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Biology Feb 2022Pemphigus vulgaris (PV) is an IgG-mediated autoimmune disease characterised by epithelial cell-cell detachment (acantholysis) resulting in mucocutaneous blistering. The... (Review)
Review
BACKGROUND
Pemphigus vulgaris (PV) is an IgG-mediated autoimmune disease characterised by epithelial cell-cell detachment (acantholysis) resulting in mucocutaneous blistering. The exact pathogenesis of blister formation is unknown and this has hampered the development of non-steroidal, mechanism-based treatments for this autoimmune disease. This systematic review aims to investigate the role of caspases in the pathogenesis of PV to inform the choice of more targeted therapeutic agents.
METHODS
A systematic search of MEDLINE/PubMed and Scopus databases was conducted to identify eligible studies. Multiple phases of inclusion and exclusion of the primary articles were conducted in pairs, and studies were recorded and analysed according to the latest version of the preferred reporting items for systematic reviews and meta-analyses (PRISMA). Risk of bias assessment was conducted for extracted in vivo animal intervention studies using SYRCLE's risk of bias tool.
RESULTS
Eight articles from a total of 2338 in vitro, in vivo, and human studies met the inclusion criteria, with a high degree of inter-rater reliability. By and large, the results show that caspase activation was pathogenic in experimental PV because pan-caspase inhibitors could block or reduce PV acantholysis and blistering in vitro and in vivo, respectively. The pathogenic pathways identified involved caspase-1 and caspase-3. One study failed to show any improvement in the PV model with a caspase inhibitor. The majority of animal studies had high or unclear risk of bias.
CONCLUSION
There are consistent data pointing towards a pathogenic role of caspase activation in PV acantholysis. However, high-quality evidence to confirm that caspase inhibition can prevent PV-induced blistering in vivo is limited. Therefore, further research is required to test the preclinical efficacy of caspase inhibitors in PV.
PubMed: 35205180
DOI: 10.3390/biology11020314 -
The Cochrane Database of Systematic... Sep 2022Congenital cataracts are lens opacities in one or both eyes of babies or children present at birth. These may cause a reduction in vision severe enough to require... (Review)
Review
BACKGROUND
Congenital cataracts are lens opacities in one or both eyes of babies or children present at birth. These may cause a reduction in vision severe enough to require surgery. Cataracts are proportionally the most treatable cause of visual loss in childhood, and are a particular problem in low-income countries, where early intervention may not be possible. Paediatric cataracts provide different challenges to those in adults. Intense inflammation, amblyopia (vision is obstructed by cataract from birth which prevents normal development of the visual system), posterior capsule opacification and uncertainty about the final trajectory of ocular growth parameters can affect results of treatment. Two options currently considered for children under 2 years of age with bilateral congenital cataracts are: (i) intraocular lens (IOL) implantation; or (ii) leaving a child with primary aphakia (no lens in the eye), necessitating the need for contact lenses or aphakic glasses. Other important considerations regarding surgery include the prevention of visual axis opacification (VAO), glaucoma and the route used to perform lensectomy.
OBJECTIVES
To assess the effectiveness of infant cataract surgery or lensectomy to no surgery for bilateral congenital cataracts in children aged 2 years and under.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; which contains the Cochrane Eyes and Vision Trials Register; 2022, Issue 1); Ovid MEDLINE; Ovid Embase; the ISRCTN registry; ClinicalTrials.gov and the WHO ICTRP. The date of the search was 25 January 2022.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) that compared infant cataract surgery or lensectomy to no surgery, in children with bilateral congenital cataracts aged 2 years and younger. This update (of a review published in 2001 and updated in 2006) does not include children over 2 years of age because they have a wider variety of aetiologies, and are therefore managed differently, and have contrasting outcomes.
DATA COLLECTION AND ANALYSIS
We used standard methods expected by Cochrane. Two review authors extracted data independently. We assessed the risk of bias of included studies using RoB 1 and assessed the certainty of the evidence using GRADE.
