A Novel Macroglossia Severity Index for Beckwith-Wiedemann Syndrome.

OBJECTIVE/ SUMMARY BACKGROUND DATA: We propose the first classification scheme for macroglossia in patients with Beckwith-Wiedemann Syndrome (BWS), the BWS Index of macroGlossia (BIG). METHODS: Patients with molecularly confirmed BWS seen from 2004-2023 were included to develop this system. Relationships among BIG scores, tongue reduction surgery, BWS clinical score, percent mosaicism, and polysomnography findings were examined. RESULTS: Patients were classified from BIG0 to BIG3. BIG0 includes those without macroglossia; BIG1 includes those with macroglossia not protruding beyond the teeth/alveolus; BIG2 includes those with tongue protrusion past the teeth/alveolus to the lips but that can be contained within the mouth; and BIG3 includes those with tongues that protrude beyond the teeth/alveolus and lips but that cannot be closed within the mouth. Of the 459 patients with molecularly confirmed BWS, 266 (58.0%) patients were scored. One hundred and eleven (41.7%) were BIG0, 44 (16.5%) were BIG1, 90 (33.8%) were BIG2, and 21 (7.9%) were BIG3. As scores increased, patients had an increased incidence of tongue reduction surgery (BIG0: 0% versus BIG1: 20.5% versus BIG2: 51.1% versus BIG3: 100%; r=0.66, P <0.01). Higher BIG scores were associated with elevated BWS clinical scores (r=0.68, P <0.01) and increased tissue mosaicism (r=0.50, P <0.01) as well as trends towards worse obstructive apnea-hypopnea indices (r=0.29, P =0.02) and lower SpO 2 nadirs (r=-0.29, P =0.02). CONCLUSION: In this large series of patients with Beckwith-Wiedemann Syndrome, increased BIG score correlates with undergoing tongue reduction surgery and increased phenotypic severity. Adoption of the BIG scoring system may facilitate communication and risk stratification across institutions.

Columbia-Suicide Severity Rating Scale (C-SSRS) Reveals High Rates of Suicidality in 602 Patients With Cleft and Craniofacial Conditions.

INTRODUCTION: Little is known about rates of suicidal ideation and behavior among youth with cleft lip and/or palate (CLP) and other craniofacial conditions. METHODS: Records of patients ages 6 and older who were administered the Columbia-Suicide Severity Rating Scale (C-SSRS) Lifetime Version during routine multidisciplinary cleft or craniofacial team visits between 2019 and 2023 were examined. Demographics information, C-SSRS data, and diagnoses were assessed with statistics including t tests, the Fisher exact test, and odds ratios. RESULTS: A total of 1140 C-SSRS questionnaires across 602 (433 CLP and 169 craniofacial) patients with an average age of 11.2±3.7 years were included. Eighty-four (13.6%) patients endorsed lifetime suicidal ideation, 9 (1.5%) had at least one instance of suicidal behavior, 30 (5.0%) endorsed nonsuicidal self-injury, and 2 (0.3%) engaged in self-injurious behavior. Compared with CLP, those with other craniofacial conditions had similar odds of endorsing suicidal ideation and behavior ( P ≥0.05). Compared with those with isolated cleft palates, CLP had greater odds of endorsing suicidal ideation and behavior, though those differences were not significant ( P ≥0.05). Incidence of suicidality was unchanged before, during, and after the COVID-19 pandemic ( P ≥0.05). Dividing patients by sex or insurance type revealed no difference in suicidality ( P ≥0.05). CONCLUSION: Patients with CLP and craniofacial conditions have a high incidence of suicidal ideation and behavior, though levels are similar between these groups. Suicidality in these patients was not negatively impacted by the COVID-19 pandemic. Early identification of safety risks and psychosocial challenges through regular screening can facilitate connection with appropriate clinical interventions.

The Timing of Acute and Late Complications Following Mastectomy and Implant-based Reconstruction.

