Publications by authors named "Jean Paul Marie"

63 Publications

Comparison of the effects of two therapeutic strategies based on olfactory ensheathing cell transplantation and repetitive magnetic stimulation after spinal cord injury in female mice.

J Neurosci Res 2021 May 7. Epub 2021 May 7.

Normandie Univ, UNIROUEN, EA3830-GRHV, Rouen, France.

Spinal cord injury (SCI) is a debilitating condition, which leads to a permanent loss of functions below the injury site. The events which take place after SCI are characterized by cellular death, release of inhibitory factors, and inflammation. Many therapies have been studied to cure SCI, among them magnetic stimulation aims to reduce the secondary damages in particular by decreasing apoptosis, while, cellular transplantation promotes neuroregeneration by enhancing axonal regrowth. In the present study, we compared individually primary olfactory ensheathing cell (OEC) transplantation and repetitive trans-spinal magnetic stimulation (rTSMS) and then, we combined these two therapeutic approaches on tissue repair and functional recovery after SCI. To do so, SCIs were performed at Th10 level on female C57BL/6 mice, which were randomized into four groups: SCI, SCI + primary bOECs, SCI + STM, SCI + primary bulbar olfactory ensheathing cells (bOECs) + stimulation (STM). On these animals bioluminescence, immunohistological, and behavioral experiments were performed after SCI. Our results show that rTSMS has beneficial effect on the modulation of spinal scar by reducing fibrosis, demyelination, and microglial cell activation and by increasing the astroglial component of the scar, while, primary bOEC transplantation decreases microglial reactivity. At the opposite, locotronic experiments show that both treatments induce functional recovery. We did not observed any additional effect by combining the two therapeutic approaches. Taken together, the present study indicates that primary bOEC transplantation and rTSMS treatment act through different mechanisms after SCI to induce functional recovery. In our experimental paradigm, the combination of the two therapies does not induce any additional benefit.
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http://dx.doi.org/10.1002/jnr.24836DOI Listing
May 2021

Anesthetic Management for Awake Tubeless Suspension Microlaryngoscopy.

Laryngoscope 2021 Apr 21. Epub 2021 Apr 21.

Department of Otorhinolaryngology-Head and Neck Surgery, Rouen University Hospital, Rouen, France.

Objectives/hypothesis: Patients' eligibility for bilateral selective laryngeal reinnervation surgery is evaluated by suspension microlaryngoscopy (SML) examination with laryngeal electromyography (LEMG). Maintaining spontaneous ventilation, with remifentanil sedation/analgesia without endotracheal tube, to allow the patient to phonate with the surgeon during awake, LEMG is a major challenge for the anesthesiologist and the otorhinololaryngologist. The objective of this study was to evaluate the safety and efficacy of a novel anesthesia protocol to manage airway access during awake tubeless SML.

Study Design: Retrospective study.

Methods: Anesthesia records of patients undergoing awake SML with LEMG were retrospectively analyzed. Procedures were performed with remifentanil sedation/analgesia with targeted controlled infusion (TCI) in combination with local anesthesia. The main outcome was the failure rate of the anesthesia protocol during the procedure. Secondary outcomes were as follows: rate of apnea requiring ventilation, airway bleeding, regurgitation, hemodynamic data as well as vasopressor use, complications, and surgeon satisfaction with the procedure.

Results: Data were obtained for 39 patients between November 2017 and September 2019, the mean age was 52 years and 29 (74%) were female. All procedures were completed without complications (0% [0-9]). Three patients (8% [1.6-20.8]) had an intraoperative episode of hypoxemia requiring mask reventilation. There was no airway bleeding, no regurgitation, and no hypotensive episode. Three patients (8% [1.6-20.8]) had noninvasive ventilation for respiratory distress after the end of the procedure.

Conclusions: Our results show that awake tubeless SML allowing phonation during LEMG can be realized under sedation and local anesthesia. However, further data are needed concerning the intraoperative and postoperative safety of the procedure.

Level Of Evidence: 4. Laryngoscope, 2021.
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http://dx.doi.org/10.1002/lary.29565DOI Listing
April 2021

European white paper: oropharyngeal dysphagia in head and neck cancer.

Eur Arch Otorhinolaryngol 2021 Feb 19;278(2):577-616. Epub 2020 Dec 19.

Head and Neck Oncology Service, Candiolo Cancer Institute, FPO - IRCCS, Candiolo, TO, Italy.