MAIN RESULTS
We identified three RCTs that met our inclusion criteria with each trial comparing a different aspect of surgical intervention for this condition. The trials included a total of 79 participants under 2 years of age, were conducted in India and follow-up ranged from 1 to 5 years. Study participants and outcome assessors were not masked in these trials. One study (60 children) compared primary IOL implantation with primary aphakia. The results from this study suggest that there may be little or no difference in visual acuity at 5 years comparing children with pseudophakia (mean logMAR 0.50) and aphakia (mean logMAR 0.59) (mean difference (MD) -0.09 logMAR, 95% confidence intervals (CIs) -0.24 to 0.06; 54 participants; very low-certainty evidence), but the evidence is very uncertain. The evidence is very uncertain as to the effect of IOL implantation compared with aphakia on visual axis opacification (VAO) (risk ratio (RR) 1.29, 95% CI 0.23 to 7.13; 54 participants; very low-certainty evidence). The trial investigators did not report on the cases of amblyopia. There was little evidence of a difference betwen the two groups in cases of glaucoma at 5 years follow-up (RR 0.86, 95% CI 0.24 to 3.10; 54 participants; very low-certainty evidence). Cases of retinal detachment and reoperation rates were not reported. The impact of IOL implantation on adverse effects is very uncertain because of the sparse data available: of the children who were pseudophakic, 1/29 needed a trabeculectomy and 8/29 developed posterior synechiae. In comparison, no trabeculectomies were needed in the aphakic group and 2/25 children had posterior synechiae (54 participants; very low-certainty evidence). The second study (14 eyes of 7 children under 2 years of age) compared posterior optic capture of IOL without vitrectomy versus endocapsular implantations with anterior vitrectomy (commonly called 'in-the-bag surgery'). The authors did not report on visual acuity, amblyopia, glaucoma and reoperation rate. They had no cases of VAO in either group. The evidence is very uncertain as to the effect of in-the-bag implantation in children aged under 1 year. There was a higher incidence of inflammatory sequelae: 4/7 in-the-bag implantation eyes and 1/7 in optic capture eyes (P = 0.04, 7 participants; very low-certainty evidence). We graded the certainty of evidence as low or very low for imprecision in all outcomes because their statistical analysis reported that a sample size of 13 was needed in each group to achieve a power of 80%, whereas their subset of children under the age of 1 year had only 7 eyes in each group. The third study (24 eyes of 12 children) compared a transcorneal versus pars plana route using a 25-gauge transconjunctival sutureless vitrectomy system. The evidence is very uncertain as to the effect of the route chosen on the incidence of VAO, with no cases reported at 1 year follow-up in either group. The investigators did not report on visual acuity, amblyopia, glaucoma, retinal detachment and reoperation rate. The pars plana route had the adverse effects of posterior capsule rupture in 2/12 eyes, and 1/12 eyes needing sutures. Conversely, 1/12 eyes operated on by the transcorneal route needed sutures. We graded the outcomes with very low-certainty because of the small sample size and the absence of a priori sample size calculation.
AUTHORS' CONCLUSIONS
There is no high level evidence for the effectiveness of one type of surgery for bilateral congenital cataracts over another, or whether surgery itself is better than primary aphakia. Further RCTs are required to inform modern practice about concerns, including the timing of surgery, age at which surgery should be undertaken, age for implantation of an IOL and development of complications, such as reoperations, glaucoma and retinal detachment. Standardising the methods used to measure visual function, along with objective monitoring of compliance with the use of aphakic glasses/contact lenses would greatly improve the quality of study data and enable more reliable interpretation of outcomes.
Topics: Amblyopia; Aphakia; Capsule Opacification; Child; Child, Preschool; Glaucoma; Humans; Infant; Infant, Newborn; Lens Implantation, Intraocular; Retinal Detachment
PubMed: 36107778
DOI: 10.1002/14651858.CD003171.pub3 -
The Cochrane Database of Systematic... Jun 2022Endophthalmitis refers to severe infection within the eye that involves the aqueous humor or vitreous humor, or both, and that threatens vision. Most cases of... (Review)
Review
BACKGROUND
Endophthalmitis refers to severe infection within the eye that involves the aqueous humor or vitreous humor, or both, and that threatens vision. Most cases of endophthalmitis are exogenous (i.e. due to inoculation of organisms from an outside source), and most exogenous endophthalmitis is acute and occurs after an intraocular procedure. The mainstay of treatment is emergent administration of broad-spectrum intravitreous antibiotics. Due to their anti-inflammatory effects, steroids in conjunction with antibiotics have been proposed as being beneficial in endophthalmitis management.
