A regulatory variant impacting TBX1 expression contributes to basicranial morphology in Homo sapiens.

Changes in gene regulatory elements play critical roles in human phenotypic divergence. However, identifying the base-pair changes responsible for the distinctive morphology of Homo sapiens remains challenging. Here, we report a noncoding single-nucleotide polymorphism (SNP), rs41298798, as a potential causal variant contributing to the morphology of the skull base and vertebral structures found in Homo sapiens. Screening for differentially regulated genes between Homo sapiens and extinct relatives revealed 13 candidate genes associated with basicranial development, with TBX1, implicated in DiGeorge syndrome, playing a pivotal role. Epigenetic markers and in silico analyses prioritized rs41298798 within a TBX1 intron for functional validation. CRISPR editing revealed that the 41-base-pair region surrounding rs41298798 modulates gene expression at 22q11.21. The derived allele of rs41298798 acts as an allele-specific enhancer mediated by E2F1, resulting in increased TBX1 expression levels compared to the ancestral allele. Tbx1-knockout mice exhibited skull base and vertebral abnormalities similar to those seen in DiGeorge syndrome. Phenotypic differences associated with TBX1 deficiency are observed between Homo sapiens and Neanderthals (Homo neanderthalensis). In conclusion, the regulatory divergence of TBX1 contributes to the formation of skull base and vertebral structures found in Homo sapiens.

Bridging veins at the craniocervical junction: from anatomy to clinical significance in dural arteriovenous shunts.

PURPOSE: Bridging veins (BVs) serve as a route of pial venous reflux, and its anatomy is essential to understand the pathophysiology of dural arteriovenous shunts (dAVSs) around the craniocervical junction (CCJ) (from the jugular foramen level to the atlantal level). However, the anatomical variations of the BVs and their proximal connections remained poorly elucidated. This study aimed to radiologically investigate the anatomy of the bridging veins around CCJ and discuss the clinical significance of these BVs in the dAVS. METHODS: We investigated normal venous anatomy of the BVs from the jugular foramen level to the atlantal level using preoperative computed tomography digital subtraction venography in patients undergoing elective neurosurgery. BVs affected by the dAVSs in the same region were also evaluated. The three types of dAVS, craniocervical junction, anterior condylar, and proximal sigmoid sinus, were investigated. RESULTS: We identified six BV groups: superolateral, anterolateral, lateral, posterior, inferolateral, and inferoposterior. The superolateral and inferolateral groups, connected with the proximal sigmoid sinus and suboccipital cavernous sinus, respectively, were the largest groups. Each group has a specific downstream venous connection. The association with dVASs was observed only in the inferolateral group, which was typically the sole venous drainage in most dAVSs at the CCJ. CONCLUSION: We reported detailed anatomy of BVs from the jugular level to the atlantal level, which enhanced our understanding of the pathophysiology of dAVSs in the corresponding region.

Classification, angioarchitecture and treatment outcomes of medullary bridging vein-draining dural arteriovenous fistulas in the foramen magnum region: a multicenter study.

PURPOSE: This study aimed to classify medullary bridging vein-draining dural arteriovenous fistulas (MBV-DAVFs) located around the foramen magnum (FM) according to their location and characterize their angioarchitecture and treatment outcomes. METHODS: Patients with MBV-DAVFs diagnosed between January 2013 and October 2022 were included. MBV-DAVFs were classified into four groups. Jugular vein-bridging vein (JV-BV) DAVF: located in proximity to jugular fossa, Anterior condylar vein (ACV)-BV DAVF: proximity to anterior condylar canal, Marginal sinus (MS)-BV DAVF: lateral surface of FM and Suboccipital cavernous sinus (SCS)-BV DAVF: proximity to dural penetration of vertebral artery. RESULTS: Twenty patients were included, three JV-BV, four ACV-BV, three MS-BV and ten SCS-BV DAVFs, respectively. All groups showed male predominance. There were significant differences in main feeders between JV (jugular branch of ascending pharyngeal artery) and SCS group (C1 dural branch). Pial feeders from anterior spinal artery (ASA) or lateral spinal artery (LSA) were visualized in four SCS and one MS group. Drainage pattern did not differ between groups. Transarterial embolization (TAE) was performed in three, two, one and two cases and complete obliteration was obtained in 100%, 50%, 100% and 0% in JV, ACS, MS and SCS group, respectively. Successful interventions without major complications were finally obtained in 100%, 75%, 100%, and 40% in JV, ACS, MS and SCS group, respectively. CONCLUSION: JV-BV DAVFs were successfully treated using TAE alone. SCS-BV DAVFs were mainly fed by small C1 dural branches of vertebral artery often with pial feeders from ASA or LSA, and difficultly treated by TAE alone.

