Management of Post-Infectious Anosmia and Hyposmia: A Systematic Review.

BACKGROUND: Anosmia and hyposmia significantly affect patients' quality of life and have many etiologies, including trauma, inflammatory conditions including chronic rhinosinusitis, neoplasm, and viral infections, such as rhinovirus and SARS-CoV-2. OBJECTIVE: Our purpose was to establish whether a consensus exists regarding optimal management of olfactory dysfunction and to provide insight into the treatment of anosmia in the current climate of increased prevalence secondary to COVID-19. Thus, we aimed to systematically review the literature on the management of non-Chronic-rhinosinusitis- related anosmia/hyposmia. METHODS: PubMed, EMBASE, and Cochrane databases were searched for articles published since January 1990 using terms combined with Medical Subject Headings (MeSH). We included articles evaluating management of anosmia and hyposmia written in the English language, with original data, a minimum of 3 months of follow-up except for COVID-related studies, at least 2 patients, and well-defined and measurable outcomes. RESULTS: A total of 3013 unique titles were returned upon the initial search. Of these, 297 abstracts were examined, yielding 19 full texts meeting inclusion criteria (8 with level 1 evidence, 3 with level 2, 1 with level 3, and 7 with level 4). The studies included a total of 1522 subjects, with follow up ranging from 3 to 72 months, with an exception for COVID related studies. Endpoints were based on clinically significant improvements of olfactory functions as measured through validated smell tests. Treatments with the most robust data were intranasal corticosteroids and olfactory training. CONCLUSION: The literature on the treatment of anosmia and hyposmia includes randomized trials showing the efficacy of a few modalities. While further research is needed to expand therapeutic options for this debilitating condition, the current literature supports the use of olfactory training and topical corticosteroids.

Diagnosis of Anosmia and Hyposmia: A Systematic Review.

BACKGROUND: Anosmia and hyposmia have many etiologies, including trauma, chronic sinusitis, neoplasms, and respiratory viral infections such as rhinovirus and SARS-CoV-2. We aimed to systematically review the literature on the diagnostic evaluation of anosmia/hyposmia. METHODS: PubMed, EMBASE, and Cochrane databases were searched for articles published since January 1990 using terms combined with Medical Subject Headings (MeSH). We included articles evaluating diagnostic modalities for anosmia, written in the English language, used original data, and had two or more patients. RESULTS: A total of 2065 unique titles were returned upon the initial search. Of these, 226 abstracts were examined, yielding 27 full-text articles meeting inclusion criteria (Level of evidence ranging from 1 to 4; most level 2). The studies included a total of 13,577 patients. The most utilized diagnostic tools were orthonasal smell tests (such as the Sniffin' Sticks and the UPSIT, along with validated abridged smell tests). Though various imaging modalities (including MRI and CT) were frequently mentioned in the workup of olfactory dysfunction, routine imaging was not used to primarily diagnose smell loss. CONCLUSION: The literature includes several studies on validity and reliability for various smell tests in diagnosing anosmia. Along with a thorough history and physical, validated orthonasal smell tests should be part of the workup of the patient with suspected olfactory dysfunction. The most widely studied modality was MRI, but criteria for the timing and sequence of imaging modalities was heterogenous.

Invasive Cryptococcal Meningitis Presenting as a Skull Base Mass in An Immunocompetent Host: A Case Report.

