O'Brien, Erin K

Background Computed tomography (CT) of the paranasal sinuses is the diagnostic reference standard for chronic rhinosinusitis and related inflammatory sinus pathology. Nasal nitric oxide (nNO) levels have been investigated as a diagnostic tool in sinus disease because it decreases with sinus obstruction. Objective The primary aim of the study was to determine the correlation of passive (baseline) and dynamic (humming) nNO to CT findings of sinus inflammation and to sinonasal symptoms measured by the modified Sinonasal Outcome Test (26 items) (SNOT-26). Methods From June 2015 through January 2016, subjects had baseline and humming nNO levels measured with a chemiluminescence NO analyzer, and each subject underwent CT imaging and completed the SNOT-26 survey. CT images were scored using the Lund–Mackay (LM) system (LM scores >3 indicated sinus inflammation). Correlation was measured by linear and ordinal regression analysis that compared SNOT-26 scores, LM scores, and nNO measurements. Results Fourteen subjects were recruited. LM scores had a positive pairwise correlation with total SNOT-26 scores ( R 2 = .1457; correlation = .3817) and nasal-specific SNOT-26 scores ( R 2 = .4036; correlation = .6353). Baseline nasal nNO scores had a negative pairwise correlation with LM scores ( R 2 = .1580; correlation = −.3582), total SNOT-26 scores ( R 2 = .1515; correlation = −.3893), and nasal-specific SNOT-26 scores ( R 2 = .0805; correlation = −.4343). Although baseline nNO levels correlated with LM and SNOT-26 scores, humming nNO levels did not show a similar correlation. Conclusion Baseline passive nNO may be a useful and inexpensive point-of-care screening test for sinonasal opacification.

Abstract Dural membrane is an important anatomic structure that surrounds and protects the entire central nervous system. Physical properties of the dura have many pathophysiological and therapeutic implications in cranial surgery, especially skull base disorders. The aim of this study is to investigate variation in skull base dural thickness and correlation with different demographic parameters. At the time of autopsy, the petrous apex dura with the underlying bone of 20 cadavers was harvested. Dural thickness was independently measured by two pathologists at the thinnest and thickest segments in the specimen. Correlational analyses were then performed to compare dural thickness with gender, age, neck circumference, height, weight, and body mass index (BMI). Mean, minimum, and maximum skull base dural thickness in our study was 0.36, 0.27, and 0.46 mm, respectively. Age demonstrated a negative correlation with dural thickness with significantly thinner dura in the older subjects, p = 0.01. There was a trend toward thinner dura in females that approached statistical significance, p = 0.06. No strong correlation could be found with body weight, height, neck circumference, or BMI. Our findings show a considerable intersubject and intrasubject variability in skull base dural thickness. Some demographic parameters also seem to impact dural thickness. Additional histological studies are needed for better understanding of the pathophysiological mechanisms pertaining to the tensile properties of the dural membrane.

ObjectiveTo define relationships between the frontal sinus opening, ostia of other frontal recess cells, and endoscopic landmarks and to develop a clinically useful framework to guide frontal sinus surgery.Study DesignRetrospective review.SettingTertiary care academic referral center.MethodsAdult patients with computed tomography (CT) without sinonasal pathology were included. Virtual endoscopy (using OsiriX) and corresponding CT reconstructions were used to identify all visible ostia in the frontal recess and characterize their positions in spaces between the uncinate/agger nasi (U), bulla ethmoidalis (EB), and middle turbinate (MT).ResultsTwo hundred sides in 100 patients (median age 51 years, 62% female) were analyzed. The “center” of each map was defined as the intersection of spaces between U, EB, and MT. The frontal sinus opening was in the “center” in 53% of frontal recesses, lateral to this position in 29%, and anterior in 11%. When the frontal sinus opening was at the “center,” anterior ostia drained frontal Kuhn T cells in 51% and intersinus septal cells in 23%. The skull base attachment of the apical strut of the uncinate process demarcated medial and lateral within the space between U and EB, with the opening to the frontal sinus medial in 68% and lateral in 31%. Left‐right asymmetry in frontal sinus openings was noted in 46% of patients.ConclusionCombining preoperative imaging and knowledge of these anatomic relationships may facilitate more efficient frontal outflow tract identification and instrumentation. This represents the first and largest description of ostial configurations relative to endoscopic structural landmarks.Level of Evidence:4

