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The Veterinary Clinics of North... Jul 2024This article discusses the laser-assisted turbinectomy (LATE) procedure and indications for its performance in dogs suffering from brachycephalic obstructive airway... (Review)
Review
This article discusses the laser-assisted turbinectomy (LATE) procedure and indications for its performance in dogs suffering from brachycephalic obstructive airway syndrome (BOAS). The article summarizes landmark works that reported, for the first time, endoscopic-assisted identification and treatment of structures within the brachycephalic nose that contribute to intranasal obstruction and resistance to breathing, specifically hypertrophic and aberrant nasal turbinates. Brachycephaly is discussed in the context of how these aberrations form and how definitive treatments such as LATE and adjunctive treatments such as ala vestibuloplasty, folded flap palatoplasty, and others may ameliorate the negative effects and improve patient outcomes associated with aberrant intranasal conchal configurations.
Topics: Animals; Dogs; Turbinates; Dog Diseases; Laser Therapy; Nasal Obstruction
PubMed: 38521665
DOI: 10.1016/j.cvsm.2024.02.002 -
Nature Sep 2023Craniosynostosis is a group of disorders of premature calvarial suture fusion. The identity of the calvarial stem cells (CSCs) that produce fusion-driving osteoblasts in...
Craniosynostosis is a group of disorders of premature calvarial suture fusion. The identity of the calvarial stem cells (CSCs) that produce fusion-driving osteoblasts in craniosynostosis remains poorly understood. Here we show that both physiologic calvarial mineralization and pathologic calvarial fusion in craniosynostosis reflect the interaction of two separate stem cell lineages; a previously identified cathepsin K (CTSK) lineage CSC (CTSK CSC) and a separate discoidin domain-containing receptor 2 (DDR2) lineage stem cell (DDR2 CSC) that we identified in this study. Deletion of Twist1, a gene associated with craniosynostosis in humans, solely in CTSK CSCs is sufficient to drive craniosynostosis in mice, but the sites that are destined to fuse exhibit an unexpected depletion of CTSK CSCs and a corresponding expansion of DDR2 CSCs, with DDR2 CSC expansion being a direct maladaptive response to CTSK CSC depletion. DDR2 CSCs display full stemness features, and our results establish the presence of two distinct stem cell lineages in the sutures, with both populations contributing to physiologic calvarial mineralization. DDR2 CSCs mediate a distinct form of endochondral ossification without the typical haematopoietic marrow formation. Implantation of DDR2 CSCs into suture sites is sufficient to induce fusion, and this phenotype was prevented by co-transplantation of CTSK CSCs. Finally, the human counterparts of DDR2 CSCs and CTSK CSCs display conserved functional properties in xenograft assays. The interaction between these two stem cell populations provides a new biologic interface for the modulation of calvarial mineralization and suture patency.
Topics: Humans; Mice; Animals; Craniosynostoses; Osteogenesis; Cell Lineage; Phenotype; Stem Cells
PubMed: 37730988
DOI: 10.1038/s41586-023-06526-2 -
Biological Reviews of the Cambridge... Oct 2023Cranial bones constitute a protective shield for the vulnerable brain tissue, bound together as a rigid entity by unique immovable joints known as sutures. Cranial... (Review)
Review
Cranial bones constitute a protective shield for the vulnerable brain tissue, bound together as a rigid entity by unique immovable joints known as sutures. Cranial sutures serve as major growth centres for calvarial morphogenesis and have been identified as a niche for mesenchymal stem cells (MSCs) and/or skeletal stem cells (SSCs) in the craniofacial skeleton. Despite the established dogma of cranial bone and suture biology, technological advancements now allow us to investigate these tissues and structures at unprecedented resolution and embrace multiple novel biological insights. For instance, a decrease or imbalance of representation of SSCs within sutures might underlie craniosynostosis; dural sinuses enable neuroimmune crosstalk and are newly defined as immune hubs; skull bone marrow acts as a myeloid cell reservoir for the meninges and central nervous system (CNS) parenchyma in mediating immune surveillance, etc. In this review, we revisit a growing body of recent studies that explored cranial bone and suture biology using cutting-edge techniques and have expanded our current understanding of this research field, especially from the perspective of development, homeostasis, injury repair, resident MSCs/SSCs, immunosurveillance at the brain's border, and beyond.
Topics: Humans; Skull; Cranial Sutures; Craniosynostoses; Morphogenesis; Sutures
PubMed: 37171117
DOI: 10.1111/brv.12975 -
Animals : An Open Access Journal From... Jun 2023Brachycephalic dogs are not only affected by brachycephalic obstructive airway syndrome (BOAS), but are also frequently referred to veterinary dermatologists for skin... (Review)
Review
Brachycephalic dogs are not only affected by brachycephalic obstructive airway syndrome (BOAS), but are also frequently referred to veterinary dermatologists for skin conditions, with English bulldogs and pugs particularly over-represented. Some skin diseases, such as skin fold dermatitis, are directly associated with the abnormal anatomic conformation of brachycephalic dogs, while for others, such as atopic dermatitis and viral pigmented plaques, there is an underlying genetic basis or a general predisposition. Anatomic alterations associated with brachycephaly, leading to fold formation of the skin and stenosis of the ear canal, together with primary immunodeficiencies described in some breeds, favor the development of pyoderma, dermatitis, and otitis externa/media. In addition, the frequently neglected but often lifelong dermatological problems of brachycephalic dogs are an important consideration when discussing genetic and medical conditions affecting the welfare of those dogs. Here we review the current state of knowledge concerning dermatological problems in brachycephalic dogs and combine it with clinical experience in the management of these challenging disorders.
