miR-146a and miR-146b regulate the expression of ICAM-1 in giant cell arteritis.

Giant cell arteritis (GCA) is an inflammatory disease of large/medium-sized arteries. MiRNAs are small, non-coding RNAs that inhibit gene expression at post-transcriptional level. Several miRNAs have been shown to be dysregulated in temporal artery biopsies (TABs) from GCA patients, but their role is unknown. The aims of the present work were: to gain insight into the link between inflammation and miRNA up-regulation in GCA; to identify the role of miR-146a and miR-146b. Primary cultures from TABs were treated with IL-1ß, IL-6, soluble IL-6R (sIL6R), IL-17, IL-22, IFNγ, LPS and PolyIC. Correlations between cytokine mRNA and miRNA levels were determined in inflamed TABs. Primary cultures from TABs, human aortic endothelial and smooth muscle cells and ex-vivo TAB sections were transfected with synthetic miR-146a and miR-146b to mimic miRNA activities. Cell viability, target gene expression, cytokine levels in culture supernatants were assayed. Treatment of primary cultures from TABs with IL-1ß and IL-17 increased miR-146a expression while IL-1ß, IL-6+sIL6R and IFNγ increased miR-146b expression. IFNγ and IL-1ß mRNA levels correlated with miR-146a/b levels. Following transfection, cell viability decreased only in primary cultures from TABs. Moreover, transfection of miR-146a/b mimics increased ICAM-1 gene expression and production of the soluble form of ICAM-1 by primary cultures from TABs and by ex-vivo TABs. ICAM-1 expression was higher in inflamed than normal TABs and ICAM-1 levels correlated with miR-146a/b levels. Expression of miR-146a and miR-146b in GCA appeared to be driven by inflammatory cytokines (e.g. IL-1ß, IFNγ). miR-146a and miR-146b seem responsible for the increase of soluble ICAM-1.

Medullary Thyroid Carcinomas Classified According to the International Medullary Carcinoma Grading System and a Surveillance, Epidemiology, and End Results-Based Metastatic Risk Score: A Correlation With Genetic Profile and Angioinvasion.

Due to the lack of a standardized tool for risk-based stratification, the International Medullary Carcinoma Grading System (IMTCGS) has been proposed for medullary thyroid carcinomas (MTCs) based on necrosis, mitosis, and Ki67. Similarly, a risk stratification study using the Surveillance, Epidemiology, and End Results (SEER) database highlighted significant differences in MTCs in terms of clinical-pathological variables. We aimed to validate both the IMTCGS and SEER-based risk table on 66 MTC cases, with special attention to angioinvasion and the genetic profile. We found a significant association between the IMTCGS and survival because patients classified as high-grade had a lower event-free survival probability. Angioinvasion was also found to be significantly correlated with metastasis and death. Applying the SEER-based risk table, patients classified either as intermediate- or high-risk had a lower survival rate than low-risk patients. In addition, high-grade IMTCGS cases had a higher average SEER-based risk score than low-grade cases. Moreover, when we explored angioinvasion in correlation with the SEER-based risk table, patients with angioinvasion had a higher average SEER-based score than patients without angioinvasion. Deep sequencing analysis found that 10 out of 20 genes frequently mutated in MTCs belonged to a specific functional class, namely chromatin organization, and function, which may be responsible for the MTC heterogeneity. In addition, the genetic signature identified 3 main clusters; cases belonging to cluster II displayed a significantly higher number of mutations and higher tumor mutational burden, suggesting increased genetic instability, but cluster I was associated with the highest number of negative events. In conclusion, we confirmed the prognostic performance of the IMTCGS and SEER-based risk score, showing that patients classified as high-grade had a lower event-free survival probability. We also underline that angioinvasion has a significant prognostic role, which has not been incorporated in previous risk scores.

Dupilumab in the treatment of severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP): A multicentric observational Phase IV real-life study (DUPIREAL).

