Place of Tubomanometry in Patulous Eustachian Tube Diagnosis.

OBJECTIVE: The aim of our study was to describe the diagnostic performances of tubomanometry (TMM) and to determine tubomanometric parameter thresholds for the diagnosis of patulous eustachian tube (PET). STUDY DESIGN: We performed a retrospective, monocentric study, including patients treated for PET vs control group. SETTING: This study was performed at the Otolaryngology Department of a tertiary-care hospital in the south of France. METHODS: We collected epidemiologic and clinical data, as well as adjusted opening latency index ("R"-index), rhinopharyngeal pressure threshold of tubal opening (Po), and velar contraction index (IVC) on TMM. Receiver operating characteristic (ROC) curves were used for determination of R index and Po thresholds. RESULTS: Twenty-one patients (26 patulous ears) and 14 controls (24 normal ears) were included. The R index values and Po values were significantly lower in the PET group vs controls (0.46 vs 0.80, respectively; P < .05 for R index and 13.89 vs 26.42 mbar, respectively; P < .05 for Po). No significant difference was reported between the 2 groups on IVC measurement (P = .784). After ROC curve analysis, R index was the most discriminating factor to classify PET patients with 89% specificity and 76% sensitivity with a threshold ≤0.6. Po value ≤10 mbar could support this diagnosis with more than 83% specificity. CONCLUSION: TMM is a reliable noninvasive method for positive diagnosis of PET. TMM could provide an accurate positive PET diagnosis and an objective evaluation for PET management.

Quantitative biomarkers allow the diagnosis of head and neck paraganglioma on multiparametric MRI.

PURPOSE: The aim of this study is to identify quantitative MR biomarkers in head and neck paragangliomas. METHODS: The study was approved by an institutional review board. A retrospective review of patients with head and neck paragangliomas (HNPGL) evaluated by time-resolved MRA sequences between 2009 and 2019 was performed. A control group investigated during the same period was analyzed, including nerve sheath tumors and metastatic lymph nodes from squamous cell carcinomas or undifferentiated nasopharyngeal cancer (UCNT). A gold standard was obtained for all cases. Semi-quantitative parameters of enhancement were extracted from time-intensity curves on time-resolved MRA sequences and diffusion weighted imaging/DWI was assessed for each lesion. RESULTS: Sixty head and neck paragangliomas (HNPGLs) were included from 50 patients. The control group consisted of 30 parapharyngeal space lesions (27 patients), which included nerve sheath tumors (n = 12) and metastatic lymph nodes (n = 18) from squamous cell carcinomas or UCNT. PGLs showed a shorter time-to-peak value compared to other groups, measured at 25.0 +/- 29 sec. The wash-in and wash-out ratios were also significantly higher for PGLs, respectively measured at 5.34 ± 2.99 (p < 0,001) and 1.24 ± 0.80 (p < 0.001). On DWI sequences, the mean ADC value for PGLs (1.17 ± 0.19 10^-3 mm2/s) was significantly different than the other tumor groups (p < 0.001). HNPGLs were clearly distinguishable from other tumors on classification with regression tree based on TTP and ADC values. These distinct group features were also consistent on principal component analysis. CONCLUSION: Our study identifies a multiparametric signature for disease subtyping, providing a strong impetus for switching from qualitative to quantitative analysis of deep soft-tissue tumors of the neck.

Syngeneic Transplantation of Rat Olfactory Stem Cells in a Vein Conduit Improves Facial Movements and Reduces Synkinesis after Facial Nerve Injury.