Purpose: To develop a European White Paper document on oropharyngeal dysphagia (OD) in head and neck cancer (HNC). There are wide variations in the management of OD associated with HNC across Europe.

Methods: Experts in the management of specific aspects of OD in HNC across Europe were delegated by their professional medical and multidisciplinary societies to contribute to this document. Evidence is based on systematic reviews, consensus-based position statements, and expert opinion.

Results: Twenty-four sections on HNC-specific OD topics.

Conclusion: This European White Paper summarizes current best practice on management of OD in HNC, providing recommendations to support patients and health professionals. The body of literature and its level of evidence on diagnostics and treatment for OD in HNC remain poor. This is in the context of an expected increase in the prevalence of OD due to HNC in the near future. Contributing factors to increased prevalence include aging of our European population (including HNC patients) and an increase in human papillomavirus (HPV) related cancer, despite the introduction of HPV vaccination in various countries. We recommend timely implementation of OD screening in HNC patients while emphasizing the need for robust scientific research on the treatment of OD in HNC. Meanwhile, its management remains a challenge for European professional associations and policymakers.
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http://dx.doi.org/10.1007/s00405-020-06507-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826315PMC
February 2021

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

Plast Reconstr Surg 2020 12;146(6):1295-1305

From the Institute for Research and Innovation in Biomedicine and the Department of Immunology and Biotherapy, Normandie University; the Department of Otorhinolaryngology and Head Neck Surgery, Rouen University Hospital; the Department Otorhinolaryngology and Head Neck Surgery, Conception University Hospital; Aix Marseille University, INP, CNRS UMR 7051; and APHM, Culture and Cell Therapy Laboratory.

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.
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http://dx.doi.org/10.1097/PRS.0000000000007367DOI Listing
December 2020

Immediate Intraoperative Repair of the Recurrent Laryngeal Nerve in Thyroid Surgery.

Laryngoscope 2021 06 29;131(6):1429-1435. Epub 2020 Oct 29.

Department of Otorhinolaryngology Head and Neck Surgery, University of Udine School of Medicine, Udine, Italy.

Objectives: Recurrent laryngeal nerve (RLN) injury is a recognized risk during thyroid and parathyroid surgery and can result in significant morbidity. The aim of this review paper is to consider the optimal approach to the immediate intraoperative repair of the RLN during thyroid surgery.

Methods: A PubMed literature search was performed from inception to June 2020 using the following search strategy: immediate repair or repair recurrent laryngeal nerve, repair or reinnervation recurrent laryngeal nerve and immediate neurorraphy or neurorraphy recurrent laryngeal nerve.

Results: Methods of immediate intraoperative repair of the RLN include direct end-to-end anastomosis, free nerve graft anastomosis, ansa cervicalis to RLN anastomosis, vagus to RLN anastomosis, and primary interposition graft. Techniques of nerve repair include micro-suturing, use of fibrin glue, and nerve grafting. Direct micro-suture is preferable when the defect can be repaired without tension. Fibrin glue has also been proposed for nerve repair but has been criticized for its toxicity, excessive slow reabsorption, and the risk of inflammatory reaction in the peripheral tissues. When the proximal stump of the RLN cannot be used, grafting could be done using transverse cervical nerve, supraclavicular nerve, vagus nerve, or ansa cervicalis.

Conclusions: Current evidence is low-level; however, it suggests that when the RLN has been severed, avulsed, or sacrificed during thyroid surgery it should be repaired intraoperatively. The immediate repair has on balance more advantages than disadvantages and should be considered whenever possible. This should enable the maintenance of vocal cord tone, better and prompter voice recovery and avoidance of aspiration. Laryngoscope, 131:1429-1435, 2021.
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http://dx.doi.org/10.1002/lary.29204DOI Listing
June 2021

Early Management of Acute Unilateral Vocal Fold Paralysis: Update of the Literature.

J Voice 2020 Apr 3. Epub 2020 Apr 3.

Unit of Otorhinolaryngology-Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal; Research Group on Ventilatory Handicap (EA 3830 GRHV), University of Rouen, Normandy, France; University Hospital Federation SURFACE, Regenerative surgery in Head and Neck, Amiens, France.

Background: Unilateral vocal fold paralysis (UVFP) often leads to significant morbidity that may include dysphonia, swallowing problems and aspiration. The best timing for medialization procedures is still controversial. Published data suggest that early intracordal injection positively affects long-term outcomes.

