Calvarial Expansion Research Articles

Mesenchymal Wnts are required for morphogenetic movements of calvarial osteoblasts during apical expansion.

Apical expansion of calvarial osteoblast progenitors from the cranial mesenchyme (CM) above the eye is integral to calvarial growth and enclosure of the brain. The cellular behaviors and signals underlying the morphogenetic process of calvarial expansion are unknown. Time-lapse light-sheet imaging of mouse embryos revealed calvarial progenitors intercalate in 3D in the CM above the eye, and exhibit protrusive and crawling activity more apically. CM cells express non-canonical Wnt/planar cell polarity (PCP) core components and calvarial osteoblasts are bidirectionally polarized. We found non-canonical ligand Wnt5a-/- mutants have less dynamic cell rearrangements and protrusive activity. Loss of CM-restricted Wntless (CM-Wls), a gene required for secretion of all Wnt ligands, led to diminished apical expansion of Osx+ calvarial osteoblasts in the frontal bone primordia in a non-cell autonomous manner without perturbing proliferation or survival. Calvarial osteoblast polarization, progressive cell elongation and enrichment for actin along the baso-apical axis were dependent on CM-Wnts. Thus, CM-Wnts regulate cellular behaviors during calvarial morphogenesis for efficient apical expansion of calvarial osteoblasts. These findings also offer potential insights into the etiologies of calvarial dysplasias.

Evaluation and Management of Patients with Hydrocephalus in Craniosynostosis.

Hydrocephalus in presence of craniosynostosis, though relatively rare, occurs in 4%-10% cases, with an increased incidence in syndromic craniosynostosis. The optimum management in these patients is unknown. A search was performed on the departmental craniofacial database to identify all patients with craniosynostosis and hydrocephalus from January 2000 to December 2020. Diagnosis was confirmed by a meticulous review of the notes and previous imaging. These patients were grouped into two groups based on the primary treatment they received: either a cerebrospinal fluid (CSF) diversion procedure or a calvarial remodeling procedure. By analyzing the outcomes for each group, we endeavor to rationalize and outline our management strategy for this complex cohort of patients. Sixty-four of 989 patients were confirmed to have hydrocephalus. Of these, 55 patients underwent calvarial expansion while nine had CSF diversion as a primary procedure. Our study demonstrates that the complication rate is lower in the primary calvarial expansion group. Furthermore, the need for a CSF diversion procedure was avoided in a significant number of these patients as a direct result. In the vast majority of patients with craniosynostosis and hydrocephalus, calvarial expansion surgery should be the preferred primary management option.

Cranial Suture Regeneration Mitigates Skull and Neurocognitive Defects in Craniosynostosis

Craniosynostosis results from premature fusion of the cranial suture(s), which contain mesenchymal stem cells (MSCs) that are crucial for calvarial expansion in coordination with brain growth. Infants with craniosynostosis have skull dysmorphology, increased intracranial pressure, and complications such as neurocognitive impairment that compromise quality of life. Animal models recapitulating these phenotypes are lacking, hampering development of urgently needed innovative therapies. Here, we show that Twist1+/- mice with craniosynostosis have increased intracranial pressure and neurocognitive behavioral abnormalities, recapitulating features of human Saethre-Chotzen syndrome. Using a biodegradable material combined with MSCs, we successfully regenerated a functional cranial suture that corrects skull deformity, normalizes intracranial pressure, and rescues neurocognitive behavior deficits. The regenerated suture creates a niche into which endogenous MSCs migrated, sustaining calvarial bone homeostasis and repair. MSC-based cranial suture regeneration offers a paradigm shift in treatment to reverse skull and neurocognitive abnormalities in this devastating disease.

Long-Term Results in Isolated Metopic Synostosis: The Oxford Experience over 22 Years.

