SARS-CoV-2 triggers pericyte-mediated cerebral capillary constriction.

The SARS-CoV-2 receptor, ACE2, is found on pericytes, contractile cells enwrapping capillaries that regulate brain, heart and kidney blood flow. ACE2 converts vasoconstricting angiotensin II into vasodilating angiotensin-(1-7). In brain slices from hamster, which has an ACE2 sequence similar to human ACE2, angiotensin II evoked a small pericyte-mediated capillary constriction via AT1 receptors, but evoked a large constriction when the SARS-CoV-2 receptor binding domain (RBD, original Wuhan variant) was present. A mutated non-binding RBD did not potentiate constriction. A similar RBD-potentiated capillary constriction occurred in human cortical slices, and was evoked in hamster brain slices by pseudotyped virions expressing SARS-CoV-2 spike protein. This constriction reflects an RBD-induced decrease in the conversion of angiotensin II to angiotensin-(1-7) mediated by removal of ACE2 from the cell surface membrane and was mimicked by blocking ACE2. The clinically used drug losartan inhibited the RBD-potentiated constriction. Thus, AT1 receptor blockers could be protective in COVID-19 by preventing pericyte-mediated blood flow reductions in the brain, and perhaps the heart and kidney.

Implementation of 3D modelling to improve understanding and conceptualisation of arteriovenous malformation (AVM) morphology for the execution of safe microsurgical excision of complex paediatric AVMs.

INTRODUCTION: Brain arteriovenous malformations (bAVMs) present complex challenges in neurosurgery, requiring precise pre-surgical planning. In this context, 3D printing technology has emerged as a promising tool to aid in understanding bAVM morphology and enhance surgical outcomes, particularly in pediatric patients. This study aims to assess the feasibility and effectiveness of using 3D AVM models in pediatric bAVM surgery. METHODOLOGY: The study was conducted at Great Ormond Street Hospital, and cases were selected sequentially between October 2021 and February 2023. Eight pediatric bAVM cases with 3D models were compared to eight cases treated before the introduction of 3D printing models. The 3D modelling fidelity and clinical outcomes were assessed and compared between the two cohorts. RESULTS: The study demonstrated excellent fidelity between 3D models and actual operative anatomy, with a median difference of only 0.31 mm. There was no statistically significant difference in angiographic cure rates or complications between the 3D model group and the non-3D model group. Surgical time showed a non-significant increase in cases involving 3D models. Furthermore, the 3D model cohort included higher-grade bAVMs, indicating increased surgical confidence. CONCLUSION: This study demonstrates the feasibility and efficacy of utilizing 3D AVM models in pediatric bAVM surgery. The high fidelity between the models and actual operative anatomy suggests that 3D modelling can enhance pre-surgical planning and intraoperative guidance without significantly increasing surgical times or complications. Further research with larger cohorts is warranted to confirm and refine the application of 3D modelling in clinical practice.

Avenues for Strengthening PCORnet's Capacity to Advance Patient-Centered Economic Outcomes in Patient-Centered Outcomes Research (PCOR).

PCORnet, the National Patient-Centered Clinical Research Network, provides the ability to conduct prospective and observational pragmatic research by leveraging standardized, curated electronic health records data together with patient and stakeholder engagement. PCORnet is funded by the Patient-Centered Outcomes Research Institute (PCORI) and is composed of 8 Clinical Research Networks that incorporate at total of 79 health system "sites." As the network developed, linkage to commercial health plans, federal insurance claims, disease registries, and other data resources demonstrated the value in extending the networks infrastructure to provide a more complete representation of patient's health and lived experiences. Initially, PCORnet studies avoided direct economic comparative effectiveness as a topic. However, PCORI's authorizing law was amended in 2019 to allow studies to incorporate patient-centered economic outcomes in primary research aims. With PCORI's expanded scope and PCORnet's phase 3 beginning in January 2022, there are opportunities to strengthen the network's ability to support economic patient-centered outcomes research. This commentary will discuss approaches that have been incorporated to date by the network and point to opportunities for the network to incorporate economic variables for analysis, informed by patient and stakeholder perspectives. Topics addressed include: (1) data linkage infrastructure; (2) commercial health plan partnerships; (3) Medicare and Medicaid linkage; (4) health system billing-based benchmarking; (5) area-level measures; (6) individual-level measures; (7) pharmacy benefits and retail pharmacy data; and (8) the importance of transparency and engagement while addressing the biases inherent in linking real-world data sources.