Introduction Encephalitis due to Cryptococcus neoformans has been seen almost exclusively in patients with severe compromise of their immune systems, such as acquired immune deficiency syndrome (AIDS). Fungal sinusitis with frank invasion through the cranial base and subsequent seeding of the central nervous system is rare, but should be considered in the differential of patients presenting with meningitis and sinus/skull base lesions even without obvious immune compromise. Improvements in diagnostic testing has increased the ability to correctly identify and new antimicrobials have allowed a condition that once carried a high morbidity and mortality to be managed with better outcomes. We present our treatment algorithm for successful management of an immunocompetent patient with extensive fungal encephalitis due to erosion through the skull base. Case Description The patient is a 59-year-old male presenting unresponsive with sphenoid mass erosive of the skull base and symptoms of meningitis and encephalitis due to C. neoformans . Magnetic resonance imaging (MRI) at presentation demonstrated extensive diencephalic invasion, and a sphenoid mass with erosion of the skull base. Lumbar puncture (LP) confirmed elevated opening pressure of 45 cm H2O, and cultures confirmed infection with C. neoformans . He underwent operative sinonasal debridement followed by placement of an external ventricular drain for management of hydrocephalus. He was treated aggressively with a combination of both intravenous (IV) amphotericin B daily and intrathecal amphotericin B via the ventriculostomy thrice weekly. By the 2nd week of treatment, patient regained consciousness. After 4 weeks of therapy, cerebrospinal fluid (CSF) cultures turned negative, and the external ventricular drain (EVD) was converted to a ventriculoperitoneal shunt (VPS) to manage chronic postinfectious hydrocephalus. We also placed a contralateral Ommaya reservoir to permit continued weekly intrathecal amphotericin B without violation of the shunt valve. With each instillation, the shunt was set to its highest setting to minimize CSF egress for 6 hours then reset to its "drainage" setting. After an additional 6 weeks of outpatient therapy, intrathecal therapy was discontinued. We continued CSF surveillance via Ommaya sampling monthly. At 9-month follow-up, he has remained clinically stable without evidence of recurrent infection. He has residual mild cognitive deficits, but is living semiindependently with his brother. Conclusions Fungal sinusitis is uncommon, especially in those without significantly compromised immune systems. Invasive fungal meningitis resulting in meningitis and encephalitis is even rarer. The condition carries high morbidity and mortality that can only be mitigated with a multidisciplinary effort by neurosurgery, otolaryngology, and infectious disease specialists. While there are no clear treatment guidelines, we present an approach that may permit longer term independent survival.

Isolated sphenoid sinus opacification: A systematic review.

OBJECTIVE: Unilateral sphenoid sinus opacification (SSO) on imaging is a common incidental radiologic finding. Inflammatory sinus disease is rarely isolated to one sinus cavity therefore SSO raises the potential for neoplastic etiology. The clinical significance of SSO was evaluated and compared to maxillary sinus opacification (MSO). METHODS: A systematic review of unilateral sinus opacification was performed via Medline (1966-January 12th, 2015) and Embase (1980-January 12th, 2015), limited to English literature and human subjects. Case series of patients treated with radiologic evidence of unilateral sinus opacification either from maxillary or sphenoid sinuses and with pathology results were included. Individual cases were classified as neoplastic, malignant, or a condition requiring surgical intervention (i.e. fungal ball). Exclusion criteria were single case reports, lack of primary data, series of complications, or single pathology series. Case-by-case analysis was performed for both SSO and MSO. RESULTS: Search strategy revealed 3264 studies. A total of 31 studies including 1581 patients met the inclusion criteria. In these studies, SSO was described in n=1215 (76.9%) and MSO in n=366 (23.1%). For SSO, the final diagnosis was neoplasia 18%, (malignancy in 10.9%). 58.3% of cases required surgical intervention and 13% were inflammatory. For MSO, neoplasia represented 18.3% (malignancy 7.1%), surgical intervention required in 47% of cases and 27.6%. were inflammatory. CONCLUSION: Isolated MSO and SSO is a marker of neoplasia in 18% and malignancy in 7-10% of patients presenting with these radiologic findings. Clinicians should be wary of conservative management given the high incidence of neoplasia and consider a lower threshold for early surgical intervention.

Frontal sinus surgery and sinus distribution of nasal irrigation.