Objective/HypothesisEosinophilic otitis media (EOM) is a variant of chronic otitis media that is characterized by the development of thick mucoid middle ear effusion, adult onset bronchial asthma, sinonasal polyposis, and aspirin sensitivity. EOM is typically refractory to corticosteroid therapy and surgical intervention. Pegylated interferon (PEG‐IFN) has effectively treated hypereosinophilic syndrome in clinical trials; however, the efficacy of this medication for EOM treatment remains undefined.Study DesignRetrospective, case series, tertiary academic center.MethodsA retrospective chart review was performed on EOM patients from 2008–2014. A total of 32 patients met the clinical criteria for EOM according to established diagnostic guidelines. Outcomes of all patients with severe, refractory EOM who initiated PEG‐IFN therapy are reported.ResultsEight patients were treated with pegylated interferon‐α 2a or 2b for refractory EOM. Half of the patients had significant side effects with interferon treatment. Three of these were able to continue at a reduced dosage without side effect reoccurrence, and one patient stopped the medication permanently. Four of eight (50%) patients had a complete clinical response with total resolution of otorrhea and normalization of middle ear mucosa, and were able to discontinue corticosteroid treatment. Two patients attempted to stop PEG‐IFN therapy after prolonged symptom remission and had recurrent otorrhea. Both patients had symptom resolution after PEG‐IFN reinitiation.ConclusionsThese data demonstrate that pegylated interferon‐α 2a and 2b therapy may benefit patients with severe, refractory EOM. Further larger studies with long‐term follow‐up are required to validate these early but promising results.Level of Evidence4. Laryngoscope, 127:1208–1216, 2017

Background Since 1972, patients with large nasal perforations, who were symptomatic, and who were not candidates for surgery, had the option of custom prosthetic closure at Mayo Clinic. Although septal prostheses have helped many patients, 27% of pre-1982 patients chose not to keep the prosthesis in place. Two-dimensional computed tomography (CT) sizing resulted in more of the patients choosing to retain the prosthesis. The introduction of three-dimensional (3-D) printing to the sizing process offered the potential of further improved retention by refinement in prosthesis fit. Objective To describe the fabrication of nasal septal prostheses by using 3-D printing for sizing and to compare the retention rate of 3-D-sized prostheses with those that used previous sizing methods. Methods Twenty-one consecutive patients who had placement of septal prostheses sized by using 3-D printed templates were studied. CT image data were used to print 3-D templates of the exact shape of the patient's septal perforation, and medical-grade silastic prostheses were fabricated to fit. In four cases, the 3-D printed template allowed preoperative surgical simulation. Metrics collected included prosthesis retention; symptoms, including intranasal crusting and epistaxis; and previous prosthetic closure failures. Results Twenty of the twenty-one patients had improvement in symptoms. The mean diameter of the perforations was 2.4 cm; the mean closure time by the end of the study period was 2.2 years. All but two patients chose to keep their prosthesis in place, for a retention rate of 90%. Seven patients with successful closure had failed previously with prior prosthesis sized without the current 3-D printing methodology. This 90% retention rate exceeded the previous rates before the introduction of 3-D sizing. Conclusion Sizing done by 3-D printing for prosthetic closure of nasal septal perforations resulted in a higher retention rate in helping patients with these most-challenging nasal septal perforations.