OBJECTIVES
To assess the effects of antibiotics combined with steroids versus antibiotics alone for the treatment of acute endophthalmitis following intraocular surgery or intravitreous injection.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2021, Issue 8), MEDLINE Ovid (1946 to August 2021), Embase Ovid (1980 to August 2021), LILACS (Latin American and Caribbean Health Sciences Literature database) (1982 to August 2021), the ISRCTN registry; searched August 2021, ClinicalTrials.gov; searched August 2021, and the WHO International Clinical Trials Registry Platform; searched August 2021. We did not use any date or language restrictions in the electronic searches for trials.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) comparing the effectiveness of adjunctive steroids with antibiotics alone in the management of acute, clinically diagnosed endophthalmitis following intraocular surgery or intravitreous injection. We excluded trials with participants with endogenous endophthalmitis unless outcomes were reported by source of infection. We imposed no restrictions on the method or order of administration, dose, frequency, or duration of antibiotics and steroids.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology, and graded the certainty of the body of evidence for six outcomes using the GRADE classification.
MAIN RESULTS
We included four RCTs with a total of 264 eyes of 264 participants in this review update. The studies were conducted in South Africa, India, and the Netherlands. All studies used intravitreous dexamethasone for adjunctive steroid therapy and a combination of two intravitreous antibiotics that provided gram-positive and gram-negative coverage for the antibiotic therapy. We judged two trials to be at overall low risk of bias, and the other two studies to be at overall unclear risk of bias due to lack of reporting of study methods. Only one study was registered in a clinical trial register. While none of the included studies reported the primary outcome of complete resolution of endophthalmitis as defined in our protocol, one study reported combined anatomical and functional success (i.e. proportion of participants with intraocular pressure of at least 5 mmHg and visual acuity of at least 6/120). Very low certainty evidence suggested no difference in combined success when comparing adjunctive steroid to antibiotics alone (risk ratio (RR) 1.08, 95% confidence interval (CI) 0.80 to 1.45; 32 participants). Low certainty evidence from two studies suggested that adjunctive dexamethasone may result in having a good visual outcome (Snellen visual acuity 6/6 to 6/18) at 3 months compared with antibiotics alone (RR 1.95, 95% CI 1.05 to 3.60; 60 participants); however, the evidence was less conclusive at 12 months (RR 1.12, 95% CI 0.92 to 1.37; 2 studies; 195 participants; low certainty evidence). Investigators of one study reported improvement in visual acuity, but we could not estimate the effect of adjunctive steroid therapy because the study investigators did not provide any estimates of precision. Only one study examined intraocular pressure (IOP). The evidence suggests that adjunctive dexamethasone may reduce IOP slightly after 12 months of interventions (mean difference -1.90, 95% CI -3.78 to 0.07; 1 study; 167 participants; low certainty evidence). Three studies reported adverse events (retinal detachment, hypotony, proliferative vitreoretinopathy, seclusion of pupil, floaters, and pucker). The total numbers of adverse events were 14 out of 111 (12.6%) for those who received dexamethasone versus 12 out of 116 (10.3%) for those who did not. We could only perform a pooled analysis for the occurrence of retinal detachment: any difference between the two treatment groups was uncertain (RR 1.41, 95% CI 0.53 to 3.74; 227 participants; low certainty evidence). No study reported cost-related outcomes.
AUTHORS' CONCLUSIONS
The currently available evidence on the effectiveness of adjunctive steroid therapy versus antibiotics alone in the management of acute endophthalmitis after intraocular surgery is inadequate. We found no studies that had enrolled cases of acute endophthalmitis following intravitreous injection. A combined analysis of two studies suggests that use of adjunctive steroids may provide a higher chance of having a good visual outcome at three months than not using adjunctive steroids. However, considering that most of the confidence intervals crossed the null, and that this review was limited in scope and applicability to clinical practice, it is not possible to conclude whether the use of adjunctive steroids is effective at this time. Any future trials should examine whether adjunctive steroids may be useful in certain clinical settings such as type of causative organism or etiology. These studies should include outcomes that take patients' symptoms and clinical examination into account; report outcomes in a uniform and consistent manner; and follow up at short- and long-term intervals.
Topics: Anti-Bacterial Agents; Dexamethasone; Endophthalmitis; Eye Diseases; Humans; Retinal Detachment; Steroids
PubMed: 35665485
DOI: 10.1002/14651858.CD012131.pub3 -
Advances in Ophthalmology Practice and... 2022To compare the complications of femtosecond laser-assisted cataract surgery (FLACS) with those of conventional phacoemulsification surgery (CPS) for age-related... (Review)
Review
PURPOSE
To compare the complications of femtosecond laser-assisted cataract surgery (FLACS) with those of conventional phacoemulsification surgery (CPS) for age-related cataracts.