BACKGROUND: Effective mucus lavage and delivery of topical pharmaceuticals are central to successful management of chronic rhinosinusitis (CRS). The frontal sinus remains difficult to penetrate with topical therapies. This study evaluates the benefit of Draf III frontal dissection compared to traditional Draf IIa for distribution of topical therapies. METHODS: Fresh human cadaver heads were dissected sequentially with Draf IIa frontal sinusotomy and then Draf III procedures. Each cavity was irrigated with pediatric (120 mL) and adult (240 mL) irrigation bottles with 1/1000 10% fluorescein-labeled free water in 2 fixed positions (vertex and Frankfort horizontal). An endoscope at a fixed position within the frontal sinus recorded frontal sinus and frontal recess penetration. The images then underwent blinded evaluation of fluid distribution scored as 0 to 4 (nasal cavity only, frontal recess, medial one-half, lateral one-half, and lavage). Ordinal distribution score was analyzed with Kendall's tau-b. RESULTS: Eight specimens (age 76 ± 11.2 years; 50% female) were assessed. Draf III was superior to Draf IIa in ability to achieve frontal sinus distribution of irrigation (90.6% vs 50.1%, p < 0.001). Vertex head position improved distribution (90.6% vs 50.1%, p < 0.001), was synergistic with Draf III (100% with 87.5% lavage, p < 0.001), but was unable to overcome Draf IIa (81.2% with 25% lavage, p < 0.001). Irrigation volume trended toward improved distribution with larger volume irrigations. CONCLUSION: Successful treatment of sinonasal disease may require postoperative delivery of topical therapies. Draf III frontal sinusotomy achieves superior topical access, and access to the frontal sinus with Draf IIa appears limited, despite large volumes and positioning.

Long-term outcomes in medial flap inferior turbinoplasty are superior to submucosal electrocautery and submucosal powered turbinate reduction.

BACKGROUND: Techniques for inferior turbinate reduction vary from complete turbinectomy to limited cauterization. Surgical methods differ on the degree of tissue reduction and reliance on surgical tissue removal vs tissue ablation. The outcome and morbidity from 3 different turbinate techniques are compared. METHODS: A randomized double-blinded study was performed. Patient nasal cavities were randomized to different interventions on each side within the same patient. One group had a combination of submucosal powered turbinate reduction (designated "submucosal") and submucosal electrocautery (designated "electrocautery"); and the second group had a combination of submucosal powered turbinate reduction (designated "submucosal") and medial flap turbinoplasty (designated "turbinoplasty"). Patient-scored nasal obstruction and rhinorrhoea (1 to 5) along with blindly assessed nasal airway patency ratings (1 to 4) was done at 12 and 60 months postoperatively. Pain requiring additional analgesia, crusting, bleeding (needing review), and revision were documented. RESULTS: A total of 100 patients were recruited (age 32.79 ± 13.58 years; 39% female). This represented 200 nasal airway surgeries with 100 submucosal procedures, 50 electrocautery and 50 medial flap turbinoplasties. No patients complained of worsening of their obstruction. At 60 months patients in the turbinoplasty group had greater outcomes, with 90.2% having occasional or no decongestant use (Kendall's tau B p < 0.001) compared to electrocautery (15.8%) and submucosal (37.8%). Fewer turbinoplasty patients had a revision procedure (12%, χ(2) = 20.08, p < 0.001) compared to electrocautery (54%) and submucosal (40%). Crusting was more common in the electrocautery group (58% vs submucosal 2% and turbinoplasty 0%; χ(2) = 92.04; p < 0.001). CONCLUSION: The medial flap turbinoplasty provided consistent, robust results. Long-term relief of obstructive symptoms without additional risk of complication was observed in the turbinoplasty group.

The Olfactory Strip and Its Preservation in Endoscopic Pituitary Surgery Maintains Smell and Sinonasal Function.

