Prevention of oral and maxillofacial trauma secondary to orofacial dyskinesias associated with anti-N-methyl-D-aspartate receptor encephalitis: a case series.

BACKGROUND: Anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE) is a multi-stage autoimmune-mediated disease associated with a multitude of neuropsychiatric and dysautonomic features. Orofacial dyskinesias are frequently associated with this condition and manifest as abnormal movements of the orofacial musculature. These involuntary movements may result in significant trauma to the oral and maxillofacial complex including the avulsion of the dentition and orofacial lacerations. CASE PRESENTATION: We describe the course of two female patients with anti-NMDARE in whom significant involuntary self-inflicted maxillofacial trauma was suffered despite the use of complex parenteral sedation regimens. The application of traditional maxillomandibular wiring techniques and pharmacologic strategies, including botulinum toxin, to immobilize the mandible were initially unsuccessful. These difficulties led to the fabrication and wire-based fixation of a patient-specific acrylic oral appliance that maintained the mandible in a depressed position and mitigated all lateral and protrusive movements. DISCUSSION AND CONCLUSIONS: These cases illustrate the first known successful use of an appliance-based therapy for managing orofacial dyskinesias in the anti-NMDARE patient population through an adaptation of traditional maxillomandibular fixation techniques. This approach eliminated further orofacial trauma and afforded physicians with safer means to manage and assess patients afflicted with this condition during their protracted intensive care unit admissions.

TNFα Signaling Is Increased in Progressing Oral Potentially Malignant Disorders and Regulates Malignant Transformation in an Oral Carcinogenesis Model.

Oral carcinogenesis represents a multi-stage process which encompasses several genetic and molecular changes that promote the progression of oral potentially malignant disorders (OPMDs) to oral squamous cell carcinomas (OSCCs). A better understanding of critical pathways governing the progression of OMPDs to OSCCs is critical to improve oncologic outcomes in the future. Previous studies have identified an important role of tumor necrosis factor α (TNFα) and TNF receptor 1 (TNFR1) in the invasiveness of oral cancer cell lines. Here, we investigate the expression of TNFα and TNFR1 in human OPMDs that progress to OSCC compared to non-progressing OPMDs utilizing fluorescent immunohistochemistry (FIHC) to show increased TNFα/TNFR1 expression in progressing OPMDs. In order to interrogate the TNFα/TNFR1 signaling pathway, we utilized a 4-nitroquinoline 1-oxide (4-NQO) mouse model of oral carcinogenesis to demonstrate that TNFα/TNFR1 expression is upregulated in 4-NQO-induced OSCCs. TNFα neutralization decreased serum cytokines, inhibited the development of invasive lesions and reduced tumor-associated neutrophils in vivo. Combined, this data supports the role of TNFα in oral malignant transformation, suggesting that critical immunoregulatory events occur downstream of TNFR1 leading to malignant transformation. Our results advance the understanding of the mechanisms governing OSCC invasion and may serve as a basis for alternative diagnostic and therapeutic approaches to OPMDs and OSCC management.

Tissue-specific murine neutrophil activation states in health and inflammation.

Neutrophils are quickly recruited to tissues in response to proinflammatory cues; however, little is known about tissue neutrophil phenotypes in health. We employ a multicolor flow cytometric approach to assess surface markers of activation on neutrophils from the bone marrow, blood, peritoneum, spleen, liver, fat, colon, and oral cavity of healthy mice. Cell preparations were promptly fixed to preserve native surface marker expression levels. Peritoneal, colonic, and oral neutrophils were also assessed in the setting of pHrodo-induced peritonitis, dextran sodium sulfate-induced colitis, and ligature-induced periodontal disease, respectively. Our results demonstrate consistent detectable neutrophil populations in various sterile and nonsterile tissues of healthy mice, and these cells had tissue-specific neutrophil immunophenotypes. Neutrophils derived from biofilm-associated mucosal tissues had 2- to 3-fold higher expression of surface markers of activation, including CD66a, CD11b, and CD62L, compared to neutrophils derived from both sterile healthy tissues as well as tissues in animals treated with broad-spectrum antibiotics. Furthermore, the unique cluster of differentiation (CD) marker activation signatures of tissue-specific neutrophils from the peritoneum, colon, and oral cavity were altered to a proinflammatory immunophenotype with the presence of an inflammatory stimulus. Based on our results, we propose a model whereby a hierarchy of tissue neutrophil immunophenotypes, based on the differential expression of CD markers of activation, correlates with sterile, healthy commensal biofilm-associated and inflamed tissue states.