Metopic synostosis causing trigonocephaly is treated by fronto-orbital advancement and remodeling to correct the deformity and cerebral distortion and to treat intracranial hypertension in a small number of cases. The aim of this study was to evaluate complications, revisions, and long-term outcomes. A retrospective chart review was performed on consecutive metopic craniosynostosis patients treated between February of 1995 and February of 2017 at the Oxford Craniofacial Unit. Two hundred forty-five patients with isolated metopic synostosis were seen. Two hundred two patients underwent fronto-orbital advancement and remodeling. Fifty patients were girls and 152 patients were boys. Mean age at surgery was 16.8 months. Mean weight preoperatively was 12 kg. All patients received blood transfusion. Mean postoperative stay was 6 days. Average follow-up time was 8 years (range, 0.5 to 22 years). There were eight major complications (4 percent). Six patients (2.9 percent) required secondary calvarial expansion for late raised intracranial pressure. Thirty-one (15 percent) had other subsequent procedures, including wire removal and forehead shape contouring with alloplastic onlay. Raised intracranial pressure before surgery was confirmed in two cases by intracranial pressure monitoring. Trigonocephaly is caused by metopic synostosis and is treated by fronto-orbital advancement and remodeling to restore both internal and external skull configuration. After surgery, the authors identified a 2.9 percent risk of late raised intracranial pressure requiring a secondary calvarial expansion, necessitating prolonged follow-up in all cases. Temporal hollowing and forehead contour defects were not uncommon. This is the largest reported series of metopic synostosis. Therapeutic, IV.

Abstract: Reduction Cranioplasty Using Virtual Surgical Planning for Hydrocephalic Macrocephaly

INTRODUCTION: Congenital hydrocephalus, the most common cause of macrocephaly, is usually treated with ventriculoperitoneal (VP) shunting. Despite shunting, changes to the overlying cranial bones cause calvarial expansion and distortion. Reduction cranioplasty can be performed to approach proper cranial size, shape, and cephalocranial proportion. However, consistent results are difficult to achieve. Virtual surgical planning (VSP) with the creation of intraoperative templates allows for systematic control of both volume and morphology. METHODS: Four patients presented with severe hydrocephalic macrocephaly (HM). All had undergone VP shunting to control ventriculomegaly as an infant. We performed 3D CT scans and utilized VSP to obtain a post-operative cranial size/shape using age-based anatomical norms. Cutting guides and intraoperative templates were generated, and reduction cranioplasty was performed using the clinical transfer tools. Perioperative variables such as OR time, blood loss, hospital stay, and volumetric analysis were recorded. Long-term variables such as bone healing and neurocognitive development were also observed. RESULTS: All four patients recovered well after surgery. One patient had a small seroma of the scalp that resolved with aspiration and compression. All had stable reconstruction with normalized post-operative cranial morphology that followed preoperative plans. Postoperative volumes were consistent between cases. CONCLUSION: Reduction cranioplasty can be performed on patients with HM. While the concept is straightforward, achieving proper cranial morphology while respecting brain volume can be difficult. Use of VSP allows for optimization of osteotomy design while translating this plan to the final result through cutting guides and reconfiguration templates. A final cranial size and shape can be predicted to a normative cohort, allowing for precision and reliability when actuating this plan.

A New Technique for Posterior Distraction in Craniosynostosis

Posterior cranial vault distraction osteogenesis is a common treatment for syndromal patients of brachycephaly and oxycephaly. Although posterior distraction can increase intracranial volume, the flattened head phenotype is difficult to correct. The authors examined a new posterior distraction technique termed double-door distraction for improvement of the flattened head phenotype. From 2010 to 2013, 6 patients with flattened posterior craniums were operated on using the double-door distraction technique. The calvarial segment was cut at the midline and divided into 2 pieces. Distractors were then fixed in parallel to join the calvarial pieces. The distraction was initiated at a rate of 1.0 mm/day and continued until proper cranial form was confirmed by radiography and appearance. The average surgery time was 2 hours 47 minutes and the amount of distraction ranged from 15 to 22 mm. An improved head shape and expanded cranial vault was achieved in all patients without any complications. The double-door distraction technique is a useful technique not only for calvarial expansion, but also for correction of the flattened posterior cranium phenotype.