BACKGROUND/OBJECTIVE: Implant-based breast reconstruction is a common plastic surgery procedure with well-documented clinical outcomes. Despite this, the natural history and timing of key complication endpoints are not well described. The goal of this study is to determine when patients are most likely to experience specific adverse events after implant-based reconstruction. METHODS: Retrospective consecutive series of patients who received mastectomy and implant-based reconstruction over a 6-year period were included. Complications and unfavorable outcomes including hematoma, seroma, wound infection, skin flap necrosis, capsular contracture, implant rippling, and implant loss were identified. A time-to-event analysis was performed and Cox regression models identified patient and treatment characteristics associated with each outcome. RESULTS: Of 1473 patients and 2434 total reconstructed breasts, 785 complications/unfavorable outcomes were identified. The 12-month cumulative incidence of hematoma was 1.4%, seroma: 4.3%, infection: 3.2%, skin flap necrosis: 3.9%, capsular contracture: 5.7%, implant rippling: 7.1%, and implant loss: 3.9%. In the analysis, 332/785 (42.3%) complications occurred within 60 days of surgery; 94% of hematomas, 85% of skin necrosis events, and 75% of seromas occurred during this period. Half of all infections and implant losses also occurred within 60 days. Of the remaining complications, 94% of capsular contractures and 93% of implant rippling occurred >60 days from surgery. CONCLUSIONS: Complications following mastectomy and implant-based reconstruction exhibit a discrete temporal distribution. These data represent the first comprehensive study of the timing of adverse events following implant-based reconstruction. These findings are immediately useful to guide postoperative care, follow-up, and clinical trial design.

An Irf6-Esrp1/2 regulatory axis controls midface morphogenesis in vertebrates.

Irf6 and Esrp1 are important for palate development across vertebrates. In zebrafish, we found that irf6 regulates the expression of esrp1 We detailed overlapping Irf6 and Esrp1/2 expression in mouse orofacial epithelium. In zebrafish, irf6 and esrp1/2 share expression in periderm, frontonasal ectoderm and oral epithelium. Genetic disruption of irf6 and esrp1/2 in zebrafish resulted in cleft of the anterior neurocranium. The esrp1/2 mutant also developed cleft of the mouth opening. Lineage tracing of cranial neural crest cells revealed that the cleft resulted not from migration defect, but from impaired chondrogenesis. Analysis of aberrant cells within the cleft revealed expression of sox10, col1a1 and irf6, and these cells were adjacent to krt4+ and krt5+ cells. Breeding of mouse Irf6; Esrp1; Esrp2 compound mutants suggested genetic interaction, as the triple homozygote and the Irf6; Esrp1 double homozygote were not observed. Further, Irf6 heterozygosity reduced Esrp1/2 cleft severity. These studies highlight the complementary analysis of Irf6 and Esrp1/2 in mouse and zebrafish, and identify a unique aberrant cell population in zebrafish expressing sox10, col1a1 and irf6 Future work characterizing this cell population will yield additional insight into cleft pathogenesis.

FaceBase 3: analytical tools and FAIR resources for craniofacial and dental research.

The FaceBase Consortium was established by the National Institute of Dental and Craniofacial Research in 2009 as a 'big data' resource for the craniofacial research community. Over the past decade, researchers have deposited hundreds of annotated and curated datasets on both normal and disordered craniofacial development in FaceBase, all freely available to the research community on the FaceBase Hub website. The Hub has developed numerous visualization and analysis tools designed to promote integration of multidisciplinary data while remaining dedicated to the FAIR principles of data management (findability, accessibility, interoperability and reusability) and providing a faceted search infrastructure for locating desired data efficiently. Summaries of the datasets generated by the FaceBase projects from 2014 to 2019 are provided here. FaceBase 3 now welcomes contributions of data on craniofacial and dental development in humans, model organisms and cell lines. Collectively, the FaceBase Consortium, along with other NIH-supported data resources, provide a continuously growing, dynamic and current resource for the scientific community while improving data reproducibility and fulfilling data sharing requirements.

Precise differentiation between jugular foramen paragangliomas and metastases: utility of diffusion-weighted and dynamic contrast-enhanced magnetic resonance imaging.

PURPOSE: This study tested the utility of diffusion-weighted imaging (DWI) and dynamic contrast-enhanced imaging (DCE-MRI) in differentiating paragangliomas and metastases in the jugular foramen in combination with conventional imaging. METHODS: Forty-nine consecutive patients with paragangliomas or metastases between January 2015 and April 2022 were included in this retrospective study. All patients had pretreatment DWI and DCE-MRI. Between paragangliomas and metastases, normalized apparent diffusion coefficient (nADCmean) and DCE-MRI parameters were compared along with conventional imaging features (enhancement pattern, presence of flow voids, cystic/necrotic change, and bone erosion). The diagnostic performance was tested using receiver operating characteristic (ROC) analysis. RESULTS: Thirty-five paragangliomas (5 male; median 49 years) and 14 metastases (9 male; median 61 years) were analyzed. The most common 3 primary cancers included 4 lung cancers, 3 breast cancers, and 3 melanomas. The presence of flow void was significantly different between paragangliomas and metastases (21/35 vs 2/14; P = 0.0047) in conventional imaging features, while fractional plasma volume (Vp) was significantly different between the two tumor types (median 0.46 vs 0.19; P < 0.001) in DWI and DCE-MRI parameters. The areas under the ROC curves (AUCs) of the presence of flow void and Vp were 0.72 and 0.93, respectively. The AUC of the combination of the presence of flow void and Vp was 0.95 and significantly improved compared to that of the presence of flow void (P < 0.001). CONCLUSION: Adding DCE-MRI to the head and neck protocol can aid in the precise differentiation between jugular foramen paragangliomas and metastases.