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with significant morbidity and reduced health-related quality of life. Findings from clinical trials have demonstrated the effectiveness of dupilumab in CRSwNP, although real-world evidence is still limited. METHODS: This Phase IV real-life, observational, multicenter study assessed the effectiveness and safety of dupilumab in patients with severe uncontrolled CRSwNP (n = 648) over the first year of treatment. We collected data at baseline and after 1, 3, 6, 9, and 12 months of follow-up. We focused on nasal polyps score (NPS), symptoms, and olfactory function. We stratified outcomes by comorbidities, previous surgery, and adherence to intranasal corticosteroids, and examined the success rates based on current guidelines, as well as potential predictors of response at each timepoint. RESULTS: We observed a significant decrease in NPS from a median value of 6 (IQR 5-6) at baseline to 1.0 (IQR 0.0-2.0) at 12 months (p < .001), and a significant decrease in Sino-Nasal Outcomes Test-22 (SNOT-22) from a median score of 58 (IQR 49-70) at baseline to 11 (IQR 6-21; p < .001) at 12 months. Sniffin' Sticks scores showed a significant increase over 12 months (p < .001) compared to baseline. The results were unaffected by concomitant diseases, number of previous surgeries, and adherence to topical steroids, except for minor differences in rapidity of action. An excellent-moderate response was observed in 96.9% of patients at 12 months based on EPOS 2020 criteria. CONCLUSIONS: Our findings from this large-scale real-life study support the effectiveness of dupilumab as an add-on therapy in patients with severe uncontrolled CRSwNP in reducing polyp size and improving the quality of life, severity of symptoms, nasal congestion, and smell.

Is it possible to diagnose Posterior Semicircular Canal BPPV from the sitting position? The role of the Head Pitch Test and the upright tests along the RALP and LARP planes.

PURPOSE: The diagnosis of benign paroxysmal positional vertigo (BPPV) involving the posterior semicircular canal (PSC) is traditionally entrusted to positioning tests where patients are rapidly brought in the supine position. This prospective study aims to define the role of a diagnostic protocol for PSC-BPPV including only upright tests. MATERIALS AND METHODS: 109 patients with PSC-BPPV were enrolled. The Head Pitch Test (HPT) was carried out first. If uneventful, the patient's head was turned 45° to each side and bent back-and-forth along the plane aligning either with the right anterior-left posterior (RALP) or left anterior-right posterior (LARP) canals, thus performing the upright RALP / upright LARP (uRALP/uLARP) test. Nystagmus observed was used to predict the diagnosis, which was therefore confirmed by Dix-Hallpike tests. RESULTS: PSC-BPPV could be correctly diagnosed in 75.2% of cases with the sole HPT and in 87.2% of cases by adding the uRALP/uLARP test (Upright Protocol). The time elapsed from symptoms onset was closely related to the protocol sensitivity, as it reached 100% (64/64) in acute patients while decreased to 68.9% (31/45) in cases evaluated after 7 days (p < 0.001). CONCLUSIONS: Upright maneuvers could correctly diagnose PSC-BPPV in most cases. uRALP/uLARP test demonstrated to improve the sensitivity of the HPT, mainly in recent-onset BPPV.

Reduction in healthcare services during the COVID-19 pandemic: Patient screening based on symptoms is an effective strategy for avoiding delayed laryngeal cancer diagnosis.

OBJECTIVE: Restriction in healthcare services during the COVID-19 pandemic caused delays in the diagnosis and treatment of several diseases. To overcome the risk of missed diagnosis of head and neck cancers, before deleting the scheduled appointments, we have introduced a selection of the patients by examining the clinical presenting issue and previous medical history. The aim of this study is to show the effects of the abovementioned strategy on the diagnosis and management of laryngeal cancer. METHODS: Data were extracted from the Hospital software regarding the new diagnosis of laryngeal SCC in the periods from March 2020 to December 2020 during the pandemic (study group) and from March 2019 to December 2019 (control group) were collected. Data were compared regarding: TNM stage, time from first medical examination to histological diagnosis (Time-1), and time form histological diagnosis to beginning of treatments (Time-2). RESULTS: The final study group was composed by 19 laryngeal cancers, the control group by 25 cases. No significant differences were found in the tumour stage between the groups. In the study group, Time-1 was shorter (24 days versus 43 days, p = 0.012), while Time-2 in surgically-treated patients was longer (20 days versus 9 days, p = 0.012). CONCLUSION: During the pandemic, there was a dramatic lack of medical and nurse staff needed for surgical procedures. As consequence, the time between the diagnosis of malignancy and surgical treatment increased. In our unit, an efficient patient selection strategy to reschedule medical appointments avoided a dangerous shift toward higher laryngeal cancer stages.