Paediatric subarachnoid haemorrhage and severe vasospasm secondary to traumatic pseudoaneurysm of a fenestrated vertebral artery: a case report and review of the literature.

Paediatric intracranial aneurysms are rare entities accounting for less than 5% of all age intracranial aneurysms. Traumatic aneurysms are more common in children and have an association with anatomical variations such as arterial fenestrations. Here, we present a case of a child initially presenting with traumatic subarachnoid haemorrhage who returned to baseline and was discharged home only to return within 2 weeks with diffuse subarachnoid and intraventricular re-haemorrhage. A dissecting aneurysm of a duplicated (fenestrated) V4 vertebral artery segment was identified as a rare cause of rebleeding. We describe a course complicated by severe vasospasm delaying aneurysm detection and treatment. Dissecting aneurysms in children should be considered in all cases of delayed post-traumatic cranial rebleeding, particularly where there is anomalous arterial anatomy.

Surgical revascularizations for pediatric moyamoya: a systematic review, meta-analysis, and meta-regression analysis.

INTRODUCTION: There is no clear consensus regarding the technique of surgical revascularization for moyamoya disease and syndrome (MMD/MMS) in the pediatric population. Previous meta-analyses have attempted to address this gap in literature but with methodological limitations that affect the reliability of their pooled estimates. This meta-analysis aimed to report an accurate and transparent comparison between studies of indirect (IB), direct (DB), and combined bypasses (CB) in pediatric patients with MMD/MMS. METHODS: In accordance with PRISMA guidelines, systematic searches of Medline, Embase, and Cochrane Central were undertaken from database inception to 7 October 2022. Perioperative adverse events were the primary outcome measure. Secondary outcomes were rates of long-term revascularization, stroke recurrence, morbidity, and mortality. RESULTS: Thirty-seven studies reporting 2460 patients and 4432 hemispheres were included in the meta-analysis. The overall pooled mean age was 8.6 years (95% CI: 7.7; 9.5), and 45.0% were male. Pooled proportions of perioperative adverse events were similar between the DB/CB and IB groups except for wound complication which was higher in the former group (RR = 2.54 (95% CI: 1.82; 3.55)). Proportions of post-surgical Matsushima Grade A/B revascularization favored DB/CB over IB (RR = 1.12 (95% CI 1.02; 1.24)). There was no significant difference in stroke recurrence, morbidity, and mortality. After meta-regression analysis, year of publication and age were significant predictors of outcomes. CONCLUSIONS: IB, DB/CB are relatively effective and safe revascularization options for pediatric MMD/MMS. Low-quality GRADE evidence suggests that DB/CB was associated with better long-term angiographic revascularization outcomes when compared with IB, although this did not translate to long-term stroke and mortality benefits.

Comparison of endoscopic sinus sampling versus intracranial sampling for microbiological diagnosis of intracranial infection in children: a case series and literature review.

INTRODUCTION: Intracranial infection is often associated with contiguous sinus infection, with Streptococcus intermedius being the most common pathogen. Microbiological assessment is possible via sinus or intracranial sampling. While a sinus approach is minimally invasive, it is not clear whether this yields definitive microbiological diagnosis leading to optimized antimicrobial therapy and avoidance of intracranial surgery. METHODS: A retrospective review of a prospectively collected electronic departmental database identified patients between 2019 and 2022. Further demographic and microbiological information was obtained from electronic patient records and laboratory management systems. RESULTS: Thirty-one patients were identified with intracranial subdural and/or epidural empyema and concurrent sinus involvement during the 3-year study period. The median age of onset was 10 years with a slight male predominance (55%). All patients had intracranial sampling with 15 patients undergoing sinus sampling in addition. Only 1 patient (7%) demonstrated identical organism(s) grown from both samples. Streptococcus intermedius was the most common pathogen in intracranial samples. Thirteen patients (42%) had mixed organisms from their intracranial cultures and 57% of samples undergoing bacterial PCR identified additional organisms, predominantly anaerobes. Sinus samples had a significant addition of nasal flora and Staphylococcus aureus which was rarely grown from intracranial samples. Of concern, 7/14 (50%) of sinus samples did not identify the main intracranial pathogen diagnosed on intracranial culture and additional PCR. Literature review identified 21 studies where sinus drainage was used to treat intracranial empyemas, with only 6 authors reporting concurrent microbiology results. This confirmed our cohort to be the largest comparative study in the current literature. No center has observed a greater than 50% concordance in microbiological diagnoses. CONCLUSION: Endoscopic sinus surgery may have therapeutic benefit, but it is not an appropriate approach for microbiological diagnosis in pediatric subdural empyemas. High rates of contaminating nasal flora can lead to misdiagnosis and inappropriate treatment. Routine addition of 16S rRNA PCR to intracranial samples is recommended.