Characteristics of Postnatal Progressive Pansynostosis

INTRODUCTION: Postnatal progressive pansynostosis (PPP) is uncommon. The insidious onset and relatively normal cranial shape often leads to delay in or failure of diagnosis. The risk of increased intracranial pressure (ICP) is significant. The purpose of this study was to review our series of patients with PPP to provide a more detailed description of this form of synostosis. METHODS: The authors reviewed their ongoing prospective craniofacial database (2/97-7/12) to document patients with PPP. Variables included age at diagnosis, syndromic association, head shape, serial head circumference (HC), radiographic findings, and operative interventions. Inclusion criteria included: 1) complete or partial fusion of all major cranial sutures on high resolution CT scan; 2) no prior craniofacial procedures at the time of CT diagnosis. RESULTS: A total of 10 out of 292 patients (3.5%) were identified. Each patient had confirmed fusion of all major cranial sutures. Mean age at diagnosis was 59.4 ± 42.3 months (range: 19-151 months). A syndrome was documented in 60% of patients, with Crouzon syndrome being most common (3 patients). Head shape was reported as normal or near normal in all patients. Serial HC, available in 90% of patients, documented sustained growth deceleration at the time of diagnosis. All patients had signs of increased ICP, such as severe endocortical erosion and loss of cisternal spaces; 6/7 patients with MRI had Chiari malformation. ICP monitoring in 4 patients revealed pressures ranging from 5 to >35 cm H2O. Calvarial expansion was performed in 70% of patients, two are awaiting definitive surgical repair, and one patient had only Chiari decompression and clinical monitoring. CONCLUSION: The gradual progression of fusion in PPP results in a slow decrease in head circumference percentile and a relatively normal head shape, leading to delayed diagnosis and increased ICP. There should be a high clinical index of suspicion in children with a known craniosynostosis syndrome (especially Crouzon syndrome) and normal head shape. Any sustained deceleration in serial HC should prompt CT evaluation.

Ectocranial suture fusion in primates: as related to cranial volume and dental eruption

Timing of calvarial suture fusion is important in primate ontogeny. Ages at death are difficult to assess especially for museum collections. 1550 skulls of Hominoid, Hylobatidae, Macaca and Papio were observed for fusion. Calvarial expansion (early) and dental eruption (late) were utilized as indicators of ontogeny. Homogeneity of slopes and ANOVA were used to determine differences in timing of fusion. For calvarial growth the great apes all showed small levels of calvarial suture remodeling prior to full calvarial expansion. For dental eruption, Homo and Macaca share a common pattern of fusion in late adulthood. The other species show early remodeling. Papio was observed to have distinct patterns for suture fusion progression. Thus, suture fusion progression although influenced by evolutionary changes in the robusticity of the craniofacial skeleton can be modeled by the phylogeny among this group. Overall, Homo appears to have a distinct pattern of delayed suture fusion progression.

Posterior calvarial distraction in craniosynostosis – An evolving technique

BackgroundPosterior advancement of the occiput is an established surgical option for the treatment of raised intracranial pressure (ICP) secondary to craniocerebral disproportion in syndromic craniosynostoses. Distraction osteogenesis has gained popularity in a variety of craniofacial procedures to achieve greater advancement in the anterior craniofacial skeleton, but has only relatively recently been used in the posterior calvarium. We report the Oxford Craniofacial Unit’s experience of using distraction techniques to expand the occiput. MethodsWe preformed a retrospective casenote review of all patients with syndromic craniosynostoses who underwent posterior distraction at our centre from 2007 to 2010, as identified by the Oxford Craniofacial Database. ResultsTen syndromic patients underwent posterior distraction (mean age of 18.1months). Successful calvarial expansion (mean advancement of 19.7mm) was achieved in all patients clinically and radiologically. There were 6 minor and 1 major complications. ConclusionsPosterior distraction was successfully performed in 10 patients including babies as young as 3months of age. It achieved a reduction in turricephaly, an improvement in the cephalic index, and a resolution of raised ICP. We have customised our surgical technique to address individual patient needs. The use of distraction techniques in the occiput appears to increase the reliability of expansion in this region.