METHODS
PubMed, Cochrane Library, and EMBASE were systematically searched for studies comparing FLACS and CPS. Outcomes were operative complications, including the intraoperative capsule tear, postoperative corneal edema, macular edema, uncontrolled IOP, etc. The effect measures were weighted with odds ratios with 95% CIs.
RESULTS
Nineteen RCTs and 18 cohort studies, including 24,806 eyes (11,375 of the FLACS group and 13,431 of the CPS group), were identified. There were no significant differences between the two groups in anterior capsule tear, corneal edema, macular edema, uncontrolled IOP, vitreous loss, posterior vitreous detachment, etc. Posterior capsule tear rate showed a significantly lower in RCT subgroups ( = 0.04) and without differences in total ( = 0.63). Significant differences were observed in the incidence of descemet membrane tear/trauma ( = 0.02) and IFIS/iris trauma ( = 0.04. Additionally, The FLACS specific complications showed a significantly higher rate of miosis ( < 0.0001), corneal epithelial defect ( = 0.001), corneal haze ( = 0.002), and subconjunctival hemorrhage ( = 0.01).
CONCLUSIONS
FLACS maintains the same safety compared with CPS in terms of all intraoperative and postoperative complications. Although FLACS did show a statistically significant difference for several FLACS specific complications, it would not influence the visual outcome and heal itself.
PubMed: 37846222
DOI: 10.1016/j.aopr.2022.100027 -
Pharmaceuticals (Basel, Switzerland) Aug 2020Bullous central serous chorioretinopathy (bCSCR) is a rare variant of the central serous chorioretinopathy, complicated by an exudative retinal detachment with shifting... (Review)
Review
Bullous central serous chorioretinopathy (bCSCR) is a rare variant of the central serous chorioretinopathy, complicated by an exudative retinal detachment with shifting fluid. This systematic review aims to present the epidemiology, the pathogenesis, the clinical presentation, the imaging, the differential diagnosis, and the latest treatments of this disease. A total of 60 studies were identified following a literature search adhering to PRISMA guidelines. After full-text evaluation, 34 studies about bCSCR were included. bCSCR usually affects middle-aged men, and the principal risk factor is corticosteroid medications. Pathogenesis is related to an increased choroidal vessel and choriocapillaris permeability, with subsequent subretinal fluid accumulation, rich in fibrin, which may provoke the exudative retinal detachment. Clinical presentation and imaging are fundamental to distinguish bCSCR from other pathologies, avoiding unappropriated treatment. Corticosteroid withdraws (if assumed) and laser photocoagulation of leakage sites seen at angiography may speed up retinal reattachment. Verteporfin photodynamic therapy, transpupillary thermal therapy, oral eplerenone and scleral thinning surgery are other therapeutic options. An early diagnosis might prevent disease progression due to harmful medications as well as unnecessary surgery.
PubMed: 32872388
DOI: 10.3390/ph13090221 -
Frontiers in Genetics 2022The inner retina is supplied by three intraretinal capillary plexi whereas the outer retina is supplied by the choroidal circulation: NDP is essential for normal... (Review)
Review
The inner retina is supplied by three intraretinal capillary plexi whereas the outer retina is supplied by the choroidal circulation: NDP is essential for normal intraretinal vascularisation. Pathogenic variants in NDP (Xp11.3) may result in either a severe retinal phenotype associated with hearing loss (Norrie Disease) or a moderate retinal phenotype (Familial Exudative Vitreoretinopathy, FEVR). However, little is known about whether the nature or location of the NDP variant is predictive of severity. In this systematic review we summarise all reported NDP variants and draw conclusions about whether the nature of the NDP variant is predictive of the severity of the resulting ocular pathology and associated hearing loss and intellectual disability. 201 different variants in the NDP gene have been reported as disease-causing. The pathological phenotype that may result from a disease-causing NDP variant is quite diverse but generally comprises a consistent cluster of features (retinal hypovascularisation, exudation, persistent foetal vasculature, tractional/exudative retinal detachment, intellectual disability and hearing loss) that vary predictably with severity. Previous reviews have found no clear pattern in the nature of NDP mutations that cause either FEVR or Norrie disease, with the exception that mutations affecting cysteine residues have been associated with Norrie Disease and that visual loss amongst patients with Norrie disease tends to be more severe if the NDP mutation results in an early termination of translation as opposed to a missense related amino acid change. A key limitation of previous reviews has been variability in the case definition of Norrie disease and FEVR amongst authors. We thus reclassified patients into two groups based only on the severity of their retinal disease. Of the reported pathogenic variants that have been described in more than one patient, we found that any given variant caused an equivalent severity of retinopathy each time it was reported with very few exceptions. We therefore conclude that specific NDP mutations generally result in a consistent retinal phenotype each time they arise. Reports by different authors of the same variant causing either FEVR or Norrie disease conflict primarily due to variability in the authors' respective case definitions rather than true differences in disease severity.