Promising horizons in achondroplasia along with the development of new drugs.

Achondroplasia (ACH) is a representative skeletal disorder characterized by rhizomelic shortened limbs and short stature. ACH is classified as belonging to the fibroblast growth factor receptor 3 (FGFR3) group. The downstream signal transduction of FGFR3 consists of STAT1 and RAS/RAF/MEK/ERK pathways. The mutant FGFR3 found in ACH is continuously phosphorylated and activates downstream signals, resulting in abnormal proliferation and differentiation of chondrocytes in the growth plate and cranial base synchondrosis. A patient registry has been developed and has contributed to revealing the natural history of ACH patients. Concerning the short stature, the adult height of ACH patients ranges between 126.7-135.2 cm for men and 119.9-125.5 cm for women in many countries. Along with severe short stature, foramen magnum stenosis and spinal canal stenosis are major complications: the former leads to sleep apnea, breathing disorders, myelopathy, hydrocephalus, and sudden death, and the latter causes pain in the extremities, numbness, muscle weakness, movement disorders, intermittent claudication, and bladder-rectal disorders. Growth hormone treatment is available for ACH only in Japan. However, the effect of the treatment on adult height is not satisfactory. Recently, the neutral endopeptidase-resistant CNP analogue vosoritide has been approved as a new drug for ACH. Additionally in development are a tyrosine kinase inhibitor, a soluble FGFR3, an antibody against FGFR3, meclizine, and the FGF2-aptamer. New drugs will bring a brighter future for patients with ACH.

Alteration of major venous drainage routes in a patient with achondroplasia after ventriculoperitoneal shunt placement.

Achondroplasia is the most common form of dwarfism, caused by a mutation in fibroblast growth factor receptor 3 gene, leading to multiple pathological conditions. Herein, we present a case of an infant with achondroplasia associated with hydrocephalus and severe foramen magnum stenosis. Computed tomography (CT) venography showed prominent suboccipital emissary veins comprising major venous drainage routes and hypoplastic transverse sinuses, which increased the risk of foramen magnum decompression. The infant was initially treated with ventriculo-peritoneal (VP) shunt. After 8 months, CT venography showed regression of suboccipital emissary veins and more prominent transverse sinuses. Subsequently, foramen magnum decompression was safely performed without sacrificing major venous drainage routes.

Retroflexed dens in paediatric Chiari 1 patients and implications: Single centre retrospective study.

INTRODUCTION: Chiari 1 malformation and hind brain hernia can be associated with skull base and craniocervical anomalies. One of the more recently associated anomalies is a retroverted or retroflexed odontoid process or dens. We conducted a retrospective study of our operated symptomatic and conservatively managed asymptomatic Chiari cohort to assess the impact of dens retroflexion on rate of revision or cerebrospinal fluid diversion following primary foramen magnum decompression (FMD). METHODS: We undertook a retrospective study of all foramen magnum decompression (FMD) cases for Chiari type 1 malformation performed over a 15-year period in a single tertiary paediatric neurosurgical unit. For comparison, non-operated asymptomatic Chiari cases were considered as reference cohort. Information gathered included: demographics, age, sex, length of cerebellar tonsils below McRae's line, pB-C2 distance (a line drawn perpendicular to one drawn between the basion and the posterior aspect of the C2 body), angle of retroflexion (angle formed between a line drawn through the odontoid synchondrosis and its intersection with a line drawn from the tip of the odontoid process) and angle of retroversion (angle formed between the line drawn from the base of C2 and its intersection with a line drawn from the tip of the odontoid process). Grade of retroflexion was measured using pre-operative mid-sagittal MR images and classified as grade 0 (> 90°), grade 1 (85°-89°); grade 2 (80°-84°) and grade 3 (< 80°). The rates for redo surgery or need for cerebrospinal fluid (CSF) diversion were obtained from clinical records and compared in the operated and non-operated groups. RESULTS: One hundred twenty-six Chiari 1 patients were included in this study with adequate imaging. Sixty-five patients were in the non-operated asymptomatic cohort with 61 patients in the operated symptomatic cohort. Mean age of non-operated cohort was 10.2 years with M:F ratio (30:35). Mean cerebellar tonsillar length below McRae's line was 10.3 mm. 7.7% of this cohort had associated syrinx. Mean angles of retroversion and retroflexion were 76 and 78°, respectively. Retroflexion grades included (9.2% grade 1, 35% grade 2 and 52.3% grade 3). pB-C2 distance was 6.8 mm. Mean age of operated cohort was 11.3 years, with M:F ratio (21:40). Mean cerebellar tonsillar length below McRae's line was 15 mm. 45.9% of this cohort had associated syrinx. Mean angles of retroversion and retroflexion were 73 and 74.5°, respectively. Retroflexion grades included (4.9% grade 1, 16.5% grade 2 and 78.6% grade 3). pB-C2 distance was 6.9 mm. No association was identified between retroflexion grade and rate of revision or CSF diversion following primary foramen magnum decompression. CONCLUSION: The operated Chiari 1 cohort had more retroflexed dens, longer tonsils and associated syrinx compared to the non-operated asymptomatic cohort.

