Long-term Follow-up of Preoperative Infant Event-related Potentials in School-age Children with Craniosynostosis.

BACKGROUND: Previous studies demonstrated impaired auditory processing in children with sagittal and metopic craniosynostosis before surgical correction. This study investigated whether worse presurgical neural response as assessed by event-related potentials (ERP) was predictive of poorer school-age neurocognition. METHODS: Preoperative infant ERP was recorded in 15 sagittal and 18 metopic patients. Mismatch negativity and P150 paradigms were derived from ERP recordings, as previously published. Of those, 13 sagittal and 13 metopic patients returned for neurocognitive evaluation 6 or more years later. ERP was correlated to neurocognitive outcomes using Spearman's correlations controlling for age. Two-tailed t-tests were used to evaluate the influence of age at the time of surgery (6 months) and morphologic severity on neurocognitive outcomes. RESULTS: In the sagittal group, no significant correlations were found between preoperative mismatch negativity or P150 amplitudes and neurocognitive outcomes. Although no correlation was found between mismatch negativity and neurocognitive outcome in the metopic group, those with lower P150 amplitudes had higher scores in performance IQ (r = -0.877, P < 0.001) and full-scale IQ (r = -0.893, P < 0.001). Morphologic severity and neurocognitive outcomes showed no relationship in the sagittal or metopic groups. Patients who received surgery at less than 6 months had higher full-scale IQ (109.69 versus 95.92, P = 0.025), visuomotor integration (103.15 versus 90.46, P = 0.041), and visual perception scores (105.69 versus 96.08, P = 0.033). CONCLUSIONS: Preoperative infant ERP does not correlate with school-age neurocognitive outcomes. Earlier age at the time of surgery was associated with improved neurocognitive outcomes.

Functional Network Development in Sagittal Craniosynostosis Treated With Whole Vault Cranioplasty.

INTRODUCTION: In this study, the authors seek to clarify the neurological changes before and after whole vault cranioplasty (WVC) in patients born with sagittal craniosynostosis. METHODS: A case control study design was performed that included thirty functional MRI scans, from 25 individual patients. Functional MRI and diffusion tension imaging data were analyzed with BioImageSuite (Yale University, USA). 9 functional brain networks were analyzed, with appropriate correlated functional regions of the brain and utilized for analysis. RESULTS: Comparing functional MRI the infants after WVC versus infants before WVC group, the after WVC group demonstrated an increased connectivity in the left frontoparietal, secondary (V2), and third (V3) visual networks (P < 0.001). The right frontoparietal (RFPN) had decreased connectivity (P < 0.001). There is also a decrease and increase in anisotropy in the cingulum and precuneus despite surgery, respectively (P < 0.05). Adolescents treated with WVC compared to controls, demonstrated an increased connectivity in the salience and decreased connectivity in the RFPN relative to adolescent controls. CONCLUSIONS: Patients born with sagittal craniosynostosis have different connections in infancy in most of the defined cerebral networks compared to controls. After surgery, there are specific connectivity changes that occur in the RFPN, left frontoparietal, V2, and V3 networks, which are areas associated with executive function and emotional control. Changes identified in white matter tract microstructure connections could be influential in changes in functional connectivity. Although, as a child with sagittal craniosynostosis develops, much of the abnormal network connections, seen in infancy preoperatively, corrects to some degree after surgery. However, some aberrancies in the salience and RFPN networks remain potentially affecting executive functioning.

Long-Term Neurocognitive Outcomes in Sagittal Synostosis: The Impact of Reoperation.