Initial UK series of endoscopic suturectomy with postoperative helmeting for craniosynostosis: early report of perioperative experience.

BACKGROUND: Endoscopic suturectomy with postoperative helmeting (ESCH) has emerged as a successful treatment for craniosynostosis, initially in North America. We report early outcomes from the first cohort of ESCH patients treated in the United Kingdom (UK). METHODS: Retrospective cohort study with electronic chart review. RESULTS: 18 consecutive patients from the first ESCH procedure in UK (May 2017) until January 2020 identified. 12 male and 6 female infantsd, with a mean age of 4.6 months (range 2.5-7.8 months) and weight of 6.8 kg (range 4.8-9.8 kg). Diagnoses were metopic (n = 8), unicoronal (n = 7), sagittal (n = 2) and multi-sutural (n = 1) synostoses. Median incision length was 3 cm (range 2-10 cm). 16/18 received no blood products, with 2 (both metopics) requiring transfusion (1 donor exposure). Mean operative time (including anaesthesia) was 96 min (range 40-127 min). Median length of hospital stay was 1 night. 1 surgical complication (superficial infection). All patients are currently undergoing helmet orthosis therapy. So far, no patients have required revisional or squint surgery. CONCLUSION: Early experience from the first UK cohort of ESCH suggests that this is a safe and well tolerated technique with low morbidity, transfusion and short hospital stay. Long-term results in terms of shape, cosmetic and developmental outcome are awaited.

An algorithmic clinicoradiological approach to paediatric cranial vault lesions: distinguishing normal variants from pathologies.

Lesions of the paediatric cranial vault are diverse both in their presentation and aetiology. As such, they pose a diagnostic challenge to the paediatric neurosurgeon and neuroradiologist. In this article, we delineate the spectrum of paediatric calvarial pathology into four distinct groups: (1) lytic lesion(s); (2) focal sclerotic lesion(s); (3) diffuse cranial vault sclerosis; and (4) abnormal shape of the cranial vault. It is our aim that this more pragmatic, algorithmic approach may mitigate diagnostic uncertainty and aid the more accurate diagnosis of paediatric calvarial lesions.

3-Dimensional Morphometric Outcomes After Endoscopic Strip Craniectomy for Unicoronal Synostosis.

BACKGROUND: Endoscopic strip craniectomy with postoperative helmeting (ESCH) for unicoronal synostosis has shown to be a less morbid procedure when compared with fronto-orbital remodeling (FOR). We aim in this pilot study to report objective methods and quantitative morphologic outcomes of endoscopically treated unicoronal synostosis using 3-dimensional surface scans. METHODS: Our electronic records were reviewed for ophthalmological, neurodevelopmental outcomes, and helmet-related complications. For morphologic outcomes, the following parameters were used: Cranial Index, Cranial Vault Asymmetry Index, Anterior Symmetry Ratio (ASR), and Root Mean Square between the normal and synostotic sides of the head. Three-dimensional stereophotogrammetry scans were evaluated at 3 time points preoperative, 6 months post-op, and at the end of the treatment, which was compared with age-matched scans of normal controls and FOR patients. Nonparametric tests were used for statistical analysis. RESULTS: None of the ESCH cases developed strabismus, major neurodevelopmental delay, or helmet complications. All morphologic parameters improved significantly at 6 months post-op except for the Cranial Vault Asymmetry Index. The ASR was the only parameter to change significantly between 6 months post-op and final scans. At end of helmet treatment, ASR and Root Mean Square differed significantly between the ESCH and both FOR and control groups. CONCLUSIONS: Endoscopic strip craniectomy with postoperative helmeting for single unicoronal synostosis had excellent clinical outcomes. Most of the improvement in head morphology occurred in the first 6 months of treatment. Despite the normalization of the overall head shape, there was residual asymmetry in the frontal and temporal regions of the head.