PubMed: 35651932
DOI: 10.3389/fgene.2022.884722 -
Frontiers in Medicine 2022A systematic review and meta-analysis of literature-to-date regarding the effects of combined cataract surgery on outcomes of DMEK.
OBJECTIVE
A systematic review and meta-analysis of literature-to-date regarding the effects of combined cataract surgery on outcomes of DMEK.
METHODS
Multiple electronic databases were searched, including Cochrane Library databases, PubMed, Web of Science, and ClinicalTrials.gov. The final search was updated on 10th February 2022. We included randomized controlled trials (RCTs), non-randomized studies and large case series (≥25 eyes) of DMEK (pseudophakic/phakic) and "triple DMEK". A total of 36 studies were included in this study. Meta-analyses were done with risk differences (RD) computed for dichotomous data and the mean difference (MD) for continuous data via random-effects model. Primary outcome measure: postoperative re-bubbling rate; secondary outcome measures: complete/partial graft detachment rate, best-corrected visual acuity (BCVA), endothelial cell loss (ECL), primary graft failure, and cystoid macular edema (CMO).
RESULTS
A total of 11,401 eyes were included in this review. Based on non-randomized studies, triple DMEK demonstrated a better BCVA at 1-month postoperative than DMEK alone (MD 0.10 logMAR; 95% CI: 0.07-0.13; < 0.001), though not statistically significant at 3-6 months postoperative (MD 0.07 logMAR; 95% CI: -0.01 to 0.15; = 0.08). There was no significant difference in rebubbling, ECL, graft failures, and CMO postoperatively between the two groups ( = 0.07, = 0.40, 0.06, and 0.54 respectively).
CONCLUSION
Our review suggests that DMEK has a similar post-operative complication risk compared to "triple DMEK" (low-quality evidence), with comparable visual outcome and graft survival rate at 6 months postoperative. High-quality RCTs specifically studying the outcomes of combined vs. staged DMEK are still warranted.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020173760, identifier: CRD42020173760.
PubMed: 35425783
DOI: 10.3389/fmed.2022.857200 -
Journal of Pharmacy & Bioallied Sciences Nov 2021Autorotation of the mandible is a normally anticipated phenomenon following a surgical superior repositioning of the maxilla in clinical situations where patients have... (Review)
Review
BACKGROUND
Autorotation of the mandible is a normally anticipated phenomenon following a surgical superior repositioning of the maxilla in clinical situations where patients have an excessive gummy smile. Prediction of the surgical treatment outcome following a presurgical orthodontic treatment is a critical element in the surgical treatment planning.
MATERIALS AND METHODS
The relevant articles were selected by hand search and electronic media (Google Scholar, PubMed, Science Direct, Medline, Embase, and Cochrane) from 1982 to 2020. All the relevant articles were properly screened, and findings were extracted from the articles.
RESULTS
It was observed that, following maxillary intrusion, mandible would eventually autorotate to take a new occlusion. Mandibular autorotation as a result of maxillary intrusion would lead to minimal shortening of the lower lip in the vertical plane. It was observed that the amount of mandibular autorotation correlates with the extent of maxillary impaction. Studies have shown that there is a passive soft-tissue response which may be attributed to the fact that no muscular detachment had been affected in the lower lip and soft-tissue chin region during the maxillary surgery.
CONCLUSION
It is observed that there is a definite influence on the mandibular and chin positions as a result of maxillary intrusion and autorotation of the mandible. Every 1 mm of maxillary superior impaction, the chin moved 0.6 mm vertically and 0.2 mm horizontally. There is an appreciable shortening of the lower lip length.