INTRODUCTION: Optimal age at surgery in nonsyndromic sagittal craniosynostosis continues to be debated. Previous reports suggest that earlier age at whole vault cranioplasty more frequently requires reoperation. It is unknown, however, whether reoperation affects neurocognitive outcome. This study examined the impact of reoperation on neurocognitive outcome in children with nonsyndromic sagittal craniosynostosis using comprehensive neurocognitive testing. METHODS: Forty-seven school-age children (age 5-16 years) with nonsyndromic sagittal craniosynostosis who underwent whole-vault cranioplasty were included in this analysis. Participants were administered a battery of standardized neuropsychological testing to measure neurocognitive outcomes. RESULTS: Thirteen of the 47 participants underwent reoperation (27.7%); 11 out of the 13 reoperations were minor revisions while 2 reoperations were cranioplasties. Reoperation rate was not statistically different between patients who had earlier surgery (at age ≤6 months) versus later surgery (at age >6 months) (P > 0.05). Nonreoperated patients who had only one later-in-life surgery did not perform statistically better than reoperated patients on any outcome measure of neurocognitive function, including IQ, academic achievement, visuomotor integration, executive function, and behavior. Comparing reoperated earlier surgery patients with nonreoperated later surgery patients, reoperated earlier surgery patients had higher full-scale and verbal IQ (P < 0.05), scored higher on word reading, reading comprehension, spelling, numerical operations, and visuomotor integration (P < 0.05), and had fewer indicators of suspected learning disabilities (P < 0.01) compared to nonreoperated later surgery patients. CONCLUSION: Reoperation rate after whole vault cranioplasty was 27.7%, with few cases of repeat cranioplasty (4.2% of all patients). Reoperation was not associated with worse neurocognitive outcome. Reoperated earlier surgery patients in fact performed better in IQ, academic achievement and visuomotor integration when compared to nonreoperated later surgery patients.

Preferences of Transgender and Gender-Nonconforming Persons in Gender-Confirming Surgical Care: A Cross-Sectional Study.

INTRODUCTION: Increased awareness for transgender and gender-nonconforming individuals may lead to increased demand for surgical interventions in gender-confirming care. However, limited literature exists regarding transgender and gender-nonconforming preferences and experiences with medical or surgical care. The authors aim to characterize the medical and surgical care sought by this population, as well as their surgical preferences, motivations, and barriers to care. METHODS: An online questionnaire about opinions and personal experiences with medical and surgical care during gender transition was publicized via regional online social networking forums in Connecticut and surrounding areas catering to transgender communities. RESULTS: Responses were received from 313 participants. Participants were 97% male gender at birth and 92% white with an average (SD) age of 51.6 (13.5) years. Fifty-nine percent identified as male-to-female transgender and 20% as gender nonconforming. Respondents were aware of their gender identity at a mean (SD) age of 9.6 (9.0) years, but did not begin transitioning until a mean (SD) age of 38.9 (20.8) years, with gender-nonconforming respondents choosing to transition at a significantly younger age as compared with transgender respondents (29.8 vs 41.4 years; P = 0.0061, unpaired t test). Only 42% of all respondents, with a significantly greater number of transgender as opposed to gender-nonconforming individuals, had previously met with a physician to discuss transitioning (49% vs 21%, P = 0.002, χ test). Eight percent of the study population had undergone gender confirmation surgery (GCS), 52% were interested in GCS, and 40% were not interested in GCS. Primary motivation for GCS included discomfort in one's current body (28%), and barriers to GCS included cost (40%) and reactions of family (40%), partners (32%), and friends (25%). CONCLUSIONS: Transgender and gender-nonconforming individuals lack medical support for gender transition, with fewer than half of survey respondents reporting a prior meeting with a physician to discuss transitioning. The reported perspectives offer important insight into transgender preferences that should act as the basis of future efforts to improve the efficacy of gender-confirming care.

Significance of Friction and Shear in the Prevention of Contemporary Hospital-acquired Pressure Ulcers.

BACKGROUND: Hospital-acquired pressure ulcers (HAPUs) are largely preventable yet still common occurrences in hospitals. The purpose of the current study is to determine how data from the electronic medical record can be used to better understand and predict HAPU formation over the course of a hospital admission. METHODS: A case-control study on HAPUs was performed over an 8-month period at Yale New Haven Hospital. A Cox regression analysis model analyzed the impact of multiple factors on HAPU development including friction and shear, among other Braden score components. A receiver operating characteristic curve was calculated to determine the sensitivity and specificity of changes in these factors in predicting HAPU development. RESULTS: On a sample of 8,790 admissions, HAPU incidence was 4.2% over the study period (6.3% per annum). The average hospital day for HAPU development was day 15.6 (± 19.3). The Cox regression analysis demonstrated that the volatility of the friction and shear component of Braden scores had a risk ratio of 28.6 (P < 0.01; CI, 14.5-56.4). Volatility in the friction and shear component was the most predictive factor with a high receiver operating characteristic curve area of 0.865 (CI, 0.847-0.882). CONCLUSIONS: Volatility of the friction and shear component of Braden scores appears to be the most significant factor preceding HAPU development at Yale New Haven Hospital. Efforts to place more focus on identifying and reducing volatility of this factor may help decrease HAPU risk for future patients.