Does the Mutation Type Affect the Response to Cranial Vault Expansion in Children With Apert Syndrome?

LEVEL OF EVIDENCE: III.

Imaging characteristics and neurosurgical outcome in subjects with agenesis of the corpus callosum and interhemispheric cysts.

PURPOSE: To explore the relationships between clinical-radiological features and surgical outcomes in subjects with interhemispheric cysts (IHC) and corpus callosum anomalies. METHODS: We reviewed the clinico-radiological and neurosurgical data of 38 patients surgically treated with endoscopic fenestration, shunting, or combined approaches from 2000 to 2018 (24 males, median age 9 years). Pre- and postoperative changes in IHC volume were calculated. Outcome assessment was based on clinico-radiological data. Group comparisons were performed using χ2, Fisher exact, Mann-Whitney U, and Kruskal-Wallis tests. RESULTS: Median age at first surgery was 4 months (mean follow-up 8.3 years). Eighteen individuals (47.3%) required > 1 intervention due to IHC regrowth and/or shunt malfunction. Larger preoperative IHC volume (P = .008) and younger age at surgery (P = .016) were associated with cyst regrowth. At last follow-up, mean cystic volume was 307.8 cm3, with IHC volume reduction > 66% in 19/38 (50%) subjects. The neurological outcome was good in 14/38 subjects (36.8%), fair in 18/38 (47.3%), and poor in 6/38 (15.7%). There were no differences in the postoperative cyst volume with respect to either the type of first surgery or overall surgery type. Higher absolute postoperative IHC reduction was observed in subjects who underwent both IHC fenestration and shunting procedures (P < .0001). No differences in neurological outcome were found according to patient age at surgery or degree of IHC reduction. CONCLUSION: Endoscopic fenestration and shunting approaches are both effective but often require multiple procedures especially in younger patients. Larger IHC are more frequently complicated by cyst regrowth after surgery.

A rare case of atlantoaxial rotatory fixation after posterior calvarial vault expansion surgery in a Crouzon patient.

INTRODUCTION: Atlantoaxial rotatory fixation (AARF) is a rare condition that occurs most commonly in children. The torticollis caused by AARF usually presents as abnormal posturing of the head and neck, with rotation of the chin to the opposite side. AARF in children could occur due to congenital bony malformation, minor trauma, upper respiratory tract infections (Grisel's syndrome), postoperatively after head and neck (ENT) surgery, and unknown reasons. AARF in the postoperative patient is a rare and poorly understood entity. METHODS: The authors present a case report of a 2-year-old boy with Crouzon Syndrome undergoing posterior calvarial vault expansion (PVE) surgery that developed AARF as a complication. RESULTS: The authors believe that cranial vault surgery should be considered a potential risk procedure for AARF, especially if it is done in susceptible populations (syndromic craniosynostosis patients) with other underlying sequelae (tonsillar ectopia or syringomyelia). During surgery, careful attention should be paid to maintaining a neutral alignment of the patient's cervical spine as rotatory movements under anaesthesia and muscle relaxation may be contributory factors. CONCLUSION: AARF should be suspected and investigated in children with painful torticollis after craniofacial surgery.

Observations on the growth of temporalis muscle: A 3D CT imaging study.

This study investigates the hypothesis that there is, during childhood, a disproportionate age-related expansion of the origin of temporalis muscle compared to the growth of the underlying skull. Lateral projections of 50 randomly selected 3D reformatted computerized tomographic (CT) scans (yielding 100 temporalis muscles) of children aged >0.6 to 15 years scanned for conditions that did not affect the shape of their head or face were windowed to provide the optimum delineation of temporalis muscle against the underlying bone. Vertical and anterior-posterior measurements of the muscle made independently by two observers were compared with those of the skull along the same planes. The development of the anterior temporal crest was also assessed. The intraclass correlation coefficient for differences in the measurements made by each observer ranged from good to excellent. The muscle and skull measurements were used to produce a ratio of muscle-to-skull lengths in both vertical and horizontal planes. Analysis of these ratios showed a statistically significant increase in the vertical reach of temporalis with age (Pearson correlation coefficient (R) =0.7826; p < 0.05) compared to the growth of the skull along the planes chosen for the study-but less so for its horizontal reach (R = 0.5073. p < .001). There were no significant differences between right/left or male/female measurements. There was also a substantial level of agreement between both observers in their assessment of the development of the temporal crest. The mean age of children in whom a fully formed temporal crest could be identified (10.6 years) was significantly greater (p < 0.001) than that of the 38 remaining subjects (6.0 years). These results confirm that there is, in response to increased masticatory/dietary demands during childhood, a disproportionate increase in the vertical and (to a lesser extent) horizontal reach of temporalis muscle over its origin from the temporal, frontal, sphenoid, and parietal bones compared the growth of the skull. It is proposed that surgical interference with this normal process is responsible for the soft tissue component of late-developing deformity that can occur following early (at 6-18 months of age) operations for the correction of trigonocephalic head shape associated with metopic synostosis.