Serial Head Circumference and Neurodevelopmental Screening after Surgical Correction for Single- and Multiple-Suture Craniosynostosis

To evaluate serial head circumference (HC) measurements and neurodevelopmental (ND) screening before and after surgical revision for craniosynostosis. Retrospective assessment. Tertiary institutional. All children treated with single-stage frontal-orbital advancement or total calvarial expansion for single-suture (SS) or multiple-suture (MS) craniosynostosis over a 7-year period. Changes in ND and HC were measured over postoperative visits after the primary surgery. More importantly, ND and HC changes were measured prerevision and postrevision. Of 183 patients undergoing primary surgery, complete records and adequate follow-up were available for 112 patients. The overall revision rate was 21% (n = 23). Postrevision follow-up was adequate for 18 of the 23 revisions. After primary surgery, but prior to revision, children demonstrated a larger decline in HC (z-score, median = -1) along with higher ND findings (median = 2) from one postoperative visit to the next than those who did not go on revision (HC z-score median = 0, ND median = 0). After revision, patients demonstrated a significant improvement in ND screening findings (median ΔND findings = -2) compared with prerevision ND (p < .001). Head circumference also significantly increased by a z-score of +1 postrevision (p = .001). Patients chosen for revision surgery display not only a larger decline in HC but also more ND findings prior to revision. Furthermore, surgical revision has a significant association with both improved ND screening and HC.

Posterior calvarial vault expansion using distraction osteogenesis

Management of raised intracranial pressure in syndromic multi-suture craniosynostosis by cranial vault expansion can be achieved by a number of techniques. We present our initial experience in treating this group of patients with posterior calvarial distraction. Six patients underwent distraction osteogenesis of their posterior calvarial vault. The mean period of distraction was 28 days. The mean consolidation period was 49 days. The mean distance of advancement was 24 mm. Five out of six patients completed their period of distraction and three of these cases also completed their period of consolidation. Significant calvarial expansion and improvement of head shape was achieved in all cases. Posterior calvarial distraction is a safe and more efficient method of calvarial expansion than conventional techniques. These are early promising results, and future modification of the distraction devices will be needed if the effective consolidation time is to be increased.

Tissue Engineering: Growing Skull with In Situ Osteogenesis

Introduction Acquired skull defects are common as a result of trauma infection and calvarial expansion among other causes. The techniques available to repair these defects have included a variety of foreign body implants or bone grafting from proximal or distant sites. Tissue engineering using bone morphogenetic protein (rBMP) and an absorbable mesh scaffold offers a unique opportunity to fill defects with in situ osteogenesis. Methods Bony calvarial defects in 19 children ranging in age from 11 months to 15 years were repaired using rBMP and a collagen scaffold plus a synthetic hydroxyapatite ceramic in a granular or matrix form. The construct is held with poly D,L-lactide acid resorbable mesh. The skull defects were a result of trauma (n = 5) craniotomy for tumor (n = 2), congenital absence (n = 1), infection (n = 4), and calvarial expansion for synostosis (n = 7). The reconstruction technique varied with the size and geometry of the defect. The defects repaired ranged from 10 to 60 cm2. Results of the repair were judged by physical exam and 3D computed tomography. Results In 18 patients followed for at least 6 months, the calvarium was completely ossified in 15 cases and had a small residual defect (2 cm2) in 3 from early in the series. Two surgeries were required to completely reconstruct a bifrontal bone flap. Conclusion BMP shows promise for repairing significant calvarial defects by promoting the growth of the patient's own bone in situ osteogenesis, thereby avoiding the need for foreign body implants or bone grafts from other sites.

A computer-based method for comparisons of continuous intracranial pressure recordings within individual cases.