Pneumolabyrinth: a systematic review.

PURPOSE: The aim of this study is to provide a systematic review of the literature about the etiology, clinical and radiological presentation, surgical management, and outcomes of pneumolabyrinth (PNL). METHODS: A systematic review of the literature was performed including studies published up to September 2020 in electronic databases (PubMed/MEDLINE, EMBASE, Cochrane Library, and Scopus). The PRISMA standard was applied to identify English, Italian, or French-language studies mentioning PNL. Full texts lacking information on the etiology were excluded. Data concerning the cause, site of air bubbles/fistula, clinical presentation, treatment, and outcome were collected. A qualitative synthesis of the results was performed. RESULTS: Seventy-eight articles were eventually included; 132 patients were involved in the qualitative synthesis. The most common causes were: stapes surgery (24/132, 18.2%), temporal bone fracture (42/132, 31.8%), head trauma without temporal bone fracture (19/132, 14.4%), penetrating trauma (21/132, 15.9%), and barotrauma (15/132, 11.4%). The site most commonly involved was the vestibule (102/107, 95.3%), followed by cochlea (43/107, 40.2%) and semicircular canals (25/107, 23.4%). CONCLUSION: The etiopathogenesis of PNL can be summarized in traumatic, iatrogenic, or inflammatory/infective. Its management consists in exploratory tympanotomy and sealing the fistula, but also conservative treatments can be attempted. Vestibular symptoms disappear in the majority of cases. Instead, the prognosis of hearing function is widely variable, and complete recovery is less probable. The certainty of evidence is still too low to make it useful for clinical decision-making.

The effect of superior canal dehiscence size and location on audiometric measurements, vestibular-evoked myogenic potentials and video-head impulse testing.

PURPOSE: To correlate objective measures of audio-vestibular function with superior canal dehiscence (SCD) size and location in ears with SCD and compare results with literature. METHODS: We retrospectively evaluated 242 patients exhibiting SCD and/or extremely thinned bone overlying superior canals (SC) on CT scans and selected 73 SCD patients (95 ears with SCD). Data concerning audiometry, impedance audiometry, video-head impulse test (vHIT), cervical vestibular-evoked myogenic potentials (cVEMPs) and ocular VEMPs (oVEMPs) to air- (AC) and bone-conducted (BC) stimuli were collected for each pathologic ear and correlated with dehiscence size and location. RESULTS: AC pure-tone average (PTA) (p = 0.013), low-frequency air-bone gap (ABG) (p < 0.001), AC cVEMPs amplitude (p = 0.002), BC cVEMPs amplitude (p < 0.001) and both AC and BC oVEMPs amplitude (p < 0.001) positively correlated with increasing SCD size. An inverse relationship between dehiscence length and both AC cVEMPs and oVEMPs thresholds (p < 0.001) and SC vestibulo-ocular reflex (VOR) gain (p < 0.001) was observed. Dehiscences at the arcuate eminence (AE) exhibited lower SC VOR gains compared to SCD along the ampullary arm (p = 0.008) and less impaired BC thresholds than dehiscences at the superior petrosal sinus (p = 0.04). CONCLUSION: We confirmed that SCD size affects AC PTA, ABG and both amplitudes and thresholds of cVEMPs and oVEMPs. We also described a tendency for SC function to impair with increasing SCD size and when dehiscence is located at the AE. The latter data may be explained either by a spontaneous canal plugging exerted by middle fossa dura or by a dissipation through the dehiscence of mechanical energy conveyed to the endolymph during high-frequency impulses.

Safe tracheotomy for patients with COVID-19.