PubMed: 35017904
DOI: 10.4103/jpbs.jpbs_389_21 -
Ultrasound in Obstetrics & Gynecology :... Sep 2022To determine whether intrapartum transperineal ultrasound measurement of the angle of progression (AoP) during the second stage of labor can predict uncomplicated... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To determine whether intrapartum transperineal ultrasound measurement of the angle of progression (AoP) during the second stage of labor can predict uncomplicated operative vaginal delivery (OVD) using vacuum or forceps extraction.
METHODS
A systematic search in PubMed, EMBASE, Scopus, Web of Science and Google Scholar was performed from inception to February 2021. Studies assessing the predictive accuracy of AoP, measured using intrapartum transperineal ultrasound, for uncomplicated OVD, defined as successful vaginal delivery within three pulls using forceps or no more than two detachments of the vacuum extractor cup, were included. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Summary receiver-operating-characteristics (ROC) curves, pooled sensitivity and specificity, area under the ROC curve (AUC) and summary likelihood ratios (LRs) were calculated.
RESULTS
Seven studies reporting on a total of 782 patients undergoing OVD were included in this systematic review and meta-analysis. Second-stage AoP measured during maternal rest had a pooled sensitivity of 80% (95% CI, 59-92%) and specificity of 89% (95% CI, 76-95%), with a LR+ of 7.3 (95% CI, 3.1-15.8) for uncomplicated OVD. AoP measured during active pushing had a sensitivity of 91% (95% CI, 85-94%) and specificity of 83% (95% CI, 69-92%), with a LR+ of 5.4 (95% CI, 2.7-10.6) for uncomplicated OVD. The performance of AoP measured at rest was particularly high in nulliparous women, with a sensitivity of 87% (95% CI, 75-94%) and specificity of 90% (95% CI, 82-94%) for uncomplicated OVD.
CONCLUSION
AoP may be a reliable predictor for uncomplicated OVD when measured during the second stage of labor, especially in nulliparous women. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Delivery, Obstetric; Female; Humans; Labor Presentation; Labor, Obstetric; Pregnancy; Prospective Studies; ROC Curve; Ultrasonography; Ultrasonography, Prenatal
PubMed: 35238424
DOI: 10.1002/uog.24886 -
Neurology Apr 2022There is currently no consensus about the extent of gray matter (GM) atrophy that can be attributed to secondary changes after white matter (WM) lesions or the temporal...
BACKGROUND AND OBJECTIVES
There is currently no consensus about the extent of gray matter (GM) atrophy that can be attributed to secondary changes after white matter (WM) lesions or the temporal and spatial relationships between the 2 phenomena. Elucidating this interplay will broaden the understanding of the combined inflammatory and neurodegenerative pathophysiology of multiple sclerosis (MS), and separating atrophic changes due to primary and secondary neurodegenerative mechanisms will then be pivotal to properly evaluate treatment effects, especially if these treatments target the different processes individually. To untangle these complex pathologic mechanisms, this systematic review provides an essential first step: an objective and comprehensive overview of the existing in vivo knowledge of the relationship between brain WM lesions and GM atrophy in patients diagnosed with MS. The overall aim was to clarify the extent to which WM lesions are associated with both global and regional GM atrophy and how this may differ in the different disease subtypes.
METHODS
We searched MEDLINE (through PubMed) and Embase for reports containing direct associations between brain GM and WM lesion measures obtained by conventional MRI sequences in patients with clinically isolated syndrome and MS. No restriction was applied for publication date. The quality and risk of bias in included studies were evaluated with the Quality Assessment Tool for observational cohort and cross-sectional studies (NIH, Bethesda, MA). Qualitative and descriptive analyses were performed.
RESULTS
A total of 90 articles were included. WM lesion volumes were related mostly to global, cortical and deep GM volumes, and those significant associations were almost without exception negative, indicating that higher WM lesion volumes were associated with lower GM volumes or lower cortical thicknesses. The most consistent relationship between WM lesions and GM atrophy was seen in early (relapsing) disease and less so in progressive MS.
DISCUSSION
The findings suggest that GM neurodegeneration is mostly secondary to damage in the WM during early disease stages while becoming more detached and dominated by other, possibly primary neurodegenerative disease mechanisms in progressive MS.
Topics: Atrophy; Brain; Cross-Sectional Studies; Gray Matter; Humans; Magnetic Resonance Imaging; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Neoplasm Recurrence, Local; Neurodegenerative Diseases; White Matter
PubMed: 35173016
DOI: 10.1212/WNL.0000000000200006