BACKGROUND: Posttraumatic facial paralysis is a disabling condition. Current surgical management by faciofacial nerve suture provides limited recovery. To improve the outcome, the authors evaluated an add-on strategy based on a syngeneic transplantation of nasal olfactory stem cells in a rat model of facial nerve injury. The main readouts of the study were the recording of whisking function and buccal synkinesis. METHODS: Sixty rats were allocated to three groups. Animals with a 2-mm facial nerve loss were repaired with a femoral vein, filled or not with olfactory stem cells. These two groups were compared to similarly injured rats but with a faciofacial nerve suture. Olfactory stem cells were purified from rat olfactory mucosa. Three months after surgery, facial motor performance was evaluated using video-based motion analysis and electromyography. Synkinesis was assessed by electromyography, using measure of buccal involuntary movements during blink reflex, and double retrograde labeling of regenerating motoneurons. RESULTS: The authors' study reveals that olfactory stem cell transplantation induces functional recovery in comparison to nontransplanted and faciofacial nerve suture groups. They significantly increase (1) maximal amplitude of vibrissae protraction and retraction cycles and (2) angular velocity during protraction of vibrissae. They also reduce buccal synkinesis, according to the two techniques used. However, olfactory stem cell transplantation did not improve axonal regrowth of the facial nerve, 3 months after surgery. CONCLUSIONS: The authors show here that the adjuvant strategy of syngeneic transplantation of olfactory stem cells improves functional recovery. These promising results open the way for a phase I clinical trial based on the autologous engraftment of olfactory stem cells in patients with a facial nerve paralysis.

Facial Nerve Canal Paraganglioma.

We report the case of a 72-year-old woman presenting with a progressive left peripheral facial paralysis and a facial canal mass extending through the stylomastoid foramen along the posterior edge of the parotid gland. On MRI, the early and intense enhancement was highly suggestive of paraganglioma but could not rule out a nonossifying hemangioma. Laboratory analysis showed normal plasma metanephrines. On F-FDOPA PET/CT, the mass exhibited a typical paraganglioma feature with a marked tumor uptake. Our case demonstrates that F-FDOPA plays a vital role in this rare entity and can avoid any further confirmatory invasive procedure.

Does NF2 status impact the results of combined surgery and adjunctive Gamma Knife surgery for large vestibular schwannomas?

In order to verify whether neurofibromatosis type 2 (NF2) could influence the oncological and functional outcome in large vestibular schwannoma (VS) surgery, we compared a group of NF2 patients operated with a facial nerve-sparing technique to a group of sporadic VSs of similar volume that underwent the same treatment regimen in the same period. Single-center retrospective cohort study about 12 consecutive NF2 and 69 non-NF2 patients operated on for large VS between September 2006 and November 2016. After resection, patients were allocated to an upfront Gamma Knife surgery policy of the tumor residue. At last follow-up examination, the facial nerve function was good (House-Brackmann grades I or II) in 92% of the NF2 and 83% of the non-NF2 patients (p = .90). The median volume of tumor residue was .92 cc in the NF2 group and .54 cc in the non-NF2 group (p = .14). Tumor control was achieved in 83% and 81% of cases in the NF2 and the non-NF2 populations, respectively, with a mean follow-up of 73 months in both groups. The 1-, 5-, and 7-year progression-free survival were 92%, 83%, and 83% respectively in the NF2 group, and 99%, 83%, and 80% in the non-NF2 group (p = .96). Our analysis of 12 NF2 and 69 non-NF2 patients operated on by the same surgical team with the same treatment regimen did not show any functional or tumor control difference between those groups.

Incidental Effect of Long-Term Tacrolimus Treatment on Sporadic Vestibular Schwannoma Volume Shrinkage and Clinical Improvement.

OBJECTIVE: We describe the effect of long-term tacrolimus delivery on sporadic vestibular schwannoma (VS). PATIENT: A 48-year-old woman who was diagnosed a right VS. INTERVENTION: Long-term tacrolimus delivery following liver transplant. MAIN OUTCOME MEASURES: Clinical examination, audiometric test, and gadolinium-contrasted magnetic resonance imaging. RESULTS: During the reported follow-up period, the patient felt hearing improvement especially in noisy environment. This was consistent with a clear audiometric improvement. Over a 26 months follow-up period, we noticed a 50% volume regression and a 40% decrease in the intensity of enhancement of the tumor after gadolinium injection. CONCLUSION: Tacrolimus, an immunosuppressant used to prevent rejection in organ transplant, could lead to VS volume shrinkage and hearing improvement. Tacrolimus could be an interesting new therapeutic weapon, especially for VS in Neurofibromatosis type 2.

Exploring the link between tumour metabolism and succinate dehydrogenase deficiency: A 18 F-FDOPA PET/CT study in head and neck paragangliomas.