MRI Diagnosis of Clival Cancer and Sixth Nerve Palsy.

BACKGROUND: Imaging diagnosis of clival cancer may be difficult, in part because of normal variation in marrow signal with aging. Identifying whether clival cancer has damaged the sixth cranial nerve is a further challenge because minimal clival abnormalities could impinge on the nerve, which travels very close to the clivus. METHODS: Two neuroradiologists, who were unaware of previous imaging and clinical diagnoses, reviewed MRI studies of 25 patients with cancer but no clival involvement and no sixth nerve palsy, 24 patients with clival cancer but without sixth nerve palsy, and 31 patients with clival cancer and sixth nerve palsy. The radiologists were tasked with determining whether there was clival cancer, whether there was a sixth nerve palsy and its laterality, and with indicating the pulse sequences used to make those determinations. RESULTS: Both neuroradiologists correctly identified all 25 cases with a normal clivus. In about half of those cases, they depended on finding a homogeneously bright marrow signal; in the remaining cases, they excluded cancer by determining that the clivus was not expanded and that there were no focal signal abnormalities. Both neuroradiologists correctly identified clival cancer in 54 (98%) of the 55 cases with and without sixth nerve palsy. In doing so, they relied mostly on clival expansion but also on focal signal abnormalities. Both neuroradiologists were at least 80% correct in identifying a sixth nerve palsy, but they often incorrectly identified a palsy in patients who did not have one. When there was a one-sided signal abnormality or the clivus was expanded in one direction, both neuroradiologists were accurate in identifying the side of the sixth nerve palsy. CONCLUSION: Current MRI pulse sequences allow accurate differentiation of a normal from a cancerous clivus. When the marrow signal is not homogeneously bright in adults, cancer can be diagnosed on the basis of clival expansion or focal signal abnormalities. MRI is less accurate in predicting the presence of a sixth nerve palsy. However, the side of a unilateral palsy can be predicted when the clivus is clearly expanded in one direction or there is a focal signal abnormality on one side.

Nasal Construction in Congenital Arhinia Due to Novel SMCHD1 Gene Variant.

Arhinia, or congenital absence of the nose, is an exceedingly rare anomaly caused by pathogenic variants in the gene SMCHD1 . Arhinia exhibits unique reconstructive challenges, as the midface is deficient in skeletal and soft tissue structures. The authors present 2 related patients with arhinia who harbor a novel SMCHD1 gene variant and illustrate their surgical midface and nasal construction. Targeted sequencing was carried out on DNA samples from the 2 affected patients, 1 anosmic and 1 healthy parent, to identify variants in exons 3 to 13 of SMCHD1 . The affected patients and anosmic parent were found to have a novel SMCHD1 gene variant p.E473V. A staged surgical approach was applied. First, both patients underwent a LeFort II osteotomy and distraction osteogenesis to improve the projection of the midfacial segment, followed by tissue expansion of the forehead, and nasal construction with a forehead flap that was placed over a costochondral framework derived from rib cartilage. The novel gene variant could guide future investigations on genetic pathways and molecular processes that underly the physiological and pathologic development of the nose. Further investigations on the variable expressivity ranging from anosmia to arhinia could improve clinical genetic screens for risk stratification of individuals with anosmia on passing on arhinia to their children. Due to the exceptional rarity and complexity of congenital arhinia, most surgical approaches are developed on a single-case basis. This case series, albeit limited to 2 cases, is the largest pedigree of such cases in the literature. It highlights key principles of a staged approach to nasal construction in arhinia and discusses nuances and improvements learned between both patients. It subsequently offers an optimized guide to this surgical strategy.

One-Year Experience of Same-Day Mastectomy and Breast Reconstruction Protocol.