An Investigation of Brain Functional Connectivity by Form of Craniosynostosis.

PURPOSE: Long-term neurocognitive sequelae of nonsyndromic craniosynostosis (NSC) patients are just beginning to be clarified. This study uses functional MRI (fMRI) to determine if there is evidence of altered brain functional connectivity in NSC, and whether these aberrations vary by form of synostosis. METHODS: Twenty adolescent participants with surgically treated NSC (10 sagittal synostosis, 5 right unilateral coronal synostosis [UCS], 5 metopic synostosis [MSO]) were individually matched to controls by age, gender, and handedness. A subgroup of MSO was classified as severe metopic synostosis (SMS) based on the endocranial bifrontal angle. Resting state fMRI was acquired in a 3T Siemens TIM Trio scanner (Erlangen, Germany), and data were motion corrected and then analyzed with BioImage Suite (Yale School of Medicine). Resulting group-level t-maps were cluster corrected with nonparametric permutation tests. A region of interest analysis was performed based on the left Brodmann's Areas 7, 39, and 40. RESULTS: Sagittal synostosis had decreased whole-brain intrinsic connectivity compared to controls in the superior parietal lobules and the angular gyrus (P = 0.071). Unilateral coronal synostosis had decreased intrinsic connectivity throughout the prefrontal cortex (P = 0.031). The MSO cohort did not have significant findings on intrinsic connectivity, but the SMS subgroup had significantly decreased connectivity among multiple subcortical structures. CONCLUSION: Sagittal synostosis had decreased connectivity in regions associated with visuomotor integration and attention, while UCS had decreased connectivity in circuits crucial in executive function and cognition. Finally, severity of metopic synostosis may influence the degree of neurocognitive aberration. This study provides data suggestive of long-term sequelae of NSC that varies by suture type, which may underlie different phenotypes of neurocognitive impairment.

What is the Functional Difference Between Sagittal With Metopic and Isolated Sagittal Craniosynotosis?

INTRODUCTION: The purpose of this study is to understand the neurological differences between patients born with combined sagittal and metopic craniosynostosis (SMc) and isolated sagittal craniosynostosis (ISc) by studying aberrations in functional brain connectivity and white matter microstructure, before surgery, utilizing functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI). METHODS: The authors collected DTI and resting-state (ie, no sedation and asleep) functional connectivity MRI data in 10 infant patients preoperatively: 5 in the SMc group (4.3 ±â€Š1 months) and 5 in the ISc group (4.8 ±â€Š1.1 months). Resting state fMRI imaging and DTI data were acquired using a 3-T Siemens Trio MRI system (Erlangen, Germany) while the infant patients slept. fMRI data were corrected for movement using SPM, underwent cerebrospinal fluid and white matter signal regression and further analyzed with BioImageSuite. For the DTI data, 3 diffusion runs were averaged, processed utilizing FMRIB Software Library, and analyzed statistically using BioImageSuite. RESULTS: Comparing the SMc versus ISc groups, SMc demonstrated that there was increased connectivity, statistically significant differences, in neural networks between children with sagittal synostosis alone versus those with sagittal with metopic synostosis, in the right BA 31 and BA 23 (corresponding to the posterior cingulate cortex (PCC) (P < 0.001). Analysis of the DTI revealed increased fractional anisotropy (normal maturation of white tracts) in the SMc group in the cingulum compared to the ISc group (P < 0.05). Differences in the functional networks include increased connectivity right frontoparietal network (RFPN) in ISc and increased connectivity in the primary visual network (V1) in SMc (P < 0.001). CONCLUSION: The SMc had increased connectivity as measured by fMR in the PCC, an area associated with attention deficit hyperactivity disorder. The DTI analysis demonstrated an increase in fractional anisotropy of the cingulum in the SMc group, a white matter tract projecting from the cingulate cortex; connections of the limbic (emotional regulation) system are instrumental. In SMc, increase of connectivity in the PCC correlates with an increase in maturation of the cingulum compared to ISc. There is increased connectivity of the RFPN network in the ISc and increased connectivity of the V1 network in the SMc patients. The SMc group has increased connectivity in the PCC, the original seed of the DMN network, and decreased connectivity to the RFPN network. The pattern of increased connectivity in the area of the DMN and decreased connectivity in the RFPN network is similar to the trend when comparing ADHD patients to normal controls. SMc has more similar functional network connectivity to ADHD as compared to ISc.