Background The return of olfaction and of sinonasal function are important end points after pituitary surgery. Opinions differ on the impact of surgery because techniques vary greatly. A modified preservation of the so-called olfactory strip is described that utilizes a small nasoseptal flap and wide exposure. Methods A cohort of patients undergoing pituitary surgery and endoscopic sinonasal tumor surgery were assessed. Patient-reported outcomes (Sino-Nasal Outcome Test [SNOT22] and Nasal Symptom Score [NSS]) were recorded. A global score of sinonasal function and the impact on smell and taste were obtained. Objective smell discrimination testing was performed in the pituitary group with the Smell Identification Test. Outcomes were assessed at baseline and at 6 months. Results Ninety-eight patients, n = 40 pituitary (50.95 ± 15.31 years; 47.5% female) and n = 58 tumor (52.35 ± 18.51 years; 52.5% female) were assessed. For pituitary patients, NSSs were not significantly different pre- and postsurgery (2.75 ± 3.40 versus 3.05 ± 3.03; p = 0.53). SNOT22 scores improved postsurgery (1.02 ± 0.80 versus 0.83 ± 0.70; p = 0.046). Objective smell discrimination scores between baseline and 6 months were similar (31.63 ± 3.49 versus 31.35 ± 4.61; p = 0.68). No difference in change of olfaction was seen compared with controls (Kendall tau-b p = 0.46). Conclusions Preservation of the olfactory strip can provide a low morbidity approach without adversely affecting olfaction and maintaining reconstruction options.

Outside-In Frontal Drill-Out: How I Do It.

BACKGROUND: The Draf 3 frontal sinusotomy, or modified Lothrop procedure has been used to treat recalcitrant rhinosinusitis, frontal sinus mucocoeles or to provide access for cerebrospinal fluid leaks, frontoethmoid fractures, frontal sinus tumors and skull base tumors. OBJECTIVE: To describe authors approach to the "Outside-In Frontal Drill-Out". METHODS: Descriptive. RESULTS: The "Outside-In" frontal drill-out is an approach that emphasizes the early identification of the first olfactory neuron, maximization of bone removal, and preservation of the posterior table mucosa. CONCLUSION: The advantages of this approach are it provides unobstructed view and identifies anatomic limits early, bone removal is fast and efficient; it is safe, and it is a robust technique based upon fixed anatomic landmarks.

Costal Cartilage Lateral Crural Strut Graft vs Cephalic Crural Turn-in for Correction of External Valve Dysfunction.

IMPORTANCE: External nasal valve dysfunction (EVD) is a common cause of nasal obstruction. OBJECTIVE: To evaluate costal cartilage lateral crural strut grafts vs cephalic crural turn-in to support the weak lateral crus in patients with EVD. DESIGN, SETTING, AND PARTICIPANTS: In this prospective cohort study, patients with clinically diagnosed EVD were assessed at the Tertiary Rhinologic Center and underwent a costal cartilage underlay graft to the lateral crus or a cephalic turn-in cruralplasty. MAIN OUTCOMES AND MEASURES: Assessment of patient benefit was based on 22-Item Sinonasal Outcome Test (SNOT-22) and Nasal Obstruction Symptom Evaluation Scale (NOSE) scores. A Likert scale was also used to assess overall function and cosmesis. Objective assessment included postdecongestion nasal peak inspiratory flow, nasal airway resistance, and minimum cross-sectional area. RESULTS: Forty-one patients (mean [SD] 35.38 [12.73] years of age; 25 [61%] female) were assessed. Cephalic turn-in maneuver was used for 25 (61%) patients; costal cartilage lateral crural strut grafts, 16 (39%) patients. Costal cartilage grafts were used in patients undergoing revision but other baseline data were similar. Follow-up was mean 10.58 (7.52) months. All patients had significantly improved visual analog scale, SNOT-22, NOSE, patient-reported function, and cosmesis scores. The only objective test that improved was nasal peak inspiratory flow (114.76 [60.48] L/min vs 126.46 [61.17] L/min; P = .02). CONCLUSIONS AND RELEVANCE: Both techniques were effective in improving patient-reported outcomes and nasal peak inspiratory flow. Both are functionally and cosmetically viable options for correction of EVD. LEVEL OF EVIDENCE: 2.