Novel classification of foramen magnum meningiomas predicted by topographic position relative to neurovascular bundle.

PURPOSE: Proximity to critical neurovascular structures can create significant obstacles during surgical resection of foramen magnum meningiomas (FMMs) to the detriment of treatment outcomes. We propose a new classification that defines the tumor's relationship to neurovascular structures and assess correlation with postoperative outcomes. METHODS: In this retrospective review, 41 consecutive patients underwent primary resection of FMMs through a far lateral approach. Groups defined based on tumor-neurovascular bundle configuration included Type 1, bundle ventral to tumor; Type 2a-c, bundle superior, inferior, or splayed, respectively; Type 3, bundle dorsal; and Type 4, nerves and/or vertebral artery encased by tumor. RESULTS: The 41 patients (range 29-81 years old) had maximal tumor diameter averaging 30.1 mm (range 12.7-56 mm). Preoperatively, 17 (41%) patients had cranial nerve (CN) dysfunction, 12 (29%) had motor weakness and/or myelopathy, and 9 (22%) had sensory deficits. Tumor type was relevant to surgical outcomes: specifically, Type 4 demonstrated lower rates of gross total resection (65%) and worse immediate postoperative CN outcomes. Long-term findings showed Types 2, 3, and 4 demonstrated higher rates of permanent cranial neuropathy. Although patients with Type 4 tumors had overall higher ICU and hospital length of stay, there was no difference in tumor configuration and rates of postoperative complications or 30-day readmission. CONCLUSION: The four main types of FMMs in this proposed classification reflected a gradual increase in surgical difficulty and worse outcomes. Further studies are warranted in larger cohorts to confirm its reliability in predicting postoperative outcomes and possibly directing management decisions.

Preoperative estimation of intracranial compliance in symptomatic children with Chiari malformation type 1: impact on outcome and risk of complications.

BACKGROUND: The role of reduced intracranial compliance (ICC) in the outcome after foramen magnum decompression (FMD) was demonstrated in adults with Chiari malformation Type 1 (CMI). However, similar observations from children treated for CMI are missing. METHODS: We reviewed pediatric cases of CMI referred to FMD between 2006 and 2022. Children with clinical and/or radiological signs suggesting reduced ICC (Group A) underwent overnight measurements of the pulsatile intracranial pressure (ICP): mean ICP wave amplitude (MWA) served as a surrogate marker of ICC. Children with more typical symptoms of CMI (Group B) underwent FMD without preoperative ICC estimation. This study presents the clinical, radiological, and outcome differences between these groups. RESULTS: Sixty-four children (mean age 11.1 ± 4.3 years) underwent FMD: In Group A (n = 30), the finding of reduced ICC as estimated from preoperative ICP measurement resulted in CSF diversion (ventriculoperitoneal shunt) before FMD in 11 children. Two patients required shunt due to complications after FMD (total shunt rate 43%). In Group B (n = 34) treated with FMD without preoperative ICC estimation, five children (15%) required shunting due to complications. In Group A, we found a significantly higher frequency of headache, nausea, fatigue, and dizziness. The outcome assessed by the modified Chicago Chiari Outcome Scale (mean follow-up 83 ± 57 months) was comparable between the groups, but the complication rate after FMD was significantly lower in Group A (7% vs. 32%; p = 0.011). The number of procedures (ICP measurement, FMD, shunt, re-do FMD, shunt revisions) was significantly higher in Group A (2.6 ± 0.9 vs. 1.5 ± 1.1 per patient; p < 0.001). CONCLUSION: In symptomatic children with CMI, the preoperative estimation of ICC from the overnight measurement of pulsatile ICP was more reliable for identifying those with reduced ICC than clinical and radiological assessment alone. When children with abnormally reduced ICC were identified and treated with CSF diversion before FMD, the complication rate was significantly reduced.