The effect of pamidronate delivery in bisphosphonate-naïve patients on neutrophil chemotaxis and oxidative burst.

The pathogenesis of medication-related osteonecrosis of the jaw (MRONJ), a morbid condition associated with bisphosphonate administration, has not been fully elucidated. Recent research utilizing a murine model has revealed that the neutrophil becomes dysfunctional following exposure to bisphosphonates. Accordingly, the impairment of neutrophil function could play an important role in the pathogenesis of MRONJ via an infectious mechanism mediated by the suppression of the innate immune system. Currently, the existing human data are insufficient to substantiate this theory. To investigate, we isolated neutrophils from blood and oral rinse samples from bisphosphonate-naïve patients who were recently diagnosed with multiple myeloma both prior to and one month following their initial infusion of pamidronate, an intravenous bisphosphonate agent. Stimulated blood and oral neutrophil superoxide production and chemotactic capabilities were found to be impaired relative to baseline values. These results suggest that impaired neutrophil function may partially contribute to the aetiology underlying the pathophysiological processes linked to the development of MRONJ. Further, as the functional status of circulating neutrophils was reflected in the oral cavity where sampling can be accomplished in a non-invasive fashion, it is conceivable that neutrophil function could serve as a potential biomarker for MRONJ prognostication.

Robust Ligature-Induced Model of Murine Periodontitis for the Evaluation of Oral Neutrophils.

The main advantages of studying the pathophysiology of periodontal disease utilizing murine models are the reduced cost of animals, array of genetically modified strains, the vast number of analyses that can be performed on harvested soft and hard tissues. However, many of these systems are subject to procedural criticisms. As an alternative, the ligature-induced model of periodontal disease, driven by the localized development and retention of a dysbiotic oral microbiome, can be employed, which is rapidly induced and relatively reliable. Unfortunately, the variants of ligature-induced murine periodontitis protocol are isolated to focal regions of the periodontium and subject to premature avulsion of the installed ligature. This minimizes the amount of tissue available for subsequent analyses and increases the number of animals required for study. This protocol describes the precise manipulations required to place extended molar ligatures with improved retention and usage of a novel rinse technique to recover oral neutrophils in mice with an alternative approach that mitigates the aforementioned technical challenges.

Primed PMNs in healthy mouse and human circulation are first responders during acute inflammation.

Polymorphonuclear neutrophils (PMNs) are the most abundant circulating leukocytes, and the first cells recruited to sites of tissue inflammation. Using a fixation method to preserve native CD marker expression prior to immunophenotyping, we identified a distinct population of "primed for recruitment" PMNs in healthy mouse and human blood that has high expression of adhesion and activation markers compared with the bulk resting-state PMNs. In response to acute tissue inflammation, primed PMNs (pPMNs) were rapidly depleted from the circulation and recruited to the tissue. One hour after acute peritoneal insult, pPMNs became the dominant PMN population in bone marrow (BM) and blood, returning to baseline levels with resolution of inflammation. PMN priming was induced by the granulopoietic factors granulocyte-macrophage-colony-stimulating factor (GM-CSF) and granulocyte-colony-stimulating factor (G-CSF). High levels of pPMNs were observed in neutropenic mice and in pediatric neutropenic patients who were resistant to infection, highlighting an important role of this population in innate immune function.