OBJECTIVES: Nuclear imaging findings by virtue of phenotyping disease heavily depend on genetic background, metabolites, cell membrane specific targets and signalling pathways. PPGL related to succinate dehydrogenase subunits mutations (SDHx mutations) are less differentiated than other subgroups and therefore may lack to concentrate 18 F-FDOPA, a precursor of catecholamines biosynthesis. However, this 18 F-FDOPA negative phenotype has been reported mostly in SDHx-PPGL of sympathetic origin, suggesting that both genotype status and location (from sympathetic vs parasympathetic paraganglia; adrenal vs extra-adrenal) could influence 18 F-FDOPA uptake. The aim of this study was to test if SDHx drives 18 F-FDOPA uptake in presence of normal epinephrine/norepinephrine concentrations. DESIGN: Retrospective study PATIENTS: A cohort of 86 head and neck PPGL patients (including three metastatic) with normal metanephrines underwent 18 F-FDOPA PET/CT. The relationships between 18 F-FDOPA uptake and tumour genotype were evaluated. RESULTS: In nonmetastatic HNPGL (50 non-SDHx/33 SDHx), no significant difference was observed between these two groups for SUVmax (P = .256), SUVmean (P = .188), MTV 42% (P = .596) and total lesion uptake (P = .144). Metastatic HNPGL also had high elevated uptake values. CONCLUSIONS: Our results suggest that SDH deficiency or metastatic behaviour have no influence on 18 F-FDOPA uptake in HNPGL probably due to their very-well differentiation status, even at metastatic stage. The potential prognosticator value of 18 F-FDOPA uptake would need to be further explored in the setting of metastatic PPGL of sympathetic origin.

Predictive Factors of Early Postoperative and Long-Term Facial Nerve Function After Large Vestibular Schwannoma Surgery.

OBJECTIVE: The preservation of acceptable facial nerve (FN) function after surgery is the key concern for most patients with vestibular schwannomas (VS). To assess predictive factors of early postoperative and long-term FN function in patients harboring large VS operated with a FN-sparing technique. METHODS: Single-center retrospective cohort study with 169 consecutive large VS operated on between January 2003 and May 2015. Clinical, radiologic, and intraoperative factors were assessed according to FN function. RESULTS: At last follow-up examination, among the 145 patients without preoperative FN palsy, FN function was good (House-Brackmann [HB] grades I or II) in 84% and moderate (HB grade III) in 15% of patients. Only 1 patient presented with poor HB grade IV function. Multivariate logistic regression model showed the mean preoperative VS extrameatal diameter as being an independent predictor of an unfavorable initial FN outcome (odds ratio [OR], 1.062; P = 0.038). Surgical anatomic preservation of the cochlear nerve was associated with better FN outcomes (OR, 0.237; P = 0.012). A history of previous surgery seemed to be related to long-term impaired FN function (OR, 71.405; P = 0.042), as well as early postoperative FN function (OR, 19.068; P = 0.000). No correlation was found between a history of previous Gamma Knife surgery treatment (P = 0.225) or the extent of resection (P = 0.438) and impaired FN outcomes. History of previous surgery was identified as an unfavorable predictive recovery factor of impaired postoperative FN function (P = 0.034). CONCLUSIONS: As long as the extent of resection or additional Gamma Knife surgery have not been identified as predictive risk factors of postoperative FN palsy, we suggest that optimal resection is the main option for patients harboring large VS.

Malignant Aspergillus flavus Otitis Externa with Jugular Thrombosis.

We report a case of malignant otitis externa with jugular vein thrombosis caused by Aspergillus flavus. Magnetic resonance imaging revealed an unusual ink smudge pattern deep in a cervical abscess. The pattern was consistent with mycetoma and may be important for diagnosing these life-threatening infections.

Validation of French versions of the Facial Disability Index and the Facial Clinimetric Evaluation Scale, specific quality of life scales for peripheral facial palsy patients.