How I do it: safe resection of a complex type 3 foramen magnum meningioma with dorsal displacement of the neurovascular bundle.

BACKGROUND: We describe techniques for safe resection of a Type 3 foramen magnum meningioma with dorsal displacement of the accessory nerve rootlets and vertebral artery which limits ventral access to the tumor. METHOD: Partial sectioning of the accessory nerve rootlets may help create larger working space. Topical lidocaine placement on the rootlets of the spinal accessory nerve may mitigate trapezius muscle contraction and facilitates further progress throughout tumor resection. CONCLUSION: Creating safe working corridors between the lower cranial nerves through mobilization or partial sectioning of rootlets in the case of CN XI facilitates tumor resection through a far lateral approach.

Calcifying pseudoneoplasms of the neuraxis (CAPNON) in foramen magnum (cervicomedullary junction) region: a case report and review of the literature.

BACKGROUND AND IMPORTANCE: Calcifying pseudoneoplasms of the neuraxis (CAPNON) is an extremely rare tumor, with nearly 150 cases have been reported in the literature. We present a case of CAPNON at foramen magnum (cervicomedullary junction). We also discuss the histological and radiological features of this rare pathology. CLINICAL PRESENTATION: A 35-year-old male patient presented to our center complaining of neck pain for the last 6 months and for the last 3 months has had headaches associated with nausea, blurred vision and papilledema. The patient's magnetic resonance imaging showed the presence of right craniocervical junction intra-dural extramedullary tumor. Neuro examination showed no neurological deficits. He underwent midline suboccipital craniotomy with C1 laminectomy. The mass was completely resected, and histopathology confirmed it to be a CAPNON. CONCLUSION: We presented a new case of CAPNON at cervicomedullary junction. The tumor was radically resected, without any complications. Resection of this kind of tumor is curative, and the need for post-operative chemo or radiotherapy is unnecessary, which depends on the outcome of future research and the long-term follow ups.

Transverse and oblique course of the vertebral artery over the medullospinal junction.

PURPOSE: The vertebral artery (VA) pierces the dura mater and continues with the intradural V4 segment. Once entered into the dura mater, the VA ascends from the infero-lateral to the antero-superior side of the medulla. Scarce reports of VAs compressing the medullospinal junction (MSJ) are available. We therefore aimed to determine the incidence of a course of the AV over the MSJ. METHOD: One hundred sixty-two archived CT angiogram files were documented in the study. We recorded the cases in which the VA crossed the MSJ. We assessed the VA as dominant, non-dominant or co-dominant. RESULTS: In 32 cases (19.75%), we identified intradural AVs on the ventral side of the MSJs. The incidence of this course of the VA was 17.1% in males and 23.81% in females. Of the 32 cases, the VA was non-dominant in 6, dominant in 14, and co-dominant in 12. CONCLUSION: The VA course over the MSJ is not rare. Therefore, when specific neurological signs of MSJ or medulla compression are found, the course of the VA should be documented on CT or MRI angiograms.

Comprehensive comparative study of Chiari-like malformation in veterinary and human medicine.