BACKGROUND: The prevalence of same-day mastectomy with reconstruction has continued to increase across the United States in recent years. Prior studies have shown that same-day mastectomy with reconstruction leads to increased patient satisfaction and allows hospitals to use resources better. This study sought to evaluate the implementation of same-day mastectomy with a reconstruction recovery protocol for patients undergoing mastectomy at our institution. METHODS: Under an institutional review board-approved protocol, a retrospective cohort analysis compared patients who underwent mastectomy April 2016 through April 2017 with those who had mastectomy March 2020 through March 2021. Length of stay, postoperative intravenous (IV) opioid administration, safety end points, and cost were the main variables examined. RESULTS: The study compared 457 patients in 2016-2017 with 428 patients in 2020-2021. The median hospital length of stay decreased from 24.6 h in 2016-2017 to 5.5 h in 2020-2021 (p < 0.001). The percentage of patients requiring postoperative IV opioids decreased from 69.1 % in 2016-2017 to 50 % in 2020-2021 (p < 0.001). The rates of unplanned readmissions within 30 days after mastectomy did not differ between the two groups, with a rate of 3.7 % in 2016-2017 and a rate of 5.1 % in 2020-2021 (p = 0.30). Reducing the rate of overnight admissions after mastectomy by 65.8 % resulted in a cost reduction of 65.8 %. CONCLUSIONS: Implementation of same-day mastectomy with a reconstruction protocol across a large academic center and two satellite sites was a safe alternative to conventional mastectomy recovery plans.

Headache neuroimaging: A survey of current practice, barriers, and facilitators to optimal use.

OBJECTIVE: The objective of this study was to understand current practice, clinician understanding, attitudes, barriers, and facilitators to optimal headache neuroimaging practices. BACKGROUND: Headaches are common in adults, and neuroimaging for these patients is common, costly, and increasing. Although guidelines recommend against routine headache neuroimaging in low-risk scenarios, guideline-discordant neuroimaging is still frequently performed. METHODS: We administered a 60-item survey to headache clinicians at the Veterans Affairs health system to assess clinician understanding and attitudes on headache neuroimaging and to determine neuroimaging practice patterns for three scenarios describing hypothetical patients with headaches. Descriptive statistics were used to summarize responses, stratified by clinician type (physicians or advanced practice clinicians [APCs]) and specialty (neurology or primary care). RESULTS: The survey was successfully completed by 431 of 1426 clinicians (30.2% response rate). Overall, 317 of 429 (73.9%) believed neuroimaging was overused for patients with headaches. However, clinicians would utilize neuroimaging a mean (SD) 30.9% (31.7) of the time in a low-risk scenario without red flags, and a mean 67.1% (31.9) of the time in the presence of minor red flags. Clinicians had stronger beliefs in the potential benefits (268/429, 62.5%) of neuroimaging compared to harms (181/429, 42.2%) and more clinicians were bothered by harms stemming from the omission of neuroimaging (377/426, 88.5%) compared to commission (329/424, 77.6%). Additionally, APCs utilized neuroimaging more frequently than physicians and were more receptive to potential interventions to improve neuroimaging utilization. CONCLUSIONS: Although a majority of clinicians believed neuroimaging was overused for patients with headaches, many would utilize neuroimaging in low-risk scenarios with a small probability of changing management. Future studies are needed to define the role of currently used red flags given their importance in neuroimaging decisions. Importantly, APCs may be an ideal target for future optimization efforts.

Major Changes in 2021 World Health Organization Classification of Central Nervous System Tumors.

The World Health Organization (WHO) published the fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5) in 2021, as an update of the WHO central nervous system (CNS) classification system published in 2016. WHO CNS5 was drafted on the basis of recommendations from the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) and expounds the classification scheme of the previous edition, which emphasized the importance of genetic and molecular changes in the characteristics of CNS tumors. Multiple newly recognized tumor types, including those for which there is limited knowledge regarding neuroimaging features, are detailed in WHO CNS5. The authors describe the major changes introduced in WHO CNS5, including revisions to tumor nomenclature. For example, WHO grade IV tumors in the fourth edition are equivalent to CNS WHO grade 4 tumors in the fifth edition, and diffuse midline glioma, H3 K27M-mutant, is equivalent to midline glioma, H3 K27-altered. With regard to tumor typing, isocitrate dehydrogenase (IDH)-mutant glioblastoma has been modified to IDH-mutant astrocytoma. In tumor grading, IDH-mutant astrocytomas are now graded according to the presence or absence of homozygous CDKN2A/B deletion. Moreover, the molecular mechanisms of tumorigenesis, as well as the clinical characteristics and imaging features of the tumor types newly recognized in WHO CNS5, are summarized. Given that WHO CNS5 has become the foundation for daily practice, radiologists need to be familiar with this new edition of the WHO CNS tumor classification system. Online supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article. ©RSNA, 2022.