OBJECTIVES: To translate and validate French versions of two health-related quality of life questionnaires for patients with peripheral facial palsy: Facial Disability Index (FDI) and Facial Clinimetric Evaluation (FaCE) scale. DESIGN: Prospective cohort study. SETTING: University tertiary referral centre. PARTICIPANTS: A pilot test was performed on 10 subjects (5 patients with facial palsy of more than 1-month duration and 5 normal subjects), and then 67 adult patients with facial palsy were enrolled in the validation study. MAIN OUTCOME MEASURES: Translation of the original questionnaires has followed international guidelines using a forward-backward translation method. A pilot test and a validation study based on the translated questionnaires were performed. Internal consistency, test-retest reliability, validity and responsiveness were assessed. Validity was assessed by comparing to SF-36 and Sunnybrook/House-Brackmann grading systems. Subjects answered scales twice within a one-week interval. RESULTS: Sixty-seven patients were enrolled, among which 63 completed scales one week later (retest). For physical and social functions of FDI and FaCE scores, Cronbach's α representing internal consistency was 0.88, 0.70 and 0.89, and test-retest reliability by intra-class correlation coefficients was 0.81, 0.86 and 0.89, respectively. The correlation of facial movement score of FaCE scale was good with Sunnybrook/House-Brackmann grading systems (0.73 and -0.75, P < 0.01). The correlation of social function of FaCE scale was excellent with social function of SF-36 (0.8, P < 0.01). CONCLUSIONS: French versions of FDI and FaCE scale are psychometrically valid. Both questionnaires can be used for clinical studies to assess the quality of life of patients with peripheral facial palsy.

Tumor multifocality with vagus nerve involvement as a phenotypic marker of SDHD mutation in patients with head and neck paragangliomas: A 18 F-FDOPA PET/CT study.

BACKGROUND: 18 F-FDOPA PET/CT was proved to be a highly sensitive imaging method for detecting head and neck paraganglioma (HNPGL). The primary aim of the study was to evaluate the relationship between tumor characteristics and the SDHx-mutational status in a large series of patients with HNPGL evaluated by 18 F-FDOPA PET/CT. METHODS: A total of 104 patients with HNPGL (65 sporadic/39 SDHx-mutated) were included. RESULTS: In comparison to SDHB/SDC/SDHx-negative cases, patients with SDHD were younger at diagnosis and had a higher rate of multifocal, vagal, and carotid paraganglioma. In patients with SDHD, vagal paraganglia represented the primary site of tumor origin. Multicentric involvement of the vagus nerve alone or in association with other locations was found to be a typical feature of SDHD cases compared to other cases (odds ratio = 59.4). CONCLUSION: The present study shows that tumor multifocality within the vagus nerve is a phenotypic marker of SDHD mutation. This information is essential in the choice of the therapeutic strategy.

Adjunctive Gamma Knife Surgery or Wait and Scan Policy After Optimal Resection of Large Vestibular Schwannomas: Clinical and Radiologic Outcomes.

OBJECTIVES: Patients with large vestibular schwannomas (VSs) will require surgical treatment owing to the potential consequences of long tract and cranial nerve compression. We assessed the long-term clinical and radiologic outcomes of patients harboring large VSs treated with a facial nerve (FN)-sparing technique. METHODS: We performed a single-center retrospective cohort study of 169 consecutive large VSs treated surgically from January 2003 to May 2015. The postoperative volume of the tumor residue was assessed using thin-slice magnetic resonance imaging 6 months after surgery. Postoperatively, the patients were allocated to a wait and rescan (W&reS) or an upfront gamma knife surgery (GKS) policy. RESULTS: At the last follow-up examination, FN function was good (House-Brackmann grade I or II) in 84% of the patients. Of the 169 patients, 11% had undergone gross total resection, 59% near total, 21% subtotal, and 9% partial resection. In the 143 patients without gross total resection, the overall median tumor residue volume was 0.39 cm3. Of these 143 patients, 66 had been allocated to the W&reS policy and 77 to upfront GKS. Overall tumor control was achieved in 83% of cases, with a mean follow-up of 62 months. Of the 27 growing residues, 17 required salvage treatment (11% failure rate). The 1-, 5-, and 7-year progression-free survival rate was 95%, 82%, and 76% in the W&reS group and 99%, 81%, and 78% in the GKS group, respectively (P = 0.57). CONCLUSIONS: Functional nerve-sparing resection provides satisfactory FN preservation. The low probability of long-term regrowth of small remnants is an argument for a W&reS protocol. GKS is a legitimate option for salvage treatment.

Intracanalicular Vestibular Schwannomas: Initial Clinical Manifestation, Imaging Classification, and Risk Stratification for Management Proposal.