PubMed: 37370526
DOI: 10.3390/ani13122016 -
Facial Plastic Surgery Clinics of North... Feb 2024We describe the investigation and management of select pediatric craniofacial disorders their recent advances. Positional plagiocephaly: The incidence of positional... (Review)
Review
We describe the investigation and management of select pediatric craniofacial disorders their recent advances. Positional plagiocephaly: The incidence of positional plagiocephaly has increased since the institution of the "safe to sleep" campaign to reduce sudden infant death syndrome. Positional plagiocephaly may be associated with underlying developmental delay. Nonsyndromic craniosynostosis: Treatment of nonsyndromic craniosynostosis depends on the age of the patient and the suture involved. Pediatric skull lesions: Management of skull lesions depends on histologic diagnosis. Some benign skull lesions are managed conservatively, whereas erosive and malignant lesions may require surgical excision, radiotherapy, chemotherapy, or multimodality treatment.
Topics: Infant; Humans; Child; Plagiocephaly, Nonsynostotic; Skull; Combined Modality Therapy; Craniosynostoses; Neurosurgical Procedures
PubMed: 37981408
DOI: 10.1016/j.fsc.2023.06.004 -
The Journal of Clinical Investigation Nov 2023Skull development coincides with the onset of cerebrospinal fluid (CSF) circulation, brain-CSF perfusion, and meningeal lymphangiogenesis, processes essential for brain...
Skull development coincides with the onset of cerebrospinal fluid (CSF) circulation, brain-CSF perfusion, and meningeal lymphangiogenesis, processes essential for brain waste clearance. How these processes are affected by craniofacial disorders such as craniosynostosis are poorly understood. We report that raised intracranial pressure and diminished CSF flow in craniosynostosis mouse models associate with pathological changes to meningeal lymphatic vessels that affect their sprouting, expansion, and long-term maintenance. We also show that craniosynostosis affects CSF circulatory pathways and perfusion into the brain. Further, craniosynostosis exacerbates amyloid pathology and plaque buildup in Twist1+/-:5xFAD transgenic Alzheimer's disease models. Treating craniosynostosis mice with Yoda1, a small molecule agonist for Piezo1, reduces intracranial pressure and improves CSF flow, in addition to restoring meningeal lymphangiogenesis, drainage to the deep cervical lymph nodes, and brain-CSF perfusion. Leveraging these findings, we show that Yoda1 treatments in aged mice with reduced CSF flow and turnover improve lymphatic networks, drainage, and brain-CSF perfusion. Our results suggest that CSF provides mechanical force to facilitate meningeal lymphatic growth and maintenance. Additionally, applying Yoda1 agonist in conditions with raised intracranial pressure and/or diminished CSF flow, as seen in craniosynostosis or with ageing, is a possible therapeutic option to help restore meningeal lymphatic networks and brain-CSF perfusion.
Topics: Mice; Animals; Glymphatic System; Brain; Lymphatic Vessels; Perfusion; Craniosynostoses; Drainage; Ion Channels
PubMed: 37917195
DOI: 10.1172/JCI171468 -
Cell Stem Cell Nov 2023The meninges lie in the interface between the skull and brain, harboring lymphatic vasculature and skull progenitor cells (SPCs). How the skull and brain communicate...
The meninges lie in the interface between the skull and brain, harboring lymphatic vasculature and skull progenitor cells (SPCs). How the skull and brain communicate remains largely unknown. We found that impaired meningeal lymphatics and brain perfusion drive neurocognitive defects in Twist1 mice, an animal model of craniosynostosis recapitulating human Saethre-Chotzen syndrome. Loss of SPCs leads to skull deformities and elevated intracranial pressure (ICP), whereas transplanting SPCs back into mutant mice mitigates lymphatic and brain defects through two mechanisms: (1) decreasing elevated ICP by skull correction and (2) promoting the growth and migration of lymphatic endothelial cells (LECs) via SPC-secreted vascular endothelial growth factor-C (VEGF-C). Treating Twist1 mice with VEGF-C promotes meningeal lymphatic growth and rescues defects in ICP, brain perfusion, and neurocognitive functions. Thus, the skull functionally integrates with the brain via meningeal lymphatics, which is impaired in craniosynostosis and can be restored by SPC-driven lymphatic activation via VEGF-C.