Visual Field Defect Patterns Associated With Lesions of the Retrochiasmal Visual Pathway.

BACKGROUND: Perimetry is widely used in the localization of retrochiasmal visual pathway lesions. Although macular sparing, homonymous paracentral scotomas, and quadrantanopias are regarded as features of posterior retrochiasmal visual pathway lesions, incongruous hemianopia is regarded as a hallmark of anterior lesions. Recent studies have questioned the specificity of these defect patterns. METHODS: Retrospective record review conducted in a single, academic, medical center using an electronic search engine with the terms ""homonymous hemianopia," "optic tract," "temporal lobectomy," "visual field defect," and "MRI." Patients were included if they had reliable, automated, static visual fields, high-quality reviewable MRI scans, and pertinent lesions. MRI lesions were assigned to 1 of 6 retrochiasmal visual pathway segments by the study neuroradiologist. Two study authors independently reviewed the visual fields and designated 10 different defect patterns. RESULTS: From an original cohort of 256 cases, only 83 had MRI-defined lesions that were limited to particular retrochiasmal segments and had visual field defect patterns that allegedly permitted localization to those particular segments. The 5 contralateral nerve fiber bundle defects were exclusive to optic tract tumors with rostral extension. Pie-in-the-sky defects were exclusive to Meyer loop lesions. Among 22 fields with macular sparing, 86% arose from the visual cortex or posterior optic radiations. Among 31 fields with homonymous quadrantanopias, 77% arose from Meyer loop, visual cortex, or posterior optic radiations. Among 13 fields with homonymous paracentral scotomas, 69% arose from visual cortex or posterior optic radiations. Optic tract lesions accounted for 70% of incongruous hemianopias but that pattern occurred uncommonly. CONCLUSION: In correlating discrete MRI-defined retrochiasmal lesions with visual field defect patterns identified on static perimetry, this study showed that macular sparing, homonymous paracentral scotomas, and quadrantanopias localized to the visual cortex and posterior optic radiations segments but not exclusively. It has differed from an earlier study in showing that incongruous hemianopias occur predominantly from optic tract lesions.

Accuracy of Visual Fields in Localizing MRI Lesions in Posterior Cerebral Artery Infarction.

BACKGROUND: The representation of the visual field in visual cortex was established over a century ago by correlating perimetric defects with the estimated location of war wounds. The availability of high-definition MRI offers the possibility of more precise correlation. METHODS: Homonymous hemianopias disclosed on automated visual fields (HVFs) were drawn from an electronic medical record search from 2009 to 2020 at the Michigan Medicine, a tertiary care academic medical center. The patterns of the visual field defects (VFDs) were interpreted by a consensus of 2 authors. The VFDs were correlated with the location of MRI lesions in 92 patients with posterior cerebral artery (PCA) domain ischemic strokes, as determined by the neuroradiologist author, who was masked as to the VFDs. RESULTS: Among the 77 VFDs confined to 1 hemifield, 74 (96%) correctly predicted the side of the visual cortex lesion. In 3 cases, the MRI lesion in the opposite cerebral hemisphere was not foretold. Among the 15 VFDs present in both hemifields, 5 (33.3%) overestimated the MRI lesions, which were evident in only 1 hemisphere. Among the 30 VFDs confined to 1 quadrant, 29 (97%) correctly predicted the lesioned visual cortex quadrant. However, 14 VFDs failed to predict MRI lesions present in both superior and inferior visual cortex quadrants on the same side. Those unpredicted lesions mostly had subtle or indistinct signal abnormalities or were confined to anterior visual cortex, an area that is inaccessible with the HVF test protocol used in this study. CONCLUSION: In this study of PCA ischemic stroke, VFDs limited to 1 hemifield were accurate in locating the side and quadrant of the MRI visual cortex lesions. However, the quadrantic VFDs sometimes failed to predict that the lesions involved both the superior and inferior quadrants on the same side, largely because those lesions had subtle imaging features that defied accurate radiologic assessment or were out of the reach of the visual field test protocol.

Correlation of Macular Sparing and Homonymous Paracentral Scotomas With MRI Lesions in Posterior Cerebral Artery Infarction.