This review aims to enrich our understanding of Chiari-like malformation (CLM) by combining human and veterinary insights, and providing a detailed cross-species overview. CLM is a developmental abnormality characterised by caudal displacement of the hindbrain into the foramen magnum due to an entire brain parenchymal shift caused by insufficient skull volume. This malformation leads to a progressive obstruction at the craniocervical junction, which disrupts the normal cerebrospinal fluid flow, leading to secondary syringomyelia. The clinical signs of CLM and syringomyelia include phantom scratching, head tilt, head tremor, ataxia, tetraparesis, pain, muscle atrophy, and scoliosis or torticollis. Magnetic resonance imaging remains the gold standard for diagnosing CLM, since it allows the visualisation of abnormal findings such as the caudal cerebellar herniation, caudal cerebellar compression from occipital dysplasia, and attenuated cerebrospinal fluid cisternae. Although various medical and surgical interventions, including foramen magnum decompression, can provide temporary symptomatic/clinical sign relief, current literature shows a lack of sustained long-term efficacy. Therefore, additional research is needed to evaluate the long-term effects of existing treatment strategies and to compare different techniques utilised in conjunction with foramen magnum decompression.

A Prevalence Anatomic-Imaging Study of the Posterior Inferior Cerebellar Artery's Origin.

Background and Objectives: Typically, the vertebral arteries (VAs) enter the posterior fossa through dural rings and further unite, forming the basilar artery. The posterior inferior cerebellar artery (PICA) is usually a branch of the V4 segment of the VA (intradural origin). It may also leave the V3 suboccipital segment of the VA (extradural origin). The transdural origin of the PICA within the VA's dural ring has been consistently overlooked. A study was designed to determine the topographical patterns of the PICA's origin. Materials and Methods: Determinations were performed in a retrospective sample of 225 computed tomography angiograms. Four types of PICA origin were documented: type 0, absent PICA; type 1, the extradural origin of the PICA from the V3 segment of the VA; type 2, the transdural origin of the PICA within the dural ring; and type 3, the intradural origin of the PICA from the V4 segment of the VA. The bilateral symmetry of types was also investigated. Results: Out of 450 VAs, type 0 (absent PICA) was found in 36%, type 1 (extradural) in 0.44%, type 2 (transdural) in 5.56%, and typical type 3 in just 58%. In types 1 and 2, the PICA entered the posterior fossa through the dural ring and the marginal sinus. In the overall group (N = 225), the type combinations 1_1, 1_2 and 1_3 were not found. Bilaterally absent PICAs occurred in 18.67%. The bilateral combinations 0_1/0_2/0_3/2_2/2_3/3_3 were found, respectively, in 0.89%/3.11%/30.67%/1.78%/4.44%/40.44%. Four of the seventy-eight PICAs opposite to an absent one, three intradural and one transdural, were true bihemispheric PICAs. Conclusions: The PICAs with extradural or transdural origins are facultative contents of the dural ring and are at risk during neurosurgical approaches in the foramen magnum. Rare bihemispheric PICAs could originate either intradurally or within the dural ring.

Accuracy of sex estimation by morphometric evaluation of foramen magnum using computed tomography - a systematic review and meta-analysis.

The objective of this study is to determine whether the morphometric evaluation of the foramen magnum using computed tomography can be used as an accurate tool in estimating the sex of an individual. An extensive search of the databases, PubMed, ProQuest, Google Scholar, and Scopus, was carried out to procure articles that fulfilled the inclusion criteria. The AQUA tool was used to assess the quality of the included studies. A random effects model was used for the meta-analysis of the eligible studies using the STATA software, version 16, 2019 at 95% CI and p ≤ 0.05. Eleven eligible articles that measured the transverse and sagittal diameters of the foramen magnum using computed tomography were included in this study. The sagittal diameter of the foramen magnum was greater than the transverse diameter, and both the diameters were greater in males than in females. Meta-analysis revealed that both transverse and sagittal diameters were more reliable for male sex estimation. Since there is a dimensional variation between the male and female foramen magnum, it can be used for initial sex identification and also as an auxiliary to other advanced methods of sex estimation.

[Accessory nerve meningioma. A case report and literature review]. / Meningioma obolochek dobavochnogo nerva. Klinicheskii sluchai i obzor literatury.