How I Do It: Medial Flap Inferior Turbinoplasty.

INTRODUCTION: Techniques for inferior turbinate reduction vary from complete turbinectomy to limited cauterization. Surgical methods differ on the degree of tissue reduction and reliance on surgical tissue removal versus tissue ablation. METHOD: The technique and surgical steps of our preferred method of turbinate reduction are presented. RESULTS: Critical steps include proper design of the medial flap and removal of turbinate bone and lateral mucosa to allow lateral positioning of the medial flap. Bipolar cautery of the inferior turbinate artery branches allows complete haemostasis and undermining of the head allows proper debulking of the anterior aspect of the turbinate and widening of the nasal valve area. CONCLUSION: The medial flap inferior turbinoplasty provides consistent, robust results. Long-term relief of obstructive symptoms without additional risk of complication is expected with this procedure.

Sinonasal morbidity following tumour resection with and without nasoseptal flap reconstruction.

BACKGROUND: Sinonasal function can be affected by multiple treatment modalities but surgical techniques, such as the nasoseptal flap or Draf 3 procedure, have been implicated in poor post-treatment function. Prior studies have rarely used comparable populations and this study aims to assess the impact of surgical technique, mainly the nasoseptal flap, on sinonasal function in a group of comparable patients. METHODS: A prospective cohort of patients undergoing endoscopic surgery for sinonasal and skull base tumours was studied. Patients were analysed according to whether a nasoseptal flap was used. Other treatment factors included; use of the Draf 3, radiotherapy, removal of olfactory apparatus and dural resection. The Sinonasal Outcome Test 22 (SNOT22), a nasal symptom score (NSS), global function score and nasal obstruction scores were recorded pre and post treatment. RESULTS: One hundred and eighteen patients were assessed. Forty-two patients had a nasoseptal flap. Perioperative radiotherapy was higher in the nasoseptal group, as was dural resection and the need to remove the olfactory apparatus. Despite this, there was no significant difference in SNOT22 scores and NSS. Radiotherapy was detrimental to sinonasal function with SNOT22 and NSS. CONCLUSION: The use of a nasospetal flap in surgery does not affect patient quality of life and sinonasal function after endoscopic tumour resection. Pathology is a better predictor of morbidity, with loss of function from radiotherapy or resection of functional areas such as the olfactory apparatus having a greater impact.

Long-term outcomes in endoscopic dacryocystorhinostomy.

PURPOSE OF REVIEW: This study reviews the current body of literature with recent updates and briefly describes the powered endoscopic dacryocystorhinostomy (DCR) approach. RECENT FINDINGS: This review highlights recent studies including a meta-analysis of outcomes in DCR approaches, and compares each method to external DCR. When analyzed by method, endoscopic DCR with powered instrumentation success rates are comparable to the external approach, whereas the laser-assisted endoscopic DCR had a lower success rate. Additionally, several studies have demonstrated that long-term results in powered endoscopic DCR compare favorably with external approach in both primary and revision cases. SUMMARY: Endoscopic DCR with powered instrumentation is comparable to external DCR and also allows simultaneous adjunctive procedures while avoiding external scar. The powered endoscopic approach to DCR and methods to optimize success are described.

Advances in subcutaneous immunotherapy.

PURPOSE OF REVIEW: Current limitations in subcutaneous immunotherapy (SCIT) include the length of time required to achieve tolerance as well as the potential for systemic side-effects. Advances in allergen immunotherapy include targeted therapies to B-cell and T-cell pathways that can lead to more rapid desensitization and potentially the prevention of allergic disease. RECENT FINDINGS: Novel molecularly engineered compounds and delivery vehicles allow for rapid and efficient desensitization. Combination with immune modifiers, treatment with epitope-based compounds, and hypoallergenic recombinant vaccines have the potential to improve immunogenicity while limiting systemic side-effects. SUMMARY: Advances in SCIT create new therapeutic opportunities for patients to improve safety, efficacy, and compliance. Concepts using epitope-based immunotherapy and carrier-fusion peptides have the potential to induce tolerance quickly via selective B-cell and T-cell pathways.