BACKGROUND: The concepts of the representation of visual field in primary visual cortex are based on studies of war wounds and correlations with brain imaging in small cohorts. Because of the difficulty of judging brain lesion extent and the small number of studied patients, there is lingering controversy as to whether the central 15° of visual field are mapped onto the posterior 25% of primary visual cortex or onto a larger area. To improve the delineation of MRI lesion extent, we have studied only patients with posterior cerebral artery (PCA) ischemic strokes. METHODS: We accrued a cohort of 92 patients with PCA strokes from an electronic medical records search between 2009 and 2020 at a single tertiary care academic institution. Patients had reliable static perimetry demonstrating homonymous hemianopias and high-definition reviewable brain imaging. We divided the primary visual cortex on the MRI T1 sagittal sequence into 8 equal segments in right and left cerebral hemispheres and located lesions according to the segments they occupied. We correlated lesion locations with 3 visual field defects (VFDs): macular-sparing homonymous quadrantanopias, macular-splitting homonymous quadrantanopias, and homonymous paracentral scotomas. RESULTS: Among 25 cases with macular sparing, 13 had lesion-sparing confined to the posterior 25% of visual cortex. Among 6 cases with homonymous paracentral scotomas, 2 had lesions confined to the posterior 25% of visual cortex. Macular-splitting quadrantanopia did not occur in any patients with lesions confined to the posterior 25% of visual cortex, but did occur in 3 patients with lesions confined to the posterior 50% of visual cortex. These phenomena would not be expected if the central 15° of visual field were mapped onto a region extending beyond the posterior 25% of visual cortex. In patients with PCA strokes that involved the retrogeniculate visual pathway proximal to visual cortex, the visual cortex lesions were often less extensive than predicted by the VFDs, perhaps because of widespread damage to axons before they reached their destination in visual cortex. CONCLUSIONS: These results support the concept that the central 15° of the visual field are represented in the posterior 25% of visual cortex. Although this study contributes a larger cohort of patients with better-defined lesion borders than in past reports, its conclusions must be tempered by the variability of patient attention during visual field testing, the subjectivity in the interpretation of the defect patterns, and the difficulty in judging MRI lesion extent even on diffusion-weighted and precontrast T1 sagittal sequences.

The TFAP2A-IRF6-GRHL3 genetic pathway is conserved in neurulation.

Mutations in IRF6, TFAP2A and GRHL3 cause orofacial clefting syndromes in humans. However, Tfap2a and Grhl3 are also required for neurulation in mice. Here, we found that homeostasis of Irf6 is also required for development of the neural tube and associated structures. Over-expression of Irf6 caused exencephaly, a rostral neural tube defect, through suppression of Tfap2a and Grhl3 expression. Conversely, loss of Irf6 function caused a curly tail and coincided with a reduction of Tfap2a and Grhl3 expression in tail tissues. To test whether Irf6 function in neurulation was conserved, we sequenced samples obtained from human cases of spina bifida and anencephaly. We found two likely disease-causing variants in two samples from patients with spina bifida. Overall, these data suggest that the Tfap2a-Irf6-Grhl3 genetic pathway is shared by two embryologically distinct morphogenetic events that previously were considered independent during mammalian development. In addition, these data suggest new candidates to delineate the genetic architecture of neural tube defects and new therapeutic targets to prevent this common birth defect.

Postmastectomy Radiation Therapy on Permanent Implants or Tissue Expanders: Which is Better?

OBJECTIVES: This study evaluates complications and reconstructive failure rates in implant-based reconstruction with radiotherapy. BACKGROUND: Postmastectomy radiotherapy may adversely affect breast reconstructive outcomes. However, the comparative effect of radiotherapy on direct-to-implant versus tissue expander-implant reconstruction has not been examined. METHODS: Single institution retrospective review was performed and patients were followed 2 to 10 years. RESULTS: Of 1566 patients, 265 patients received radiation (149 immediate implants and 116 tissue expanders). Demographics were similar except more smokers in the expander group (7.7% vs 1.3%; P = 0.012). Patients who received radiation with an expander in place had overall more complications (32.8% vs 11.4%; P < 0.001), skin necrosis (10.3% vs 4.0%; P = 0.043), wound breakdown (9.5% vs 2.7%; P = 0.029), and infections (16.4% vs 4.03%; P = 0.001) leading to a higher rate of explantation (16.4% vs 4.0%; P < 0.001). A radiation boost likewise predicted complications [odds ratio (OR) 2.199, 95% confidence interval (CI) 1.154-4.188, P = 0.017]. When comparing reconstructive outcomes, radiated expanders had a higher failure rate (21.6% vs 11.4%; P = 0.025). Revision for capsular contracture was similar between the 2 cohorts (11.4% vs 11.2%; P = 0.959) as were revision rates for contour asymmetry and breast asymmetry. In our multivariable logistic regression analysis, radiation to the expander had a higher risk of reconstruction failure than radiation to the permanent implant (OR 2.020, 95% CI 1.010-4.037, P = 0.047). CONCLUSION: Most patients had successful implant-based reconstructions after mastectomy and radiotherapy. Our study showed radiotherapy after direct-to-implant breast reconstruction had a lower rate of complications and reconstructive failure compared to tissue expander-implant reconstruction.