Meningiomas arising from accessory nerve sheath without dural attachment are rare. To date, only 5 cases are described in the literature. A 53-year-old male presented with long history of occipital pain and headaches. Magnetic resonance imaging revealed a small intradural extramedullary contrast enhanced tumor at the level of foramen magnum. The patient underwent microsurgical resection through minimally invasive midline suboccipital approach. According to intraoperative findings, cystic tumor arose from the left accessory nerve without dural attachment. Gross total resection was achieved without damage to the nerve. Histological analysis revealed angiomatous meningioma. Postoperative period was uneventful without new neurological symptoms. Meningiomas can rarely arise from accessory nerve sheath and mimic schwannoma. These tumors may be totally resected without damage to accessory nerve using minimally invasive surgical approaches.

Chiari Malformation Type 1 in Adults.

The term Chiari malformation refers to a heterogeneous group of anatomical abnormalities at the craniovertebral junction. Chiari malformation type 1 (CM1) refers to the abnormal protrusion of cerebellar tonsils through the foramen magnum and is by far the commonest type. Its prevalence is estimated approximately 1%; it is more common in women and is associated with syringomyelia in 25-70% of cases. The prevalent pathophysiological theory proposes a morphological mismatch between a small posterior cranial fossa and a normally developed hindbrain that results in ectopia of the tonsils.In most people, CM1 is asymptomatic and diagnosed incidentally. In symptomatic cases, headache is the cardinal symptom. The typical headache is induced by Valsalva-like maneuvers. Many of the other symptoms are nonspecific, and in the absence of syringomyelia, the natural history is benign. Syringomyelia manifests with spinal cord dysfunction of varying severity. The approach to patients with CM1 should be multidisciplinary, and the first step in the management is phenotyping the symptoms, because they may be due to other pathologies, like a primary headache syndrome. Magnetic resonance imaging, which shows cerebellar tonsillar decent 5 mm or more below the foramen magnum, is the gold standard investigative modality. The diagnostic workup may include dynamic imaging of the craniocervical junction and intracranial pressure monitoring.The management of CM1 is variable and sometimes controversial. Surgery is usually reserved for patients with disabling headaches or neurological deficits from the syrinx. Surgical decompression of the craniocervical junction is the most widely used procedure. Several surgical techniques have been proposed, but there is no consensus on the best treatment strategy, mainly due to lack of high-quality evidence. The management of the condition during pregnancy, restriction to lifestyle related to athletic activities, and the coexistence of hypermobility require special considerations.

Chiari Type 1 Malformation and Syringomyelia in Children: Classification and Treatment Options.

Chiari type 1 malformation (CIM) is defined as tonsillar ectopia of >5 mm, while syringomyelia (SM) is defined as a cerebrospinal fluid (CSF)-filled cavity larger than 3 mm dissecting the spinal cord. Over the last decades, our understanding of these pathologies has grown; however, many controversies still exist almost in every aspect of CIM and SM, including etiology, indication for treatment, timing of treatment, surgical technique, follow-up regime, and outcome. This chapter provides a comprehensive overview on different aspects of CIM and SM and on the still existing controversies, based on the evidence presently available. Future directions for clinical research concerning CIM and SM treatment and outcome are elaborated and discussed as well.

A new supportive approach in the diagnosis of Chiari malformation type 1 in pediatric patients.

PURPOSE: Chiari malformation type 1 (CM-1) is a posterior fossa anomaly characterized by herniation of the cerebellar tonsils from the foramen magnum (FM). This study compares FM, medulla spinalis (MS), and herniated cerebellar tonsils ratios by making area measurements from axial plane MRI in CM-1 patients and the control group. METHODS: Our study evaluated 30 pediatric patients with CM-1 and 30 people in the control group. The lengths of the McRae line, twining line, and clivus line were measured on the posterior cranial fossa evaluation. The areas of FM (AFM), MS (AMS), and herniated cerebellar tonsils (ATONSILS) were measured by axial images. RESULTS: As a result of area measurements obtained from axial cross-sectional MRI, a statistically significant difference was found between CM-1 patients and the control group. According to the results of the ROC analysis, if an individual's AMS/AFM value is above 17.9% or the ATONSILS/AFM value is above 18.4%, it can be interpreted as a CM-1 patient. CONCLUSION: It will be easier to diagnose the patient with the new approach we obtained from axial MR images in addition to sagittal MR images. This method can be a guide in some cases when the surgeons are undecided.

Re-imagining early cloverleaf skull deformity management from front to back approach-30 years on.