Handheld micromanipulator for robot-assisted stapes footplate surgery.

Stapes footplate surgery is complex and delicate. This surgery is carried out in the middle ear to improve hearing. High accuracy is required to avoid critical tissues and structures near the surgical worksite. By suppressing the surgeon's tremor during the operation, accuracy can be improved. In this paper, a fully handheld active micromanipulator known as Micron is evaluated for its feasibility for this delicate operation. An ergonomic handle, a custom tip, and a brace attachment were designed for stapes footplate surgery and tested in a fenestration task through a fixed speculum. Accuracy was measured during simulated surgery in two different scenarios: Micron off (unaided) and Micron on (aided), both with image guidance. Preliminary results show that Micron significantly reduces the mean position error and the mean duration of time spent in specified dangerous zones.

Identification of genetic and chemical modulators of zebrafish mechanosensory hair cell death.

Inner ear sensory hair cell death is observed in the majority of hearing and balance disorders, affecting the health of more than 600 million people worldwide. While normal aging is the single greatest contributor, exposure to environmental toxins and therapeutic drugs such as aminoglycoside antibiotics and antineoplastic agents are significant contributors. Genetic variation contributes markedly to differences in normal disease progression during aging and in susceptibility to ototoxic agents. Using the lateral line system of larval zebrafish, we developed an in vivo drug toxicity interaction screen to uncover genetic modulators of antibiotic-induced hair cell death and to identify compounds that confer protection. We have identified 5 mutations that modulate aminoglycoside susceptibility. Further characterization and identification of one protective mutant, sentinel (snl), revealed a novel conserved vertebrate gene. A similar screen identified a new class of drug-like small molecules, benzothiophene carboxamides, that prevent aminoglycoside-induced hair cell death in zebrafish and in mammals. Testing for interaction with the sentinel mutation suggests that the gene and compounds may operate in different pathways. The combination of chemical screening with traditional genetic approaches is a new strategy for identifying drugs and drug targets to attenuate hearing and balance disorders.

Partial glucocorticoid agonist-like effects of imipramine on hypothalamic-pituitary-adrenocortical activity, thymus weight, and hippocampal glucocorticoid receptors in male C57BL/6 mice.

Abnormal hypothalamic-pituitary-adrenocortical (HPA) activity may provide clues to the neurochemistry of depression. Psychotic depression has one of the highest rates of elevated HPA activity and is most often responsive to the tricyclic class of antidepressants. Because successful treatment resolves HPA as well as psychiatric symptoms, we hypothesized, in light of evidence that tricyclic antidepressants can affect glucocorticoid receptor function, that these drugs would mimic glucocorticoid feedback inhibition of HPA activity. To test this hypothesis, we measured circadian nadir (morning) and peak (evening) as well as restraint stress-induced levels of plasma ACTH and corticosterone in adrenalectomized (ADX) and sham-ADX (Sham) male C57BL/6 mice after 8 wk of imipramine (20 mg/kg/d, ip) or saline treatment. Antidepressant efficacy was confirmed by decreased immobility in forced-swim testing. When glucocorticoids were low or absent, imipramine mimicked glucocorticoid action in inhibiting evening ACTH in ADX mice and tending to inhibit morning corticosterone in Shams. However, when glucocorticoid levels were high, imipramine appeared to interfere with feedback inhibition by increasing post-stress ACTH and tending to increase evening corticosterone in Sham mice. Imipramine also decreased thymus weight in ADX and increased thymus weight in Sham mice. Imipramine stimulated morning ACTH in ADX mice, possibly by mimicking facilitative effects of high glucocorticoids. Short-term imipramine treatment was capable of inducing nuclear translocation of hippocampal glucocorticoid receptors in ADX mice. We conclude that imipramine effects on glucocorticoid-sensitive endpoints in vivo resemble those of a glucocorticoid partial agonist.