proton beams exclusively. Average study quality was 6.0 out of 9 (median, 6; standard deviation, 1.6). Nine studies scored ≥8 out of 9 on the modified Newcastle Ottawa Scale; an overall "moderate" GRADE score was assigned. Well-designed comparative cohort studies with adequate follow-up demonstrate superior neurocognitive outcomes, lower incidence of hypothyroidism (23% vs 69%), sex hormone deficiency (3% vs 19%), greater heights, and reduced acute toxicities in patients treated with protons compared to photons. Overall survival (up to 10 years), progression-free survival (up to 10 years), brain stem injury, and other endocrine outcomes were similar to those reported for photon radiation. There was insufficient evidence to make conclusions on endpoints of quality of life, ototoxicity, secondary malignancy, alopecia, scoliosis, cavernomas, and cerebral vasculopathy.
CONCLUSIONS
Moderate-grade evidence supports proton radiotherapy as a preferred treatment for craniospinal irradiation of MB based on equivalent disease control and comparable-to-improved toxicity versus photon beam radiation therapy.
PubMed: 37008255
DOI: 10.1016/j.adro.2023.101189 -
Current Urology Mar 2022Misdiagnosis of benign renal neoplasms can lead to unnecessary surgical resections, which increases the risk of other morbidities and mortality. Therefore, it is crucial... (Review)
Review
Misdiagnosis of benign renal neoplasms can lead to unnecessary surgical resections, which increases the risk of other morbidities and mortality. Therefore, it is crucial to find a diagnostic modality for differentiation between benign and malignant renal masses. In the current study, we summarized published pieces of evidence concerning the use of technetium-99m (Tc)-sestamibi single-photon emission computed tomography/computed tomography (SPECT/CT) as a promising diagnostic nuclear imaging modality for the differentiation of renal neoplasms. The study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement for Systematic Reviews and Meta-Analyses. We conducted a systematic electronic database search for suitable studies from inception till February 20, 2020 in 9 databases. The risk of bias was assessed for the included studies using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. We identified 9373 records after exclusion of 8978 duplicates using EndNote software. Title and abstract screening resulted in 761 records for further full-text screening. Finally, four studies were included with total sample size of 80 patients. The overall risk of bias was low to moderate. The results of all the included studies supported using Tc-sestamibi SPECT/CT for the differentiation between benign and malignant renal neoplasms. The use of Tc-sestamibi SPECT/CT could be a rapid, less invasive, promising diagnostic modality for histological diagnosis and staging of renal neoplasm, as well as monitoring post-therapy tumor's response. However, more studies with large sample sizes are essential to confirm the reliability and accuracy of this modality for usage.
PubMed: 35633856
DOI: 10.1097/CU9.0000000000000089 -
Osteoporosis International : a Journal... Aug 2021Older adults spend more than 8 h/day in sedentary behaviours. Detrimental effects of sedentary behaviour (SB) on health are established, yet little is known about SB and... (Review)
Review
Older adults spend more than 8 h/day in sedentary behaviours. Detrimental effects of sedentary behaviour (SB) on health are established, yet little is known about SB and bone health (bone mineral density; BMD) in older adults. The purpose of this review is to examine associations of SB with BMD in older adults. Five electronic databases were searched: Web of Science (Core Collection); PubMed; EMBASE; Sports Medicine and Education and PsycInfo. Inclusion criteria were healthy older adults mean age ≥ 65 years; measured SB and measured BMD using dual-energy X-ray absorptiometry. Quality was assessed using National Institute of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. After excluding duplicates 17813 papers were assessed; 17757 were excluded on title/abstract, 49 at full text, resulting in two prospective and five cross-sectional observational studies reviewed. Four were rated 'good' and three were rated 'fair' using the quality assessment criteria. Findings varied across the studies and differed by gender. In women, four studies reported significant positive associations of SB with BMD at different sites, and two found significant negative associations. Five studies which examined both men and women, men reported negative or no associations of SB with femoral neck, pelvic, whole body, spine or leg BMD. Whilst these findings suggest differences between men and women in the associations of SB with BMD, they may be due to the varying anatomical sections examined for BMD, the different methods used to measure SB, the varied quality of the studies included and the limited number of published findings.
Topics: Absorptiometry, Photon; Aged; Bone Density; Cross-Sectional Studies; Female; Femur Neck; Humans; Male; Prospective Studies; Sedentary Behavior
PubMed: 33768342
DOI: 10.1007/s00198-021-05918-2 -
European Stroke Journal Dec 2023The pathogenesis of cerebral small vessel disease (cSVD) remains elusive despite evidence of an association between white matter hyperintensities (WMH) and endothelial... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The pathogenesis of cerebral small vessel disease (cSVD) remains elusive despite evidence of an association between white matter hyperintensities (WMH) and endothelial cerebrovascular dysfunction. Neurovascular coupling (NVC) may be a practical alternative measure of endothelial function. We performed a systematic review of reported associations between NVC and cSVD.
METHODS
EMBASE and PubMed were searched for studies reporting an association between any STRIVE-defined marker of cSVD and a measure of NVC during functional magnetic resonance imaging, transcranial Doppler, positron emission tomography, near-infrared spectroscopy or single-photon emission computed tomography, from inception to November 3rd, 2022. Where quantitative data was available from studies using consistent tests and analyses, results were combined by inverse-variance weighted random effects meta-analysis.