OBJECT Endoscopic approaches to the anterior craniocervical junction are increasing in frequency. Choice of oral versus endoscopic endonasal approach to the odontoid often depends on the relationship of the C1–2 complex to the hard palate. However, it is not known how this relevant anatomy changes with age. We hypothesize that there is a dynamic relationship of C-2 and the hard palate, which changes with age, and potentially affects the choice of surgical approach. The aim of this study was to characterize the relationship of C-2 relative to the hard palate with respect to age and sex. METHODS Emergency department billing and trauma records from 2008 to 2014 were reviewed for patients of all ages who underwent cervical or maxillofacial CT as part of a trauma evaluation for closed head injury. Patients who had a CT scan that allowed adequate visualization of the hard palate, opisthion, and upper cervical spine (C-1 and C-2) were included. Patients who had cervical or displaced facial/skull base fractures, a history of rheumatoid arthritis, or craniofacial anomalies were excluded. The distance from McGregor's palatooccipital line to the midpoint of the inferior endplate of C-2 (McL–C2) was measured on midsagittal CT scans. Patients were grouped by decile of age and by sex. A 1-way ANOVA was performed with each respective grouping. RESULTS Ultimately, 483 patients (29% female) were included. The mean age was 46 ± 24 years. The majority of patients studied were in the 2nd through 8th decades of life (85%). Significant variation was found between McL–C2 and decile of age (p < 0.001) and sex (p < 0.001). The mean McL–C2 was 27 mm in the 1st decade of life compared with the population mean of 37 mm. The mean McL–C2 was also noted to be smaller in females (mean difference 4.8 mm, p < 0.0001). Both decile of age (p = 0.0009) and sex (p < 0.0001) were independently correlated with McL–C2 on multivariate analysis. CONCLUSIONS The relationship of C-2 and the hard palate significantly varies with respect to age and sex, descending relative to the hard palate a full centimeter on average in adulthood. These findings may have relevance in determining optimal surgical approaches for addressing pathology involving the anterior craniocervical junction.

ObjectiveAssess human papilloma virus (HPV) transcriptional activity in inverted Schneiderian papillomas (IPs).Study DesignCase series with chart review.SettingAcademic tertiary care center.Subjects and MethodsRetrospective clinicopathologic review of 19 cases of IP in patients undergoing surgical excision from 1995 to 2013 at Mayo Clinic in Rochester, Minnesota. Surgical pathology archival material was histopathologically reviewed using hematoxylin and eosin–stained slides. Formalin‐fixed, paraffin‐embedded material from each case was evaluated for p16 expression using immunohistochemistry as well as HPV DNA and E6/E7 messenger RNA (mRNA) transcription using polymerase chain reaction (PCR) and in situ hybridization (via RNAscope technology), respectively.ResultsEight patients were female (42%), with an average age of 53 years (range, 23‐82 years). Three demonstrated malignancy, and 5 subsequently recurred. Average follow‐up was 49 months (range, 0‐200 months), and 1 patient died from squamous cell carcinoma arising from the IP. RNAscope detected HPV mRNA transcripts exclusively within IP in 100% of cases; however, in 11 patients (58%), less than 1% of cells exhibited transcriptional activity. Only 2 of 19 cases (11%) demonstrated mRNA activity in 50% or more cells. HPV DNA was detected in only 2 specimens by PCR.ConclusionsThis study reveals wide prevalence but limited transcriptional activity of HPV in IP. No correlation between HPV transcriptional activity and progression, recurrence, or malignant transformation was identified. These data suggest that transcription of HPV may contribute to the pathogenesis of IP, but prospective data are needed to definitively demonstrate this connection. These results also suggest that RNAscope may be more sensitive than PCR in detecting HPV activity in IP.

Objectives: This case presents a previously undescribed clinical scenario of spontaneous cerebrospinal fluid (CSF) leaks secondary to a lateral sphenoid sinus recess skull base dehiscence and contralateral Sternberg’s canal. This case report aims to characterize the presentation and successful management of these lesions. Methods: The electronic medical record was used to collect information pertaining to the patient’s clinical history. Results: The patient was a middle-aged, obese female with persistent clear rhinorrhea as her only presenting symptom. Neuroradiologic studies localized the defect to the lateral sphenoid sinus recess. CSF opening pressures were within normal limits, but radiographic findings were consistent with elevated intracranial pressure. After an endoscopic transnasal transsphenoidal approach failed to resolve the CSF leak, a transpterygoid approach facilitated CSF leak resolution. The patient then did well for the following 2 years, but later developed a CSF leak through a contralateral Sternberg’s canal. An endoscopic suprapterygoid procedure and ventriculoperitoneal shunt placement led to CSF leak resolution. Conclusion: This case demonstrates one of the only published examples of a sphenoid sinus CSF leak secondary to Sternberg’s canal as it was originally described in the literature. Wide endoscopic surgical exposure and intracranial pressure management ultimately led to CSF leak resolution.