Patients affected by severe acute respiratory syndrome coronavirus 2 disease (COVID-19) with respiratory distress may need invasive mechanical ventilation for a long period of time. Head and neck surgeons are becoming increasingly involved in the care of COVID-19 patients because of the rapidly increasing number of tracheotomies required. This procedure, when performed without protection, may lead to the infection of the medical and nursing staff caring for the patient. The aim of this report is to share our protocol for performing a safe surgical tracheotomy in COVID-19 patients. Infection of the nursing/medical staff involved in the first 30 tracheotomies performed in patients affected by COVID-19 in the Intensive Care Unit of a tertiary referral center were evaluated. Mistakes that occurred during surgery were analyzed and discussed. None of the nursing/medical staff presented signs or symptoms of COVID-19 within 15 days after the procedure. Conclusion: The authors have prepared a protocol for performing a safe surgical tracheotomy in patients affected by COVID-19. Surgeons who might be involved in performing the tracheotomies should become familiar with these guidelines.

Cochlear function after type-1 tympanoplasty: endoscopic versus microscopic approach, a comparative study.

PURPOSE: To investigate and compare the effect of endoscopic and microscopic type 1 tympanoplasty on the cochlear function, to determine if they have a different impact on the inner ear function. METHODS: 72 ears treated by transcanal endoscopic type 1 tympanoplasty and 84 ears treated by microscopic type 1 tympanoplasty in 3 tertiary referral centers were enrolled in the study. Microscopic type 1 tympanoplasty were performed by transcanal or retroauricular approach. Only patients with mobile and intact ossicular chain were involved in the study. A retrospective chart review was performed. Main outcome measures were: (1) change in bone conduction thresholds at 250, 500, 1000, 2000, 4000 Hz; (2) change in bone conduction Pure Tone Audiometry; (3) correlation of audiometric outcomes with surgical technique, graft type and graft position. RESULTS: A mild postoperative bone conduction threshold shift was observed at 2000 Hz and 4000 Hz in both groups, without significant differences between the two groups. No statistically significant modifications in bone conduction were observed at any frequencies in patients operated by transcanal endoscopic approach compared with those who underwent transcanal or retroauricular microscopic type 1 tympanoplasty. Moreover, neither the placement nor the type of the graft seemed to influence the cochlear function preservation. CONCLUSIONS: The endoscopic and the microscopic approaches have a similar impact on the bone conduction threshold during type 1 tympanoplasty. In particular, the one-handed manipulation of the ossicular chain during the endoscopic technique did not show an increased risk of inner ear damage.

Isolated horizontal canal hypofunction differentiating a canalith jam from an acute peripheral vestibular loss.

OBJECTIVES: To describe a unique case of acute vertigo presenting with spontaneous horizontal nystagmus (SHN) and a clinical picture consistent with right acute peripheral vestibular loss (APVL) in which an isolated hypofunction of a horizontal semicircular canal (HSC) permitted to detect a spontaneous canalith jam and treat the patient accordingly. METHODS: Case report and literature review. RESULTS: A 74-year old woman presented with acute vertigo, left-beating SHN and a clinical picture consistent with right APVL. Nevertheless, vestibular evoked myogenic potentials were normal with symmetrical amplitudes and the video head impulse test (vHIT) revealed an isolated hypofunction of the right HSC. After repeated head shakings, the supine roll test evoked bilaterally a positioning paroxysmal geotropic horizontal nystagmus suggesting benign paroxysmal positional vertigo involving the non-ampullated arm of the right HSC. vHIT and caloric testing confirmed restitution of HSC function after repositioning maneuvers. CONCLUSIONS: In case of acute vertigo with SHN, a complete functional assessment of vestibular receptors and afferents should always be given in order to avoid misdiagnosis. Canalith jam should be considered in case of spontaneous nystagmus and isolated canal hypofunction.

Audiovestibular Findings in Patients with Concurrent Superior Canal Dehiscence and Vestibular Schwannoma.