This study assessed two strategies of comparing continuous intracranial pressure (ICP) recordings within individual cases, namely either by calculation of differences in mean ICP or by calculation of differences in numbers of ICP elevations. Continuous ICP recordings before and after cranial surgery were both presented as mean ICP and as numbers of ICP elevations of different levels (20 and 25 mmHg lasting either 0.5 or 1 minute). Since the length of pressure recordings differed somewhat between individuals, the numbers of ICP elevations were standardised by computing the numbers of elevations during a 10 hours period. The ICP recordings were analysed by the Sensometrics Pressure Analyser software. The ICP curves included here were selected from a group of 15 children undergoing calvarial expansion surgery for craniosynostosis, in whom continuous ICP monitoring was performed both before and after surgery as part of the diagnostic workout to rule out lasting intracranial hypertension. After surgery, mean ICP during sleep was reduced by 5 mmHg or more in 5 cases, minimally changed (i.e. 2 mmHg or less) in 6 cases, and variably increased in the other 4 cases. In one of these 4 latter cases, numbers of ICP elevations were increased after surgery, but in all other 14 cases the numbers of ICP elevations were significantly reduced. Reduction of mean ICP by more than 2 mmHg associated with good outcome was observed in 3 of 15 cases (20%), whereas marked and significant reductions in numbers of ICP elevations during sleep combined with good outcome was observed in 12 of 15 cases (80%). Outcome after the 2nd ICP monitoring was more reliably predicted by computing differences in numbers of ICP elevations than by calculation of mean ICP.

The use of a resorbable plating system for treatment of craniosynostosis

Purpose: The purpose of this study was to evaluate the effectiveness of a resorbable plating system (Lactosorb; Walter Lorenz Surgical, Inc, Jacksonville, FL) as a fixation method in the treatment of craniosynostosis. Patients and Methods: Ten children with 15 affected sutures underwent craniotomies ranging from release of 1 suture to total calvarial reconstruction. The 1.5 Lactosorb plating system was used as the method of fixation in all cases. Patients were evaluated clinically and with computed tomography scans before discharge postoperatively, and at the 3-, 6-, and 9-month intervals. Results: In all 10 cases there was no evidence of neosynostosis, malposed osseous segments, or restriction of growth or calvarial expansion. In addition, none of the complications seen with more traditional techniques were evident in these patients. Conclusion: Resorbable plating systems provide a viable alternative to the more traditional fixation techniques that have been used to treat craniosynostosis and craniofacial dysostosis. © 2001 American Association of Oral and Maxillofacial Surgeons

Changes in Intracranial Pressure after Calvarial Expansion Surgery in Children with Slit Ventricle Syndrome

The effect of calvarial expansion on symptom relief and intracranial pressure (ICP) in three children with slit ventricle syndrome (SVS) and intracranial hypertension despite a functioning ventricular shunt is reported. These children presented with a clinical picture of SVS, accompanied by slit-like ventricles on cranial computer tomography scan and intracranial hypertension. Calvarial expansion was performed by mans of an anterior approach in one case and a posterior approach (modified tiara plastic) in the other two cases. After calvarial expansion, symptoms of intracranial hypertension were abolished in one case and markedly reduced in two cases (observation period 25–36 months). Comparison of ICP before and after surgery was performed by means of new software (Sensometrics™ Pressure Analyser, version 1.2) that revealed a significant reduction in the number of abnormal ICP elevations after surgery. The results were not accompanied by changes in the size of the cerebral ventricles. This study demonstrates that in children with SVS and intracranial hypertension despite a functioning shunt, calvarial expansion may reduce ICP and produce long-lasting symptom relief. In these cases, we suggest that intracranial hypertension was caused by compromised intracranial volume.

Advances In Murine Cranial Suture Research

Craniosynostosis is a pathologic condition that results from premature fusion of one or more cranial sutures. It occurs in approximately 1:2000 live births. Since the brain expands rapidly in the first few years of life, premature closure of a cranial suture leads to compensatory calvarial expansion in a plane parallel to the fused suture. Untreated, craniosynostosis can cause a characteristic dysmorphic calvarial shape, midface hypoplasia, and can lead to deafness, blindness and mental retardation. In order to understand the dynamic mechanisms that mediate craniosynostosis, we needed to investigate the biologic processes, before, during and after suture fusion. Since clinical specimens limit our investigation to the time at which the samples are excised, we have employed murine models to examine the cascading events that lead to cranial suture fusion. These models have enabled us to dissect, isolate and understand the individual roles of the dura mater, pericranium, suture mesenchyme and osteogenic fronts.