Management of haemorrhagic stroke secondary to arteriovenous malformations in childhood.

AIMS: The aim of this study is to describe the outcome and management of all children who have presented with haemorrhagic stroke (HS) secondary to an arteriovenous malformation (AVM) at a single UK centre over a 13-year period. METHODS: All children with HS managed at our institution (2005-2018) were identified and those with underlying AVMs were studied. Clinical and imaging data were obtained from medical records. Outcome was scored using the Recovery and Recurrence Questionnaire. RESULTS: Ninety-three children (median age 8.8 years; 56 males; 8 neonates) presented with both global and focal features (28 had Glasgow Coma Score < 8). Haemorrhage was intraparenchymal in 72; prior risk factors present in 14. An underlying vascular lesion was identified in 68/93, most commonly AVM (n = 48). A systemic cause was found in 10, cerebral venous thrombosis in three, and 9 remain unidentified despite neuroradiological investigation. Median follow-up was 2.4 years, six died, and one was lost to follow-up. Outcome was rated as good in 60/86. Of the 48 AVMs, 3 were Spetzler-Martin (SM) grade 1, 21 SM 2, 21 SM3 and 3 SM4. One patient was treated conservatively as the AVM was too high risk to treat. At follow-up, 19 with AVM were angiographically cured, all with low SM grade and with the use of a single modality in 9 cases (all low SM grade). CONCLUSION: Although children with acute HS are extremely unwell at presentation, supportive care results in a good outcome in the majority. Complete obliteration for childhood AVMs is challenging even with low-grade lesions with multimodal treatment.

Ventriculoatrial and ventriculopleural shunts as second-line surgical treatment have equivalent revision, infection, and survival rates in paediatric hydrocephalus.

PURPOSE: Ventriculoatrial (VA) and ventriculopleural (VPL) shunts are used as alternatives when CSF diversion to the peritoneal compartment with a ventriculoperitoneal (VP) shunt is not possible. The objective of this study is to compare directly the shunt survival and complications for both procedures in this setting in children. METHODS: A retrospective analysis of 54 consecutive patients who underwent VA (36) or VPL (18) shunt insertion between January 2002 and December 2017 was conducted. RESULTS: The overall mean follow-up was 4.1 (SD 4.3) years, 2.8 (SD 4.1) for VPL and 4.7 (SD 4.4) for VA shunts, respectively (p = 0.11). Twenty-four (66.7%) patients in the VA group and 9 (50.0%) in the VPL group underwent shunt revision (p = 0.236); mean number of revisions was 2.2 (SD 3.0) and 0.94 (SD 1.4) in the VA and VPL groups (p = 0.079). Median time to failure was 8.5 (IQr 78, range 0-176) months for VA and 5.50 (IQr 36, range 0-60) for VPL shunts (log rank (Mantel-Cox) 0.832). Shunt survival at 3, 6, 12 and 30 months was 60.6, 51.5, 36.4 and 27.3%, respectively, for VA and 56.3, 43.8, 37.5 and 37.5% for VPL shunts (log rank (Mantel-Cox) test value 0.727). The infection rate was 13.8% for VA and 5.6% for VPL shunts (p = 0.358). Four patients with VPL shunts (22.2%) developed pleural effusions. Fourteen deaths (25.9%) were recorded during follow-up, 8 (22.2%) in the VA and 6 (33.3%) in the VPL group (p = 0.380); two of the deaths in the VA group were shunt-related. CONCLUSION: This study demonstrates that the outcomes of VA and VPL shunts, when used as second-line surgical treatment in paediatric hydrocephalus, were similar, as were the revision, infection and survival rates. The shorter longevity of these shunts compared with the general shunted population may reflect the complex nature of these children.