Topics: Mice; Humans; Animals; Vascular Endothelial Growth Factor C; Endothelial Cells; Skull; Meninges; Craniosynostoses; Stem Cells
PubMed: 37863055
DOI: 10.1016/j.stem.2023.09.012 -
Current Eye Research Oct 2023To summarize the ophthalmic manifestations of unilateral coronal synostosis patients. (Review)
Review
PURPOSE
To summarize the ophthalmic manifestations of unilateral coronal synostosis patients.
METHODS
We performed a literature search in the electronic database of PubMed, CENTRAL, Cochrane, and Ovid Medline guided by Preferred Reporting Items for Systematic Reviews and Meta-Analysis Statement for studies evaluating ophthalmic manifestations of unilateral coronal synostosis.
RESULTS
Unilateral coronal synostosis, also called unicoronal synostosis, may be mistaken for deformational plagiocephaly, an asymmetric skull flattening common in newborns. Characteristic facial features, however, distinguish the two. Ophthalmic manifestations of unilateral coronal synostosis include a "harlequin deformity", anisometropic astigmatism, strabismus, amblyopia, and significant orbital asymmetry. The astigmatism is greater on the side opposite the fused coronal suture. Optic neuropathy is uncommon unless unilateral coronal synostosis accompanies more complex multi-suture craniosynostosis. In many cases, surgical intervention is recommended; without intervention, skull asymmetry and ophthalmic disorders tend to worsen with time. Unilateral coronal synostosis can be managed by early endoscopic stripping of the fused suture and helmeting through a year of age or by fronto-orbital-advancement at approximately 1 year of age. Several studies have demonstrated that anisometropic astigmatism, amblyopia, and severity of strabismus are significantly lower after earlier intervention with endoscopic strip craniectomy and helmeting compared to treatment by fronto-orbital-advancement. It remains unknown whether the earlier timing or the nature of the procedure is responsible for the improved outcomes. As endoscopic strip craniectomy can only be performed in the first few months of life, early recognition of the facial, orbital, eyelid, and ophthalmic characteristics by consultant ophthalmologists enables expeditious referral and optimized ophthalmic outcomes.
CONCLUSION
Timely identification of craniofacial and ophthalmic manifestations of infants with unilateral coronal synostosis is important. Early recognition and prompt endoscopic treatment appears to optimize ocular outcomes.
Topics: Infant, Newborn; Infant; Humans; Amblyopia; Astigmatism; Retrospective Studies; Craniosynostoses; Strabismus
PubMed: 37382098
DOI: 10.1080/02713683.2023.2224536 -
The Cleft Palate-craniofacial Journal :... Oct 2023The squamosal suture (SQS) joins the temporal to the parietal bones bilaterally and is a poorly described site of craniosynostosis. SQS fusion is thought to occur as... (Review)
Review
INTRODUCTION
The squamosal suture (SQS) joins the temporal to the parietal bones bilaterally and is a poorly described site of craniosynostosis. SQS fusion is thought to occur as late as the fourth decade of life and beyond; however, we have incidentally noted its presence among our pediatric patients and hypothesize that it may occur earlier in life and more frequently than previously believed.
METHODS
A retrospective review of imaging performed on pediatric patients was completed to identify patients with SQS synostosis. This included a review of clinical notes as well as computed tomography (CT) images obtained by our craniofacial clinic. Relevant patient data and imaging were reviewed.
RESULTS
Forty-seven patients were identified with SQS synostosis, 21 were female (45%). Age at the time of radiographic diagnosis was 10.1 ± 8.4 years (range 17 days to 27 years). A majority of patients had bilateral SQS synostosis (57%), with a relatively even distribution of unilateral right (23%) versus left (19%). SQS was an isolated finding (no other suture involvement) in 15 patients (32%), all of whom were normocephalic and did not require surgical intervention. Thirty-two patients (68%) had concomitant craniosynostosis of other sutures, most commonly sagittal and coronal. Nine patients (19%) underwent surgery to correct cranial malformations-all these patients had multi-suture synostosis ( = 0.012). Twenty-seven patients (57%) had SQS synostosis diagnosed incidentally compared to 20 (43%) who were imaged with suspicion for synostosis. In those who were symptomatic, common findings included developmental delay, elevated intracranial pressure, hydrocephalus, seizures, and visual/hearing impairments. Ten patients (21%) were syndromic, the most frequent of which was Crouzon syndrome. No single pattern of calvarial malformation could be definitively described for SQS synostosis.
CONCLUSION
Given that most isolated SQS synostosis cases were normocephalic, asymptomatic, and discovered incidentally, it is likely that there are many cases of unidentified SQS synostosis. The significance of SQS synostosis is currently unclear, and warrants further investigation into this phenomenon, its natural course, and its potential presence in the spectrum of normal development.
Topics: Humans; Child; Female; Infant; Infant, Newborn; Male; Cranial Sutures; Craniosynostoses; Craniofacial Dysostosis; Retrospective Studies; Sutures
PubMed: 35593077
DOI: 10.1177/10556656221100675