OBJECTIVE: To describe the clinical-instrumental findings in case of concurrent superior canal dehiscence (SCD) and ipsilateral vestibular schwannoma (VS), aiming to highlight the importance of an extensive instrumental assessment to achieve a correct diagnosis. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Five patients with concurrent SCD and VS. INTERVENTION: Clinical-instrumental assessment and imaging. MAIN OUTCOME MEASURE: Clinical presentation, audiovestibular findings, and imaging. RESULTS: The chief complaints were hearing loss (HL) and unsteadiness (80%). Other main symptoms included tinnitus (60%) and pressure-induced vertigo (40%). Mixed-HL was identified in three patients and pure sensorineural-HL in 1, including a roll-over curve in speech-audiometry in two cases. Vibration-induced nystagmus was elicited in all cases, whereas vestibular-evoked myogenic potentials showed reduced thresholds and enhanced amplitudes on the affected side in three patients. Ipsilesional weakness on caloric testing was detected in three patients and a bilateral hyporeflexia in one. A global canal impairment was detected by the video-head impulse test in one case, whereas the rest of the cohort exhibited a reduced function for the affected superior canal, together with ipsilateral posterior canal impairment in two cases. All patients performed both temporal bones HRCT scan and brain-MRI showing unilateral SCD and ipsilateral VS, respectively. All patients were submitted to a wait-and-scan approach, requiring VS removal only in one case. CONCLUSION: Simultaneous SCD and VS might result in subtle clinical presentation with puzzling lesion patterns. When unclear symptoms and signs occur, a complete audiovestibular assessment plays a key role to address imaging and diagnosis.

Influence of Prior Endoscopic Sinus Surgery Extent on Dupilumab Effectiveness in CRSwNP Patients.

BACKGROUND: Guidelines recommend that the vast majority of patients with severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) should have at least one endoscopic sinus surgery (ESS) prior to starting biologics. Because ESS can be performed with a variable extension, the aim of this study would be to evaluate the association between surgical extensiveness, as measured by ACCESS score, and outcomes collected in patients treated with Dupilumab. MATERIALS AND METHODS: This is a multicentric retrospective study; patients affected by CRSwNP who were subjected to Dupilumab therapy and who underwent at least one ESS prior to Dupilumab initiation were included. ACCESS score was assigned to each patient's pre-Dupilumab CT scan. Subjective and objective parameters (SNOT-22, NPS, VAS scores, Sniffin' Sticks) were collected before and during the administration of therapy. Statistical correlations between ACCESS scores and clinical outcomes were investigated. RESULTS: A total of 145 patients were included; mean time from last previous ESS was 68.6 months, and on average, patients were subjected to 2.2 surgeries. Many correlations with ACCESS scores were demonstrated: better NPS at all timepoints and subjective scores (30-days SNOT-22, VAS nasal obstruction, and rhinorrhea) were achieved in patients with low ACCESS score (more extensive ESS). On the other hand, significantly worse VAS loss of smell values were demonstrated in patients with lower ACCESS scores. CONCLUSION: Dupilumab patients subjected to a prior extensive ESS may have reduced size of polyps and improved subjective indicators, together with a decreased chance to recover smell, when compared with patients who underwent a minimal excision. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:1556-1563, 2024.

Vestibular Hypofunction in ARSACS Syndrome: A Possible Pitfall in the Differential Diagnosis of Recessive Cerebellar and Afferent Ataxias.

Objectives: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset ataxia characterized by cerebellar dysfunction, spasticity, and sensory-motor polyneuropathy due to variations in the SACS gene (13q11). To date, no studies have instrumentally assessed vestibular function in this condition. Methods: We report a 36-year-old woman with diagnosis of ARSACS syndrome due to homozygous mutation (c.12232 C>T, p.Arg4078Ter) in the SACS gene. Neurologic examination showed spastic-ataxic gait, dysarthric speech, 4-limb ataxia, and spastic hypertonia with lower limb hyperreflexia. Results: A vestibular instrumental evaluation including bedside oculomotor testing found gaze-evoked and rebound nystagmus on horizontal and vertical gaze, saccadic movements within normality ranges, saccadic pursuit, and slightly impaired visually enhanced vestibulo-ocular reflex (VVOR). A near-normal VOR suppression (VORS) was recorded. Neither head shakings, skull vibrations, nor supine positionings could evoke nystagmus. Finally, the video-head impulse test detected a symmetrical VOR impairment for all the semicircular canals (SCs), mostly involving the horizontal SCs, with corrective saccades in all planes. Discussion: Vestibular hypofunction may be found in ARSACS syndrome and may represent a possible pitfall in the differential diagnosis of recessive cerebellar and afferent ataxias. In this setting, ARSACS syndrome should be considered in the differential diagnosis of CANVAS.