Post-haemorrhagic hydrocephalus is associated with poorer surgical and neurodevelopmental sequelae than other causes of infant hydrocephalus.

PURPOSE: This retrospective cohort study aimed to investigate the surgical and neurodevelopmental outcomes (NDO) of infant hydrocephalus. We also sought to determine whether these outcomes are disproportionately poorer in post-haemorrhagic hydrocephalus (PHH) compared to other causes of infant hydrocephalus. METHODS: A review of all infants with hydrocephalus who had ventriculoperitoneal (VP) shunts inserted at Great Ormond Street Hospital (GOSH) from 2008 to 2018 was performed. Demographic, surgical, neurodevelopmental, and other clinical data extracted from electronic patient notes were analysed by aetiology. Shunt survival, NDO, cerebral palsy (CP), epilepsy, speech delay, education, behavioural disorders, endocrine dysfunction, and mortality were evaluated. RESULTS: A total of 323 infants with median gestational age of 37.0 (23.29-42.14) weeks and birthweight of 2640 g (525-4684 g) were evaluated. PHH was the most common aetiology (31.9%) and was associated with significantly higher 5-year shunt revision rates, revisions beyond a year, and median number of revisions than congenital or "other" hydrocephalus (all p < 0.02). Cox regression demonstrated poorest shunt survival in PHH, related to gestational age at birth and corrected age at shunt insertion. PHH also had the highest rate of severe disabilities, increasing with age to 65.0% at 10 years, as well as the highest CP rate; only genetic hydrocephalus had significantly higher endocrine dysfunction (p = 0.01) and mortality rates (p = 0.04). CONCLUSIONS: Infants with PHH have poorer surgical and NDO compared to all other aetiologies, except genetic hydrocephalus. Research into measures of reducing neurodisability following PHH is urgently required. Long-term follow-up is essential to optimise support and outcomes.

Sporting activity after craniosynostosis surgery in children: a source of parental anxiety.

PURPOSE: Craniosynostosis correction involves major skull surgery in infancy-a potential source of worry for parents when their treated children begin involvement in sports. METHODS: Electronic multiple choice survey of parents of children who had undergone craniosynostosis surgery in infancy using 5-point Likert scales. RESULTS: Fifty-nine completed surveys were obtained from parents of children who had undergone previous craniosynostosis surgery. Mean age of children was 7.8 years (range 3 months to 22 years), with 36 non-syndromic and 23 syndromic cases. The most common surgery was fronto-orbital remodelling (18). Fifty-two of 59 were involved in athletic activity. The most intense sport type was non-contact in 23, light contact in 20, heavy contact in 4 and combat in 5. Participation level was school mandatory in 12, school club in 17, non-school sport club in 21 and regional representative in 2. One child had been advised to avoid sport by an external physician. Mean anxiety (1-5 Likert) increased with sport intensity: non-contact 1.7, light contact 2.2, heavy contact 3.5 and combat 3.6. Twenty-nine of 59 parents had been given specific advice by the Craniofacial Team regarding athletic activity, 28 of which found useful. Three sport-related head injuries were reported, none of which required hospitalisation. CONCLUSION: Little information exists regarding sports for children after craniosynostosis surgery. This study suggests that parental anxiety remains high, particularly for high impact/combat sports, and that parents would like more information from clinicians about the safety of post-operative sporting activities.

Spring-assisted posterior vault expansion-a single-centre experience of 200 cases.