INTRODUCTION: There is no consensus about the use of observation as a therapeutic modality for intracanalicular vestibular schwannoma (ICVS). The objective of this study was to describe tumor evolution, its correlation with initial size, stage of vestibular schwannoma, clinical presentation and to propose a risk classification for tumor growth with a therapeutic decision algorithm. METHODS: Fifty-three patients with ICVS were followed prospectively from 2010 to 2015. The mean follow-up was 32 months. Patients underwent clinical examination, audiogram, magnetic resonance imaging at 6, 12, and then 12 months intervals within the first 5 years of initial diagnosis. We analyzed the patient's clinical course, audiologic changes, initial tumor location, and correlation of different parameters with ICVS growth. RESULTS: Fourteen patients (26%) deteriorated their hearing level and 17 patients (27%) showed tumor growth during the follow-up period. Growth was noted during the first year of observation in 13 patients (76.5%). Considering initial presentation: tumor size, intracanalicular staging, and hearing level, patients with larger vestibular schwannoma, extension to the fundus regardless of tumor size, higher initial pure-tone average, and speech recognition test showed a significantly higher rate of tumor growth. ICVS evolution was not correlated with hearing deterioration with time. DISCUSSION: We should consider observation a therapeutic modality. We valid the intrameatal staging as prognostic factor and propose a stratification of patients into low, moderate, or high risk for potential tumor growth to guide the initial management of ICVS.

Histological identification of nasopharyngeal mechanoreceptors.

The auditory tube plays a fundamental role in regulating middle ear pressure. A "system" sensitive to a pressure gradient between the middle ear and the ambient environment is necessary. The presence of mechanoreceptors in the middle ear and the tympanic membrane has been studied, but the presence of these receptors in the nasopharyngeal region remains unclear. The aim of this study is to confirm the presence of pressure sensitive corpuscles in the nasopharynx. An experimental study was conducted on five fresh and unembalded human cadavers. The pharyngeal ostium of the auditory tube and its periphery was removed in one piece by video-assisted endonasal endoscopy. Samples were fixed in formaldehyde solution, embedded in paraffin, and cut. Slides were analyzed by HES (Hematoxyline Eosine Safran) coloration, by S100 protein and neurofilament protein immunostaining. Encapsulated nerve endings were researched and identified by slides analysis. Eight samples were included in our study. On seven samples, Ruffini corpuscles were identified in the mucosa of the posterior area of the pharyngeal ostium, with a higher concentration in the pharyngeal recess and in the posterior nasopharyngeal wall. Our study identified nasopharyngeal mechanoreceptors that could detect the nasopharyngeal pressure and, by extension, the atmospheric pressure. These findings support the theory of the neuronal reflex arc of isobaric system of the middle ear, based on the existence of a "system" sensitive to a pressure gradient between the middle ear and the ambient environment. Understanding of this system has been helpful in the diagnosis and management of middle ear diseases.

Prospective comparison of (68)Ga-DOTATATE and (18)F-FDOPA PET/CT in patients with various pheochromocytomas and paragangliomas with emphasis on sporadic cases.