Posterior Semicircular Canal Dehiscence with Vestibulo-Ocular Reflex Reduction for the Affected Canal at the Video-Head Impulse Test: Considerations to Pathomechanisms.

Posterior semicircular canal dehiscence (PSCD) has been demonstrated to result in a third mobile window mechanism (TMWM) in the inner ear similar to superior semicircular canal dehiscence (SSCD). Typical clinical and instrumental features of TMWM, including low-frequency conductive hearing loss (CHL), autophony, pulsatile tinnitus, sound/pressure-induced vertigo and enhanced vestibular-evoked myogenic potentials, have been widely described in cases with PSCD. Nevertheless, video-head impulse test (vHIT) results have been poorly investigated. Here, we present six patients with PSCD presenting with a clinical scenario consistent with a TMWM and an impaired vestibulo-ocular reflex (VOR) for the affected canal on vHIT. In two cases, an additional dehiscence between the facial nerve and the horizontal semicircular canal (HSC) was detected, leading to a concurrent VOR impairment for the HSC. While in SSCD, a VOR gain reduction could be ascribed to a spontaneous "auto-plugging" process due to a dural prolapse into the canal, the same pathomechanism is difficult to conceive in PSCD due to a different anatomical position, making a dural herniation less likely. Alternative putative pathomechanisms are discussed, including an endolymphatic flow dissipation during head impulses as already hypothesized in SSCD. The association of symptoms/signs consistent with TMWM and a reduced VOR gain for the posterior canal might address the diagnosis toward PSCD.

Surgical margins in head and neck squamous cell carcinoma: what is 'close'?

The aim of this systematic review is to evaluate the definition of close margin in head and neck squamous cell carcinoma (HNSCC), and its possible prognostic significance. An appropriate string was run on PubMed to retrieve articles discussing the 'close' surgical margin issue in HNSCC. A double cross-check was performed on citations and full-text articles retrieved. In total, 348 articles were identified. Further references were included by using the option "Titles in your search terms" option in PubMed. 15 papers were finally included for qualitative synthesis. In vocal cord surgery of HNSCC, a close margin could be considered to be ≤1 mm, in the larynx ≤5 mm, in the oral cavity ≤4 mm, and in the oropharynx ≤5 mm. In each patient, the choice of extent of close margin should be balanced against general condition, tumor stage, and functional issues to indicate appropriate adjuvant therapy.

Low-Frequency Air-Bone Gap and Pulsatile Tinnitus Due to a Dural Arteriovenous Fistula: Considerations upon Possible Pathomechanisms and Literature Review.

Low-frequency air-bone gap (ABG) associated with pulsatile tinnitus (PT) and normal impedance audiometry represents a common finding in patients with third window syndromes. Other inner disorders, including Meniere's disease (MD), perilymphatic fistula and intralabyrinthine schwannoma, might sometimes result in a similar scenario. On the other hand, PT is frequently associated with dural arteriovenous fistula (DAVF), while conductive hearing loss (CHL) is extremely rare in this clinical setting. A 47-year-old patient was referred to our center with progressive left-sided PT alongside ipsilateral fullness and hearing loss. She also experienced headache and dizziness. Otoscopy and video-oculographic examination were unremarkable. Conversely, a detailed instrumental audio-vestibular assessment revealed low-frequency CHL with normal impedance audiometry, slight left-sided caloric weakness, slightly impaired vestibular-evoked myogenic potentials on the left and normal results on the video-head impulse test, consistent with an MD-like instrumental profile. Gadolinium-enhanced brain MRI revealed an early enhancement of the left transverse sinus, consistent with a left DAVF between the left occipital artery and the transverse sinus, which was then confirmed by angiography. A trans-arterial embolization with Onyx glue was performed, resulting in a complete recession of the symptoms. Post-operatively, the low-frequency ABG disappeared, supporting the possible role of venous intracranial hypertension and abnormal pressure of inner ear fluids in the onset of symptoms and offering new insights into the pathomechanism of inner ear CHL.

Impaired Vestibulo-Ocular Reflex on Video Head Impulse Test in Superior Canal Dehiscence: "Spontaneous Plugging" or Endolymphatic Flow Dissipation?