Target coverage and cardiopulmonary sparing with the updated ESTRO-ACROP contouring guidelines for postmastectomy radiation therapy after breast reconstruction: a treatment planning study using VMAT and proton PBS techniques.

BACKGROUND: The European Society for Therapeutic Radiology and Oncology Advisory Committee in Radiation Oncology Practice (ESTRO-ACROP) recently released new contouring guidelines for postmastectomy radiation therapy (PMRT) after implant-based reconstruction (IBR). As compared to prior ESTRO guidelines, the new guidelines primarily redefined the chest wall (CW) target to exclude the breast prosthesis. In this study, we assessed the impact of these changes on treatment planning and dosimetric outcomes using volumetric-modulated arc therapy (VMAT) and proton pencil-beam scanning (PBS) therapy. METHODS: We performed a treatment planning study of 10 women with left-sided breast cancer who underwent PMRT after IBR. All target structures were delineated first using standard (ESTRO) breast contouring guidelines and then separately using the new (ESTRO-ACROP) guidelines. Standard organs-at-risk (OARs) and cardiac substructures were contoured. Four sets of plans were generated: (1) VMAT using standard ESTRO contours, (2) VMAT using new ESTRO-ACROP contours, (3) PBS using standard contours, and (4) PBS using new contours. RESULTS: VMAT plans using the new ESTRO-ACROP guidelines resulted in modest sparing of the left anterior descending coronary artery (LAD) (mean dose: 6.99 Gy standard ESTRO vs. 6.08 Gy new ESTRO-ACROP, p = 0.010) and ipsilateral lung (V20: 21.66% vs 19.45%, p = 0.017), but similar exposure to the heart (mean dose: 4.6 Gy vs. 4.3 Gy, p = 0.513), with a trend toward higher contralateral lung (V5: 31.0% vs 35.3%, p = 0.331) and CW doses (V5: 31.9% vs 35.4%, p = 0.599). PBS plans using the new guidelines resulted in further sparing of the heart (mean dose: 1.05 Gy(RBE) vs. 0.54 Gy(RBE), p < 0.001), nearly all cardiac substructures (LAD mean dose: 2.01 Gy(RBE) vs. 0.66 Gy(RBE), p < 0.001), and ipsilateral lung (V20: 16.22% vs 6.02%, p < 0.001). CONCLUSIONS: PMRT after IBR using the new ESTRO-ACROP contouring guidelines with both VMAT and PBS therapy is associated with significant changes in exposure to several cardiopulmonary structures.

Dorsal Midbrain Syndrome: Clinical and Imaging Features in 75 Cases.