The cloverleaf skull deformity remains among the most complicated craniofacial conditions to successfully manage. Many cases achieve largely unsatisfactory outcomes due to the requirement for frequent reoperation on the cranial vault and failure to deal with all the elements of the craniofaciostenosis in a timely fashion. Early cranial vault surgery without addressing the cranial base deformity and its attendant cerebrospinal fluid flow changes is invariably challenging and disappointing. A recent focus on the expansion of the posterior cranial vault as a primary procedure with the greater volume change allows a delay in fronto-orbital advancement and reduced need for repeat surgery. We herein describe three cases of complex multisuture craniosynostosis with cloverleaf skull deformity who underwent neonatal posterior cranial vault decompression along with foramen magnum decompression. Our report examines the safety and rationale for this pre-emptive surgical approach to simultaneously deal with the cranial vault and craniocervical junction abnormalities and thus change the early trajectory of these complex cases.

Unravelling the pathogenesis of foramen magnum stenosis in patients with severe achondroplasia: a CT-based comparison with age-matched controls and FGFR3 craniosynostosis syndromes.

OBJECTIVE: Foramen magnum(FM) stenosis can be responsible for acute and chronic damage to the cervicomedullary junction in children with achondroplasia. The bony anatomy and patterns of suture fusion of the FM in this context are incompletely understood, yet becoming increasingly important in the light of novel medical therapies for achondroplasia. The objective of this study was to describe and quantify bony anatomy and fusion patterns of FM stenosis in patients with achondroplasia using CT scans, comparing them to age-matched controls and other FGFR3 craniosynostosis patients. METHODS: Patients with achondroplasia and severe FM stenosis, classified as achondroplasia foramen magnum score(AFMS) grades 3 and 4, were identified from a departmental operative database. All had pre-operative CT scans of the craniocervical junction. Measurements obtained comprised sagittal diameter (SD), transverse diameter (TD), foramen magnum area, and opisthion thickness. Anterior and posterior interoccipital synchondroses (AIOS and PIOS) were graded by the extent of fusion. These measurements were then compared with CT scans from 3 age-matched groups: the normal control group, children with Muenke syndrome, and children with Crouzon syndrome with acanthosis nigricans (CSAN). RESULTS: CT scans were reviewed in 23 cases of patients with achondroplasia, 23 normal controls, 20 Muenke, and 15 CSAN. Children with achondroplasia had significantly smaller sagittal diameter (mean 16.2 ± 2.4 mm) compared to other groups (control 31.7 ± 2.4 mm, p < 0.0001; Muenke 31.7 ± 3.5 mm, p < 0.0001; and CSAN 23.1 ± 3.4 mm, p < 0.0001) and transverse diameters (mean 14.3 ± 1.8 mm) compared with other groups (control 26.5 ± 3.2 mm, p < 0.0001; Muenke 24.1 ± 2.6 mm, p < 0.0001; CSAN 19.1 ± 2.6 mm, p < 0.0001). This translated into a surface area which was 3.4 times smaller in the achondroplasia group compared with the control group. The median grade of the AIOS fusion achondroplasia group was 3.0 (IQR 3.0-5.0), which was significantly higher compared with the control group (1.0, IQR 1.0-1.0, p < 0.0001), Muenke group (1.0, IQR 1.0-1.0, p < 0.0001), and CSAN (2.0, IQR 1.0-2.0, p < 0.0002). Median PIOS fusion grade was also highest in the achondroplasia group (5.0, IQR 4.0-5.0) compared with control (1.0, IQR 1.0-1.0, p < 0.0001), Muenke (2.5, IQR 1.3-3.0, p < 0.0001), and CSAN (4.0, IQR 4.0-4.0, p = 0.2). Distinct bony opisthion spurs projecting into the foramen magnum were seen in achondroplasia patients but not others, resulting in characteristic crescent and cloverleaf shapes. CONCLUSION: Patients with AFMS stages 3 and 4 have significantly reduced FM diameters, with surface area 3.4 times smaller than age-matched controls. This is associated with premature fusion of the AIOS and PIOS in comparison with controls and other FGFR3-related conditions. The presence of thickened opisthion bony spurs contributes to stenosis in achondroplasia. Understanding and quantifying bony changes at the FM of patients with achondroplasia will be important in the future quantitative evaluation of emerging medical therapies.