Understanding the Learning Disabilities Linked to Sagittal Craniosynostosis.

OBJECTIVE: The purpose of this study is to investigate further findings that corroborate similarities between corrected sagittal craniosynostosis and attention deficit hyperactivity disorder (ADHD). The aim is to further characterize the neurocognitive deficits seen in adolescents with corrected craniosynostosis by comparing it to established learning deficits such as ADHD. METHODS: A total of 30 functional magnetic resonance imaging (fMRI) of 10 sagittal nonsyndromic craniosynostosis (sNSC), 10 ADHD-combined, and 10 control adolescents were studied. The fMRI scans were analyzed utilizing Statistical Parametric Mapping (University College London, UK) and analyzed with BioImageSuite (Yale University, New Haven, CT). RESULTS: The ADHD has lower connectivity to Brodmann area (BA) 11 (Montreal Neurological Institution [MNI]: -12,26,-21), BA20 (MNI: 62,-24,-25), and BA21 (MNI: 62,-32,-23) compared to sNSC and controls (P < 0.001). The sNSC has a unique visuospatial defect, compared to ADHD, created by decreased connectivity to BA31 (MNI: -3,-68,37), BA7 (MNI: -4,-68,41), BA19 (MNI: 0,-83,31), visual association cortex (MNI: -4,-78,22), and primary visual cortex (MNI: 7,-74,21) (P < 0.001). CONCLUSION: Patients born with sNSC have different neural connections than children born with ADHD. Patients born with sNSC have decreased connections in areas of visual processing and increased connections in areas of attention and auditory processing than patients with ADHD. Therefore, children with sagittal craniosynsotosis may have learning difficulties that, similar, yet different from ADHD.

Three-dimensional Analysis of How Radiation Affects Deep Inferior Epigastric Perforator (DIEP) Flap Volume, Projection, and Position in Breast Cancer Reconstruction.

BACKGROUND: The deep inferior epigastric perforator (DIEP) flap has gained popularity for autologous free flap breast reconstruction. Historically, patients receiving post mastectomy radiation therapy (PMRT) were not candidates for immediate autologous reconstruction due to concerns for flap volume depletion, fat necrosis, and flap failure. However, this literature is anecdotal and lacks case controls. We objectively analyzed the effects radiation imparts on immediate DIEP flap reconstruction using 3-dimensional software and inherent controls. METHODS: We performed a cohort study on breast cancer patients who underwent immediate bilateral DIEP flap reconstructions followed by PMRT between 2005 and 2014. Exclusion criteria included patients less than 6 months from PMRT completion and bilateral PMRT. Three-dimensional photographs were analyzed using Geomagic (Rock Hill, SC) software to compare flap position, projection, and volume between the irradiated and nonirradiated reconstructed breasts. Breast Q survey evaluated patients' satisfaction. RESULTS: Eleven patients met inclusion criteria. Average time from PMRT completion to photo acquisition was 1.93 years. There was no statistical difference in average volume or projection in the irradiated versus nonirradiated side (P = 0.087 and P = 0.176, respectively). However, position of the irradiated flaps was significantly higher on the chest wall compared to controls (mean difference, 1.325 cm; P < 0.004). CONCLUSIONS: Three-dimensional analysis exhibited no statistical differences in projection or volume between irradiated DIEP flaps and nonirradiated controls. However, irradiated DIEP flaps were positioned higher on the chest wall, similar to observations in irradiated tissue expanders/implants. Patients were satisfied as measured by Breast Q. Immediate bilateral DIEP flap reconstructions can safely be performed with PMRT with satisfactory results.

Normalization of Speech Processing After Whole-Vault Cranioplasty in Sagittal Synostosis.