PURPOSE: Pheochromocytomas/paragangliomas (PHEOs/PGLs) overexpress somatostatin receptors and recent studies have already shown excellent results in the localization of these tumors using (68)Ga-labeled somatostatin analogs ((68)Ga-DOTA-SSA), especially in patients with germline succinate dehydrogenase subunit B gene (SDHB) mutations and head and neck PGLs (HNPGLs). The value of (68)Ga-DOTA-SSA has to be established in sporadic cases, including PHEOs. Thus, the aim of this study was to compare (68)Ga-DOTATATE PET/CT, (18)F-FDOPA PET/CT, and conventional imaging in patients with various PHEOs/PGLs with a special emphasis on sporadic cases, including those located in the adrenal gland. DESIGN: (68)Ga-DOTATATE, (18)F-FDOPA PET/CT, and conventional imaging (contrast-enhanced CT and MRI with MR angiography sequences) were prospectively performed in 30 patients (8 with SDHD mutations, 1 with a MAX mutation and 21 sporadic cases) with PHEO/PGL at initial diagnosis or relapse. RESULTS: The patient-based sensitivities were 93 % (28/30), 97 % (29/30), and 93 % (28/30) for (68)Ga-DOTATATE PET/CT, (18)F-FDOPA PET/CT, and conventional imaging, respectively. The lesion-based sensitivities were 93 % (43/46), 89 % (41/46), and 76 % (35/46) for (68)Ga-DOTATATE PET/CT, (18)F-FDOPA PET/CT, and conventional imaging respectively (p = 0.042). (68)Ga-DOTATATE PET/CT detected a higher number of HNPGLs (30/30) than (18)F-FDOPA PET/CT (26/30; p = 0.112) and conventional imaging (24/30; p = 0.024). (68)Ga-DOTATATE PET/CT missed two PHEOs of a few millimeters in size and a large recurrent PHEO. One lesion was considered false-positive on (68)Ga-DOTATATE PET/CT and corresponded to a typical focal lesion of fibrous dysplasia on MRI. Among the 11 lesions missed by conventional imaging, 7 were detected by conventional imaging with knowledge of the PET results (4 HNPGLs, 2 LNs, and 1 recurrent PHEO). CONCLUSION: (68)Ga-DOTATATE PET/CT is the most sensitive tool in the detection of HNPGLs, especially SDHD-related tumors, which may be very small and fail to concentrate sufficient (18)F-FDOPA. The present study further expands the use of (68)Ga-DOTATATE for all patients with HNPGLs, regardless of their genotype. (68)Ga-DOTATATE PET/CT may be inferior to (18)F-FDOPA PET/CT in the detection PHEOs.

Magnetic resonance spectroscopy of paragangliomas: new insights into in vivo metabolomics.

Paragangliomas (PGLs) can be associated with mutations in genes of the tricarboxylic acid (TCA) cycle. Succinate dehydrogenase (SDHx) mutations are the prime examples of genetically determined TCA cycle defects with accumulation of succinate. Succinate, which acts as an oncometabolite, can be detected by ex vivo metabolomics approaches. The aim of this study was to evaluate the potential role of proton magnetic resonance (MR) spectroscopy ((1)H-MRS) for identifying SDHx-related PGLs in vivo and noninvasively. Eight patients were prospectively evaluated with single voxel (1)H-MRS. MR spectra from eight tumors (four SDHx-related PGLs, two sporadic PGLs, one cervical schwannoma, and one cervical neurofibroma) were acquired and interpreted qualitatively. Compared to other tumors, a succinate resonance peak was detected only in SDHx-related tumor patients. Spectra quality was considered good in three cases, medium in two cases, poor in two cases, and uninterpretable in the latter case. Smaller lesions had lower spectra quality compared to larger lesions. Jugular PGLs also exhibited a poorer spectra quality compared to other locations. (1)H-MRS has always been challenging in terms of its technical requisites. This is even more true for the evaluation of head and neck tumors. However, (1)H-MRS might be added to the classical MR sequences for metabolomic characterization of PGLs. In vivo detection of succinate might guide genetic testing, characterize SDHx variants of unknown significance (in the absence of available tumor sample), and even optimize a selection of appropriate therapies.

Vitamin D3 potentiates myelination and recovery after facial nerve injury.

Roles of vitamin D on the immune and nervous systems are increasingly recognized. Two previous studies demonstrated that ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) induced functional recovery and increased myelination in a rat model of peroneal nerve transection. The current report assessed whether cholecalciferol was efficient in repairing transected rabbit facial nerves. Animals were randomized into two groups of rabbits with an unilateral facial nerve surgery: the vitamin D group included animals receiving a weekly oral bolus of vitamin D3 (200 IU/kg/day), from day 1 post-surgery; the control group included animals receiving a weekly oral bolus of vehicle (triglycerides). Contralateral unsectioned facial nerves from all experimental animals were used as controls for the histological study. The facial functional index was measured every week while the inner diameter of myelin sheath and the G ratio were quantified at the end of the 3 month experiment. The current report indicates that cholecalciferol significantly increases functional recovery and myelination, after 12 weeks of treatment. To the best of our knowledge, this is the first study investigating the therapeutic benefit of vitamin D supplementation in an animal model of facial paralysis. It paves further the way for clinical trials based on the administration of this steroid in individuals with injured facial nerves.