BACKGROUND: Dorsal midbrain syndrome (DMS) consists of a constellation of clinical features, including reduced upgaze, pupillary light-near dissociation, lid retraction, convergence retraction, and eye misalignment. This syndrome results mostly from intrinsic or extrinsic mesodiencephalic tumors or strokes, obstructive hydrocephalus, failure of cerebrospinal fluid shunting to correct obstructive hydrocephalus, and head trauma. Published reports that include imaging corroboration are based on relatively small cohorts and have not included comprehensive patient self-reports on the impact of these abnormalities on quality of life. METHODS: We conducted a retrospective review of cases of DMS identified between 1998 and 2019 at the University of Michigan using the Electronic Medical Record Search Engine. Patients were included only if they had been evaluated by a neuro-ophthalmologist and had a corroborative imaging abnormality. We collected data on symptoms and on neuro-ophthalmic and neurologic signs. We reviewed brain imaging reports on all 75 patients, and the study neuroradiologist analyzed the imaging in 57 patients. Using a uniform list of questions, we conducted telephone interviews of 26 patients to assess lingering symptoms and their impact on quality of life. RESULTS: There were 75 patients, only 5 of whom were younger than 10 years. Neoplasms accounted for 47%, strokes (mostly thalamic) for 25%, nonneoplastic masses for 12%, nonneoplastic hydrocephalus for 7%, traumatic brain injury for 5%, and demyelination for 4%. Reduced upgaze occurred in 93% of patients, being completely absent or reduced to less than 50% amplitude in 67%. Convergence retraction on attempted upgaze occurred in 52%, horizontal misalignment in 49%, vertical misalignment in 47%, and pupillary light-near dissociation in 37%. Optic neuropathy attributed to chronic papilledema occurred in only 3%. Three or more neuro-ophthalmic signs were present in 84%, and only 4% had a single sign-reduced upgaze. Imaging features did not correlate with the frequency or severity of clinical signs. There was some improvement in the clinical signs among the patients with stroke but no change among the patients with neoplasms. In the 26 telephone interviews, patients with neoplasms reported that imbalance had a greater impact on quality of life than did diplopia. Patients with strokes reported that imbalance had the greatest impact initially but that its effect dissipated. Neither group reported lingering effects of impaired upgaze. CONCLUSIONS: This large series expands on the clinical profile of DMS. Neoplasms and strokes were the most common causes. Obstructive hydrocephalus alone, identified as a major cause in the largest previously published series, was uncommon. At least 3 neuro-ophthalmic signs were present in nearly all patients, with upgaze deficit as predominant. Unlike an earlier report, this study found no correlation between brain imaging and clinical signs. Neuro-ophthalmic signs persisted even after neoplasms were successfully treated and improved only slightly after stroke. Telephone interviews with patients revealed that diplopia and upgaze deficit had less lasting impact on quality of life than did ataxia and concurrent nonneurologic problems.

Assessing the additional surgical risk of contralateral prophylactic mastectomy and immediate breast implant reconstruction.

INTRODUCTION: There has been a sharp rise in the rate of contralateral prophylactic mastectomy over the last decade, despite the low incidence of new primary cancers predicted for the contralateral breast. This study compares the postoperative complication rates between the diseased breast treated with mastectomy and the contralateral breast that underwent prophylactic mastectomy, followed by immediate bilateral breast implant reconstruction. We hypothesized that there will be no difference in postoperative outcomes between prophylactic and diseased groups, as the surgical approach would be comparable. METHODS: After IRB approval, a retrospective chart review identified consecutive unilateral breast cancer patients who underwent bilateral mastectomy and immediate breast reconstruction between May 2008 and May 2018 at a tertiary academic medical center. A paired sample t-test and a penalized logic regression model were constructed to identify relationships between breast laterality and outcomes. RESULTS: A total of 1117 patients with unilateral breast cancer who underwent bilateral mastectomy and immediate breast implant reconstruction were identified. Rates of capsular contracture and infection were significantly greater in the diseased breast, while rates of revision were significantly greater in the contralateral prophylactic breast. There were no statistically significant differences between breasts in rates of explant, skin flap necrosis or hematoma. When adjusted for confounding variables, a higher infection rate was observed in the diseased breast. CONCLUSION: This study detected significant differences in postoperative complication rates between the diseased and prophylactic breasts following bilateral mastectomy and immediate breast implant reconstruction. Postoperative complications occurred more frequently in the diseased breast compared with low rates of complications in the contralateral prophylactic breast. This information is helpful for preoperative decision making, as surgeons and patients carefully weigh the additional risks of contralateral prophylactic procedure.

Meta-analysis of prepectoral implant-based breast reconstruction: guide to patient selection and current outcomes.

PURPOSE:  This meta-analysis provides a large-scale comparison of prepectoral vs. subpectoral implant-based breast reconstruction, with primary outcomes of patient safety and efficacy. METHODS: Literature review was performed via PRISMA criteria, 33 studies met inclusion criteria for prepectoral review and 13 studies met inclusion criteria for meta-analysis. Patient characteristics and per-breast complications were collected. Data were analyzed using Cochrane RevMan and IBM SPSS. RESULTS: In 4692 breasts of 3014 patients that underwent prepectoral breast reconstruction, rippling was observed as the most common complication, followed by seroma and skin flap necrosis. Meta-analysis demonstrated statistically significant decrease in odds of skin flap necrosis and capsular contracture in prepectoral groups compared to subpectoral groups. Odds of infection, seroma, and hematoma were equal between the two groups. CONCLUSIONS: Prepectoral breast reconstruction has surged in popularity in recent years. This review and large-scale analysis corroborates current literature reporting a favorable safety profile with emphasis on patient selection. Variability in skin flap thickness and vascularity mandates thoughtful selection of patients whose overall health and intra-operative skin flap assessment can tolerate a muscle-sparing reconstruction.