BACKGROUND: Neurocognitive studies have found impairments in language-related abilities in nonsyndromic craniosynostosis, highlighting clinical importance of early language processing. In this study, neural response to speech sounds in infants with nonsyndromic sagittal craniosynostosis (NSC) is compared, preoperatively and postoperatively, using event-related potentials (ERPs) to objectively characterize development in language processing. METHODS: Electroencephalogram was recorded while 39 infants (12 NSC and 27 controls; ages 73-283 days) listened to the Hindi dental /(Equation is included in full-text article.)a/ and retroflex /da/ phonemes (non-native phonemic discrimination task). The mismatch negativity (MMN) ERP was extracted as the peak amplitude of the largest negative deflection in the difference wave over 80 to 300 milliseconds poststimulus. Differences in MMN were analyzed using repeated measures analysis of variance. RESULTS: The MMN amplitude was attenuated in the infants with NSC preoperatively compared with controls (P = 0.047). A significant region by group interaction (P = 0.045) was observed, and infants with NSC displayed attenuated MMN in the frontal electrodes compared with controls (P = 0.010). Comparing the preoperative and postoperative MMN, a time by group interaction trend (P = 0.070) was observed. Pair-wise comparisons showed a trend for increase in MMN amplitude from preoperatively to postoperatively in the infants with NSC (P = 0.059). At the postoperative time point, infants with NSC showed no significant difference in MMN from controls (P = 0.344). CONCLUSION: Infants with NSC demonstrated atypical neural response to language preoperatively. After undergoing surgery, infants with NSC showed increased MMN amplitude which was not significantly different from controls. These findings support the idea that whole vault cranioplasty may improve neurocognitive outcomes in sagittal craniosynostosis.

The Hand Surgeon Consultation Improves Patient Knowledge in a Hand Surgery Mission to Honduras.

BACKGROUND: The purpose of this study was to assess impact of the surgeon consultation and informed consent process on patient education in an international hand surgery mission compared with a US academic hand surgery practice. These two groups were selected to evaluate communication difficulties in a surgical mission setting compared with standard of care in a high-income country. METHODS: A multi-part survey was administered to patients presenting to a hand surgery mission during March 2012 and new patients of a university hand center in a 3-month period during 2011. Surveys were administered prior to and following surgeon consultation with one fellowship-trained hand surgeon. The survey assessed knowledge of basic hand anatomy, physiology, disease, individual diagnosis, and surgical risks. RESULTS: 71 patients participated in the study (university n=36, mission n=35). Pre-consultation quiz score averaged 58% in the university group versus 27% in the mission group. Post-consultation quiz scores averaged 62% in the university group versus 40% in the mission group. Only the mission group's quiz score increase was statistically significant. 93% of the university group reported learning about their condition and diagnosis, but only 40% demonstrated correct insight into their diagnosis. In the mission group, 73% reported learning about their condition and diagnosis while 53% demonstrated correct insight into their diagnosis. Although all consultations involved discussion of surgical risks, only 62% of the university group and 52% of the mission group recalled discussing surgical risks. CONCLUSIONS: The hand surgeon consultation was more effective in improving hand knowledge in the surgery mission group compared to in a university hand practice. This suggests that the surgeon consultation should be pursued despite communication barriers in surgical missions. However, the discrepancy between patient perception of knowledge gains and correct insight into diagnosis, and the deficit of patient retention of surgical risks need to be improved.

Functional and Quality of Life Outcomes of a Hand Surgery Mission to Honduras.

Background: The objective of this study was to assess functional, quality of life, and satisfaction outcomes of a hand surgery short-term surgical mission (STSM) to Honduras, and determine whether patient demographics and surgery characteristics during a surgical mission correlate with outcome. Methods: A total of 63 patients who received upper extremity surgery at a week-long hand surgery STSM to Honduras in March 2013 participated in the study. A before-after study design was used. Before receiving surgery, participants completed the Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) questionnaire and the Short Form 12 Health Survey version 2 (SF12v2). Four months postoperatively, participants completed the QuickDASH, SF12v2, and Satisfaction Survey. Results: The mean QuickDASH score significantly improved preoperatively to postoperatively. Demographics measures of age, sex, education, and income did not correlate with QuickDASH scores. Preoperative QuickDASH statistically significantly correlated with surgery type: Carpal tunnel patients had the highest scores (worst functioning). Postoperatively, mass excision and scar contracture/skin graft patients were correlated with the lowest scores. Carpal tunnel and tendon surgery patients showed greatest correlation with QuickDASH improvement. SF-12 scores revealed improvements in mental domains and declines in physical domains. Conclusions: Hand surgery performed during STSMs can result in significant functional improvement, regardless of socioeconomic status. Patients benefited from both simpler and more complex operations. Four months after surgery, general health-related quality of life measures showed improved mental indices. Measured physical indices declined despite improved QuickDASH scores. This may be due to the early general postoperative state. Further outcome research in STSMs in additional countries and specialties is required to expand our conclusions to other STSM contexts and guide best practices in STSMs.