FINDINGS
Of 29 studies (19 case-controls; 10 cohorts), 26 reported decreased NVC with increasing severity of cSVD, of which 18 were individually significant. In 28 studies reporting associations with increasing WMH, 25 reported reduced NVC. Other markers of cSVD were associated with reduced NVC in: eight of nine studies with cerebral microbleeds (six showing a significant effect); three of five studies with lacunar stroke; no studies reported an association with enlarged perivascular spaces. Specific SVD diseases were particularly associated with reduced NVC, including six out of seven studies in cerebral amyloid angiopathy and all four studies in CADASIL. In limited meta-analyses, %BOLD occipital change to a visual stimulus was consistently reduced with more severe WMH (seven studies, SMD -1.51, < 0.01) and increasing microbleeds (seven studies, SMD -1.31, < 0.01).
DISCUSSION AND CONCLUSION
In multiple, small studies, neurovascular coupling was reduced in patients with increasing severity of all markers of cSVD in sporadic disease, CAA and CADASIL. Cerebrovascular endothelial dysfunction, manifest as impaired NVC, may be a common marker of physiological dysfunction due to small vessel injury that can be easily measured in large studies and clinical practice.
Topics: Humans; CADASIL; Neurovascular Coupling; Tomography, X-Ray Computed; Cerebral Small Vessel Diseases; Cerebral Hemorrhage
PubMed: 37697725
DOI: 10.1177/23969873231196981 -
Journal of Oncology 2019Radiotherapy (RT) plays a fundamental role in the treatment of pediatric central nervous system (CNS) malignancies, but its late sequelae are still a challenging... (Review)
Review
BACKGROUND
Radiotherapy (RT) plays a fundamental role in the treatment of pediatric central nervous system (CNS) malignancies, but its late sequelae are still a challenging question. Despite developments in modern high-conformal photon techniques and proton beam therapy (PBT) are improving the normal tissues dose-sparing while maintaining satisfactory target coverage, clinical advantages supporting the optimal treatment strategy have to be better evaluated in long-term clinical studies and assessed in further radiobiological analyses. Our analysis aimed to systematically review current knowledge on the dosimetric advantages of PBT in the considered setting, which should be the basis for future specific studies.
MATERIALS AND METHODS
A PubMed and Google Scholar search was conducted in June 2019 to select dosimetric studies comparing photon versus proton RT for pediatric patients affected by CNS tumors. Then, a systematic review and meta-analysis according to the PRISMA statement was performed. Average and standard deviation values of Conformity Index, Homogeneity Index, and mean and maximum doses to intracranial and extracranial organs at risk (OARs) were specifically evaluated for secondary dosimetric comparisons. The standardized mean differences (SMDs) for target parameters and the mean differences (MDs) for OARs were summarized in forest plots ( < 0.05 was considered statistically significant). Publication bias was also assessed by the funnel plot and Egger's regression test.
RESULTS
Among the 88 identified papers, a total of twelve studies were included in the meta-analysis. PBT showed dosimetric advantages in target homogeneity (significant especially in the subgroup comparing PBT and 3D conformal RT), as well as in the dose sparing of almost all analyzed OARs (significantly superior results for brainstem, normal brain, and hippocampal dose constraints and for extracranial OARs parameters, excluding the kidneys). Publication bias was observed for Conformity Index.
CONCLUSION
Our analysis supports the evidence of dosimetric advantages of PBT over photon RT, especially in the dose sparing of normal growing tissues. Confirmations from wider well-designed studies are required.
PubMed: 31885580
DOI: 10.1155/2019/5879723 -
Journal of Clinical Medicine May 2023Takayasu's arteritis (TA) is a type of vasculitis in which inflammation develops in large vessels, especially in the aorta and its branches. Our study aims to determine... (Review)
Review
Takayasu's arteritis (TA) is a type of vasculitis in which inflammation develops in large vessels, especially in the aorta and its branches. Our study aims to determine the prevalence and type of ocular manifestations in TA. A systematic literature search was conducted in December 2022 using three electronic databases (PubMed, Scopus, and Web of Science). The following data were extracted from each article: the name of the first author; the patient's age, sex, and origin (continent); circumstances connected with the diagnosis of TA; symptoms given by the patients; reported ocular manifestations; and administered treatment. The final analysis was based on data collected from 122 cases. Retinal ischemia, followed by optic neuropathy, cataract, and retinal artery occlusion, were the most prevalent eye conditions associated with the disease. Systemic steroid therapy, vascular procedures, and methotrexate were mainly used to treat pulseless disease. Patients mostly complained of gradual vision acuity loss, sudden vision acuity loss, ocular pain, and amaurosis fugax. The diagnosis of Takayasu's arteritis should be considered in patients presenting symptoms of visual decline/loss, ocular pain, or signs of retinal ischemia, optic neuropathy, or early cataract formation. A proper diagnosis is crucial to ensure the patient receives treatment without significant delay.
PubMed: 37297942
DOI: 10.3390/jcm12113745