SummaryBackgroundThe mechanisms and immune pathways associated with chronic rhinosinusitis (CRS) are not fully understood. Immunological changes during acute exacerbation of CRS may provide valuable clues to the pathogenesis and perpetuation of the disease.ObjectiveTo characterize local and systemic immune responses associated with acute worsening of sinonasal symptoms during exacerbation in CRS with nasal polyps (CRSwNP) compared to controls.MethodsThis was a non‐interventional prospective study of individuals with CRSwNP and normal controls. Subjects underwent a baseline visit with collection of nasal secretions, nasal washes, and serum specimens. Within 3 days of acute worsening of sinonasal symptoms, subjects underwent a study visit, followed by a post‐visit 2 weeks later. The sinonasal outcome test‐22 (SNOT‐22) scores and immunological parameters in the specimens were analysed using a novel, unsupervised learning method and by conventional univariate analysis.ResultsBoth CRSwNP patients and control subjects showed a significant increase in SNOT‐22 scores during acute exacerbation. Increased nasal levels of IL‐6, IL‐5, and eosinophil major basic protein were observed in CRSwNP patients. A network analysis of serum specimens revealed changes in a set of immunological parameters, which are distinctly associated with CRSwNP but not with controls. In particular, systemic increases in VEGF and GM‐CSF levels were notable and were validated by a conventional analysis.ConclusionsCRSwNP patients demonstrate distinct immunological changes locally and systemically during acute exacerbation. Growth factors VEGF and GM‐CSF may be involved in the immunopathogenesis of subjects with CRS and nasal polyps experiencing exacerbation.

Object Swallowing dysfunction is common following transoral (TO) odontoidectomy. Preliminary experience with newer endoscopic transnasal (TN) approaches suggests that dysphagia may be reduced with this alternative. However, the reasons for this are unclear. The authors hypothesized that the TN approach results in less disruption of the pharyngeal plexus and anatomical structures associated with swallowing. The authors investigate the histological and gross surgical anatomical relationship between pharyngeal plexus innervation of the upper aerodigestive tract and the surgical approaches used (TN and TO). They also review the TN literature to evaluate swallowing outcomes following this approach. Methods Seven cadaveric specimens were used for histological (n = 3) and gross anatomical (n = 4) examination of the pharyngeal plexus with the TO and TN surgical approaches. Particular attention was given to identifying the location of cranial nerves (CNs) IX and X and the sympathetic chain and their contributions to the pharyngeal plexus. S100 staining was performed to assess for the presence of neural tissue in proximity to the midline, and fiber density counts were performed within 1 cm of midline. The relationship between the pharyngeal plexus, clivus, and upper cervical spine (C1-3) was defined. Results Histological analysis revealed the presence of pharyngeal plexus fibers in the midline and a significant reduction in paramedian fiber density from C-2 to the lower clivus (p < 0.001). None of these paramedian fibers, however, could be visualized with gross inspection or layer-by-layer dissection. Laterally based primary pharyngeal plexus nerves were identified by tracing their origins from CNs IX and X and the sympathetic chain at the skull base and following them to the pharyngeal musculature. In addition, the authors found 15 studies presenting 52 patients undergoing TN odontoidectomy. Of these patients, only 48 had been swallowing preoperatively. When looking only at this population, 83% (40 of 48) were swallowing by Day 3 and 92% (44 of 48) were swallowing by Day 7. Conclusions Despite the midline approach, both TO and TN approaches may injure a portion of the pharyngeal plexus. By limiting the TN incision to above the palatal plane, the surgeon avoids the high-density neural plexus found in the oropharyngeal wall and limits injury to oropharyngeal musculature involved in swallowing. This may explain the decreased incidence of postoperative dysphagia seen in TN approaches. However, further clinical investigation is warranted.