The Etiology of Neuronal Development in Craniosynostosis: A Working Hypothesis.

Craniosynostosis is one of the most common craniofacial conditions treated by neurologic and plastic surgeons. In addition to disfigurement, children with craniosynostosis experience significant cognitive dysfunction later in life. Surgery is performed in infancy to correct skull deformity; however, the field is at a crossroads regarding the best approach for correction. Since the cause of brain dysfunction in these patients has remained uncertain, the role and type of surgery might have in attenuating the later-observed cognitive deficits through impact on the brain has been unclear. Recently, however, advances in imaging such as event-related potentials, diffusion tensor imaging, and functional MRI, in conjunction with more robust clinical studies, are providing important insight into the potential etiologies of brain dysfunction in syndromic and nonsyndromic craniosynostosis patients. This review aims to outline the cause(s) of such brain dysfunction including the role extrinsic vault constriction might have on brain development and the current evidence for an intrinsic modular developmental error in brain development. Illuminating the cause of brain dysfunction will identify the role of surgery can play in improving observed functional deficits and thus direct optimal primary and adjuvant treatment.

Two locus inheritance of non-syndromic midline craniosynostosis via rare SMAD6 and common BMP2 alleles.

Premature fusion of the cranial sutures (craniosynostosis), affecting 1 in 2000 newborns, is treated surgically in infancy to prevent adverse neurologic outcomes. To identify mutations contributing to common non-syndromic midline (sagittal and metopic) craniosynostosis, we performed exome sequencing of 132 parent-offspring trios and 59 additional probands. Thirteen probands (7%) had damaging de novo or rare transmitted mutations in SMAD6, an inhibitor of BMP - induced osteoblast differentiation (p<10-20). SMAD6 mutations nonetheless showed striking incomplete penetrance (<60%). Genotypes of a common variant near BMP2 that is strongly associated with midline craniosynostosis explained nearly all the phenotypic variation in these kindreds, with highly significant evidence of genetic interaction between these loci via both association and analysis of linkage. This epistatic interaction of rare and common variants defines the most frequent cause of midline craniosynostosis and has implications for the genetic basis of other diseases.

The effect of aromatase inhibition on the cognitive function of older patients with breast cancer.

INTRODUCTION: This study evaluated the association between aromatase inhibitor (AI) therapy and cognitive function (over a 6-month period) in a cohort of patients aged ≥ 60 years compared with an age-matched healthy control group, and it evaluated changes in regional cerebral metabolism as measured by positron emission tomography (PET) scans of the brain done in a subset of the patient cohort. PATIENTS AND METHODS: Thirty-five patients (32 evaluable) and 35 healthy controls were recruited to this study. Patients with breast cancer completed a neuropsychological battery, self-reported memory questionnaire, and geriatric assessment before initiation of AI therapy and again 6 months later. Age-matched healthy control participants completed the same assessments at the same time points as the patient group. RESULTS: No significant decline in cognitive function was seen among individuals receiving an AI from pretreatment to 6 months later compared with healthy controls. In the PET cohort over the same period, both standardized volume of interest and statistical parametric mapping analyses detected specific changes in metabolic activity between baseline and follow-up uniquely in the AI patients, most significantly in the medial temporal lobes. CONCLUSION: Although patients undergoing AI treatment had few changes in neuropsychological performance compared with healthy controls over a 6-month period, regionally specific changes in cerebral metabolic activity were identified during this interval in the patient group. Additional longitudinal follow-up is needed to understand the potential clinical implications of these findings.