Advances In Murine Cranial Suture Research

Craniosynostosis is a pathologic condition that results from premature fusion of one or more cranial sutures. It occurs in approximately 1:2000 live births. Since the brain expands rapidly in the first few years of life, premature closure of a cranial suture leads to compensatory calvarial expansion in a plane parallel to the fused suture. Untreated, craniosynostosis can cause a characteristic dysmorphic calvarial shape, midface hypoplasia, and can lead to deafness, blindness and mental retardation. In order to understand the dynamic mechanisms that mediate craniosynostosis, we needed to investigate the biologic processes, before, during and after suture fusion. Since clinical specimens limit our investigation to the time at which the samples are excised, we have employed murine models to examine the cascading events that lead to cranial suture fusion. These models have enabled us to dissect, isolate and understand the individual roles of the dura mater, pericranium, suture mesenchyme and osteogenic fronts.

MR of craniocerebral hemiatrophy

The magnetic resonance (MR) findings of three patients with cerebral hemiatrophy, the so-called Dyke-Davidoff-Masson syndrome, which is characterized by variable degrees of unilateral loss of cerebral volume and compensatory changes of the calvarium are presented. The condition was due to middle cerebral artery stroke in all patients. The pathologic alterations of cerebral tissue and the brainstem were reflected in detail on the MR studies. MR findings in addition to the primary vascular insult included prominence of the cortical sulci and perimesencephalic cistern in one subject with acquired infarction, but an absence of such generalized sulcal prominence in two cases of congenital infantile paralysis. Otherwise the secondary ipsilateral pathologic observations were quite similar in the patients with congenital and acquired ischemic disease and encompassed a unilaterally small cerebral hemisphere together with ipsilateral diploic calvarial expansion, elevation of the petrous bone and orbital roof, and hypoplasia/atrophy of the cerebral peduncle. Although computed tomography (CT) and MR are complimentary, it is felt that MR represents the imaging procedure of choice with respect to the asessment of the etiology and extent of cerebral parenchymal involvement in patients presenting with a clinical combination of congenital or early onset of seizures, hemiparesis/plegia, and/or cranicfacial asymmetry.

Antimigraine treatment for slit ventricle syndrome

Slit ventricle syndrome is characterized by chronic or recurring headaches associated with subnormal ventricular volume in patients who have undergone shunt treatment for hydrocephalus. There appear to be at least three pathophysiological mechanisms that cause this syndrome: 1) intermittent shunt malfunction; 2) intracranial hypotension; and 3) paroxysms of increased intracranial pressure in the presence of normal shunt function. To treat seven patients with slit ventricle syndrome caused by paroxysms of elevated intracranial pressure, we successfully used antimigraine therapy rather than standard calvarial expansion procedures. None of these patients has required shunt revision or calvarial expansion during a mean follow-up period of 2 years. The symptoms of slit ventricle syndrome may be a form of "acquired" migraine in shunt patients. We suggest that, in clinically stable patients with normal shunt function, treatment against migraine may stabilize symptoms resulting from paroxysms of increased intracranial pressure. Such treatment may prevent unnecessary shunt revisions and/or calvarial expansion procedures.

Antimigraine Treatment for Slit Ventricle Syndrome

Abstract Slit ventricle syndrome is characterized by chronic or recurring headaches associated with subnormal ventricular volume in patients who have undergone shunt treatment for hydrocephalus. There appear to be at least three pathophysiological mechanisms that cause this syndrome: 1) intermittent shunt malfunction: 2) intracranial hypotension: and 3) paroxysms of increased intracranial pressure in the presence of normal shunt function. To treat seven patients with slit ventricle syndrome caused by paroxysms of elevated intracranial pressure, we successfully used antimigraine therapy rather than standard calvarial expansion procedures. None of these patients has required shunt revision or calvarial expansion during a mean follow-up period of 2 years. The symptoms of slit ventricle syndrome may be a form of “acquired” migraine in shunt patients. We suggest that, in clinically stable patients with normal shunt function, treatment against migraine may stabilize symptoms resulting from paroxysms of increased intracranial pressure. Such treatment may prevent unnecessary shunt revisions and/or calvarial expansion procedures.