Primary aneurysmal bone cyst of the mandibular condyle with USP6-CDH11 fusion.

Primary aneurysmal bone cyst (ABC) is a cystic bone neoplasm characterized by disease-defining gene fusions involving the USP6/Tre2 gene. The literature describing gnathic ABC is limited. This case report describes a 27-year-old man presenting with a long-standing left-sided facial asymmetry. Multi-detector computed tomography imaging demonstrated a large expansile lesion positioned within the left condylar head. The lesion was biopsied and resected. The specimen showed a giant cell-rich cystic neoplasm, with fibrous tissue lined by multinucleated giant cells. Next-generation sequencing confirmed the presence of a USP6-CDH11 fusion gene, consistent with classification as a primary ABC, the first reported to be translocation-positive in the head of the mandibular condyle.

Novel Technique Using Cyanoacrylate and Local Hemostatic Agents in the Management of High-Risk Exodontia Bleeding in a Patient With a Large Facial Arteriovenous Malformation.

PURPOSE: This report describes a case of a 32-year-old woman who had been diagnosed with a facial arteriovenous malformation during childhood. Because this patient possessed a major risk of perioperative hemorrhage, the use of several local hemostatic measures was thoroughly explored before routine exodontia. MATERIALS AND METHODS: Selective embolization of the right superior thyroid artery was performed intraoperatively and a novel hemostatic technique using a combination of a packing of Gelfoam wrapped in Surgicel was placed within the extraction sites and sealed with SwiftSet. RESULTS: Local hemostasis was achieved with a novel technique using a combination of cyanoacrylate and local hemostatic agents despite aggressive hemorrhaging after routine exodontia. CONCLUSION: By exploiting the local properties of these agents, local hemostasis can be achieved with this novel technique even in the most challenging cases of vascular anomalies.

The effects of slice thickness and interslice interval on reconstructed cone beam computed tomographic images.

OBJECTIVE: The objective of this study was to compare the effects of varying 2 image-processing parameters, slice thickness and interslice interval, on the appearances of reconstructed cone beam CT (CBCT) images. STUDY DESIGN: Bone height was used a metric for comparing images reconstructed with different slice thicknesses and interslice intervals. We examined 102 putative implant sites in 18 subjects who had treatment planned for dental implants and who were imaged with custom-fitted imaging stents with linear radiopaque markers. Image slice thickness and interslice interval were increased in millimetric increments from 1 to 5 mm, and bone height was used to determine if varying these parameters had a bearing on the resulting images. RESULTS: Statistically significant differences were found between bone heights when slice thickness or interslice interval were varied by greater than 1 mm (P < .005). CONCLUSIONS: Understanding the effects of slice thickness and interslice interval may be important in the portrayal of both normal anatomy and pathoses in CBCT images.

Image distortion and magnification of 3 digital CCD cephalometric systems.

OBJECTIVE: The magnification and distortion of images made from scanning and nonscanning CCD cephalometric systems was evaluated. STUDY DESIGN: Acrylic box and dry human skull phantoms were imaged using a conventional cephalostat, the nonscanning Kodak 8000C, the horizontally scanning GE/Instrumentarium OC100D, and the vertically scanning Sirona OrthophosDS. True linear and angular measurements of the phantoms were made using a coordinate measuring system and the Hitachi MercuRay cone beam system. The accuracy of linear and angular measurements was assessed, as were magnification and distortion, where appropriate. RESULTS: Statistically significant differences between linear and angular measurements were found for almost all measurements for both phantoms. In general, the conventional cephalostat and Sirona OrthophosDS systems produced the greatest magnification and distortion while the GE/Instrumentarium OC 100D and Kodak 8000C systems, the least. CONCLUSIONS: Measurement differences related to the beam geometries of these systems could not be predicted a priori. Unaccounted for, these differences could result in clinically significant consequences.