PURPOSE: Children affected by premature fusion of the cranial sutures due to craniosynostosis can present with raised intracranial pressure and (turri)brachycephalic head shapes that require surgical treatment. Spring-assisted posterior vault expansion (SA-PVE) is the surgical technique of choice at Great Ormond Street Hospital for Children (GOSH), London, UK. This study aims to report the SA-PVE clinical experience of GOSH to date. METHODS: A retrospective review was carried out including all SA-PVE cases performed at GOSH between 2008 and 2020. Demographic and clinical data were recorded including genetic diagnosis, craniofacial surgical history, surgical indication and assessment, age at time of surgery (spring insertion and removal), operative time, in-patient stay, blood transfusion requirements, additional/secondary (cranio)facial procedures, and complications. RESULTS: Between 2008 and 2020, 200 SA-PVEs were undertaken in 184 patients (61% male). The study population consisted of patients affected by syndromic (65%) and non-syndromic disorders. Concerns regarding raised intracranial pressure were the surgical driver in 75% of the cases, with the remainder operated for shape correction. Median age for SA-PVE was 19 months (range, 2-131). Average operative time for first SA-PVE was 150 min and 87 for spring removal. Median in-patient stay was 3 nights, and 88 patients received a mean of 204.4 ml of blood transfusion at time of spring insertion. A single SA-PVE sufficed in 156 patients (85%) to date (26 springs still in situ at time of this analysis); 16 patients underwent repeat SA-PVE, whilst 12 underwent rigid redo. A second SA-PVE was needed in significantly more cases when the first SA-PVE was performed before age 1 year. Complications occurred in 26 patients with a total of 32 events, including one death. Forty-one patients underwent fronto-orbital remodelling at spring removal and 22 required additional cranio(maxillo)facial procedures. CONCLUSIONS: Spring-assisted posterior vault expansion is a safe, efficient, and effective procedure based on our 12-year experience. Those that are treated early in life might require a repeat SA-PVE. Long-term follow-up is recommended as some would require additional craniomaxillofacial correction later in life.

Fat infiltration in the multifidus muscle is related to inflammatory cytokine expression in the muscle and epidural adipose tissue in individuals undergoing surgery for intervertebral disc herniation.

PURPOSE: Recent animal studies have discovered dysregulation of local inflammatory activity as a novel mechanism to explain fat and connective tissue accumulation in the multifidus muscle in association with intervertebral disc (IVD) degeneration/injury. This study aimed to test whether similar mechanisms are active in humans by investigation of whether expression of inflammatory genes in the multifidus muscle differed between individuals with low and high levels of intra-muscular fat in the muscle. The secondary aims were to compare inflammatory gene expression in the intra-muscular, subcutaneous and epidural fat between groups. METHODS: Muscle and fat were procured from 24 individuals undergoing spine surgery for IVD herniation. Gene expression was quantified using qPCR assays. Participants were allocated to high- and low-fat infiltration groups based on clinical assessment of multifidus fat using Kjaer grading of MRI. RESULTS: TNF expression in the multifidus muscle was greater in participants with high rather than low levels of fat infiltration. This group also had greater expression of leptin, but lower arginase-1 (marker of anti-inflammatory M2 macrophages) in intra-muscular and subcutaneous adipose tissue, and greater expression of TNF, adiponectin and nitric oxide synthase 2 (marker of pro-inflammatory M1 macrophages) in epidural fat. CONCLUSION: The results support the hypothesis that IVD degeneration is associated with dysregulation of the inflammatory state of the local multifidus muscle, which provides initial evidence for translation of some, but not all, observations from recent animal studies to humans. Discovery of inflammatory dysregulation in epidural adipose tissue has potential for broad impact on tissue health and LBP symptoms.

Local Soft Tissue and Bone Displacements Following Midfacial Bipartition Distraction in Apert Syndrome - Quantification Using a Semi-Automated Method.

ABSTRACT: Patients with Apert syndrome experience midfacial hypoplasia, hypertelorism, and downslanting palpebral fissures which can be corrected by midfacial bipartition distraction with rigid external distraction device. Quantitative studies typically focus on quantifying rigid advancement and rotation postdistraction, but intrinsic shape changes of bone and soft tissue remain unknown. This study presents a method to quantify these changes. Pre- and post-operative computed tomography scans from patients with Apert syndrome undergoing midfacial bipartition distraction with rigid external distraction device were collected. Digital Imaging and Communications in Medicine files were converted to three-dimensional bone and soft tissue reconstructions. Postoperative reconstructions were aligned on the preoperative maxilla, followed by nonrigid iterative closest point transformation to determine local shape changes. Anatomical point-to-point displacements were calculated and visualized using a heatmap and arrow map. Nine patients were included.Zygomatic arches and frontal bone demonstrated the largest changes. Mid-lateral to supra-orbital rim showed an upward, inward motion. Mean bone displacements ranged from 3.3 to 12.8 mm. Soft tissue displacements were relatively smaller, with greatest changes at the lateral canthi. Midfacial bipartition distraction with rigid external distraction device results in upward, inward rotation of the orbits, upward rotation of the zygomatic arch, and relative posterior motion of the frontal bone. Local movements were successfully quantified using a novel method, which can be applied to other surgical techniques/syndromes.