Surgical plugging of the superior semicircular canal (SSC) represents an effective procedure to treat disabling symptoms in superior canal dehiscence (SCD), despite resulting in an impaired vestibulo-ocular reflex (VOR) gain for the SSC. On the other hand, SSC hypofunction on video head impulse test (vHIT) represents a common finding in patients with SCD exhibiting sound/pressure-induced vertigo, a low-frequency air-bone gap (ABG), and enhanced vestibular-evoked myogenic potentials (VEMPs). "Spontaneous canal plugging" has been assumed as the underlying process. Nevertheless, missing/mitigated symptoms and/or near-normal instrumental findings would be expected. An endolymphatic flow dissipation has been recently proposed as an alternative pathomechanism for SSC VOR gain reduction in SCD. We aimed to shed light on this debate by comparing instrumental findings from 46 ears of 44 patients with SCD exhibiting SSC hypofunction with post-operative data from 10 ears of 10 patients with SCD who underwent surgical plugging. While no difference in SSC VOR gain values was found between the two groups (p = 0.199), operated ears developed a posterior canal hypofunction (p = 0.002). Moreover, both ABG values (p = 0.012) and cervical/ocular VEMP amplitudes (p < 0.001) were significantly higher and VEMP thresholds were significantly lower (p < 0.001) in ears with SCD compared to operated ears. According to our data, canal VOR gain reduction in SCD should be considered as an additional sign of a third window mechanism, likely due to an endolymphatic flow dissipation.

Vestibular assessment in sudden sensorineural hearing loss: Role in the prediction of hearing outcome and in the early detection of vascular and hydropic pathomechanisms.

Introduction: Predicting hearing outcome in sudden sensorineural hearing loss (SSNHL) is challenging, as well as detecting the underlying pathomechanisms. SSNHL could be associated with vestibular damage since cochleo-vestibular structures share the same vascularization, along with being in close anatomical proximity. Whereas viral inflammations and autoimmune/vascular disorders most likely represent the involved aetiologies, early-stage Menière's disease (MD) can also present with SSNHL. Since an early treatment could beneficially influence hearing outcome, understanding the possible etiology plays a pivotal role in orienting the most appropriate treatment. We aimed to evaluate the extent of vestibular damage in patients presenting with SSNHL with or without vertigo, investigate the prognostic role of vestibular dysfunctions on hearing recovery and detect specific lesion patterns related to the underlying pathomechanisms. Methods: We prospectively evaluated 86 patients with SSNHL. Audio-vestibular investigation included pure-tone/speech/impedance audiometry, cervical/ocular-VEMPs, vHIT and video-Frenzel examination. White matter lesions (WML) were evaluated on brain-MRI. Patients were followed-up and divided into "SSNHL-no-vertigo," "SSNHL+vertigo" and "MD" subgroups. Results: Hearing was more impaired in "SSNHL+vertigo" patients who exhibited either down-sloping or flat-type audiograms, and was less impaired in "MD" where low frequencies were mostly impaired (p < 0.001). Otolith receptors were more frequently involved than semicircular canals (SCs). Although the "SSNHL-no-vertigo" subgroup exhibited the lowest vestibular impairment (p < 0.001), 52% of patients developed otolith dysfunctions and 72% developed nystagmus. Only "MD" subjects showed anterior SC impairment and upbeating spontaneous/positional nystagmus. They more frequently exhibited cervical-VEMPs frequency tuning (p = 0.036) and ipsilesional spontaneous nystagmus (p < 0.001). "SSNHL+vertigo" subjects presented with more frequently impaired cervical-VEMPs and posterior SC and with higher number of impaired receptors (p < 0.001). They mainly exhibited contralesional spontaneous and vibration-induced nystagmus (p < 0.05) and only they showed the highest WML score and "vascular" lesion patterns (p < 0.001). Concerning the outcomes, hearing was better in "MD" and worse in "SSNHL+vertigo" (p < 0.001). Hearing recovery was mostly affected by cervical-VEMPs impairment and the number of involved receptors (p < 0.05). Patients with "vascular" lesion patterns presented with the highest HL degree and WML score (p ≤ 0.001), while none of them exhibited a complete hearing recovery (p = 0.026). Conclusions: Our data suggest that vestibular evaluation in SSNHL can provide useful information on hearing recovery and underlying aetiologies.