Objectives: To critically review current literature in order to determine if early treatment of acute UVFP influences clinical outcomes of the patients.

Type Of Review: Nonsystematic literature review.

Methods: A literature review was performed, using the Pubmed database. All relevant articles published in English addressing the effect of early treatment in acute unilateral focal fold paralysis were analyzed. Twenty-six articles were included due to their scientific interest.

Results: Published literature suggests that early intracordal injection in patients with UVFP reduces pulmonary infections, hospital length of stay and improves voice parameters. Also, patients who receive early intracordal injection seem to be less likely to undergo subsequent medialization thyroplasty.

Conclusions: Early intracordal injection should be offered to patients with newly diagnosed UVFP since it promotes a satisfactory position of the vocal fold and seems to improve clinical outcomes. More investigation, with long-term follow up data and treatment randomization, is necessary to develop clinical consensus for these patients.
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http://dx.doi.org/10.1016/j.jvoice.2020.02.021DOI Listing
April 2020

Bilateral Selective Laryngeal Reinnervation for Bilateral Vocal Fold Paralysis in Children.

JAMA Otolaryngol Head Neck Surg 2020 05;146(5):401-407

Research Group on Ventilatory Handicap (EA 3830 GRHV), The Rouen Institute for Research and Innovation in Biomedicine, Rouen, Normandy, France.

Importance: Bilateral vocal fold paralysis (BVFP) in pediatric patients is a challenging entity with multiple causes. Traditional approaches to managing BVFP include tracheostomy, arytenoidectomy, suture lateralization, cordotomy, and posterior cricoid enlargement. These interventions are used to create a stable airway but risk compromising voice quality.

Objectives: To assess the use of bilateral selective laryngeal reinnervation (SLR) surgery to manage BVFP and restore dynamic function to the larynx in pediatric patients.

Design, Setting, And Participants: In this case series performed at 2 tertiary care academic institutions, 8 pediatric patients underwent bilateral SLR to treat BVFP (5 patients with iatrogenic BVFP and 3 with congenital BVFP) from November 2004 to August 2018 with follow-up for at least 1.5 years.

Interventions: Bilateral selective laryngeal reinnervation surgery.

Main Outcomes And Measures: Flexible laryngoscopy findings, subjective and objective measures of voice quality, subjective swallowing function, and decannulation in patients who were previously dependent on a tracheostomy tube.

Results: Participants included 6 boys and 2 girls with a median age of 9.3 (range, 2.2 to 18.0) years at the time of surgery. All 8 patients were decannulated; 6 patients had preoperative tracheostomies and 2 had perioperative tracheostomies. Voice quality, as measured using the GRBAS (grade, roughness, breathiness, asthenia, strain) scale, improved in 6 of 8 patients after reinnervation, and swallowing was not impaired in any patients. In 2 patients, GRBAS scale scores remained the same before and after surgery. Inspiratory vocal fold abduction was observed on both sides in 5 patients and on 1 side in 2 patients, with no active abduction observed in 1 patient. The follow-up period was more than 5 years in 7 of 8 patients and at least 1.5 years in all patients.

Conclusions And Relevance: Bilateral SLR appears to be a promising treatment option for children with BVFP; it is currently the only option, to our knowledge, with the potential to restore abductor and adductor vocal fold movement. In patients with complete paralysis, this procedure may provide a strategy for airway management and restoration of the dynamic function of the larynx. It could be considered as a first-line technique before endolaryngeal or airway framework procedures, which carry a risk of compromising voice quality.
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http://dx.doi.org/10.1001/jamaoto.2019.4863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243085PMC
May 2020

A prospective multicentre REFCOR study of 470 cases of head and neck Adenoid cystic carcinoma: epidemiology and prognostic factors.

Eur J Cancer 2020 05 11;130:241-249. Epub 2020 Mar 11.

Sorbonne University, APHP, Department of ENT-Head and Neck Surgery, Tenon Hospital, 4 Rue de La Chine, 75020, Paris, France. Electronic address:

Background: Adenoid cystic carcinoma (ACC) accounts for 1% of malignant head and neck tumours [1] and 10% of salivary glands malignant tumours. The main objective of our study is to investigate the prognostic factors influencing the event-free survival (EFS) of patients with ACC.

Patients And Methods: A multicentre prospective study was conducted from 2009 to 2018. All 470 patients with ACC whose survival data appear in the REFCOR database were included in the study. The main judgement criterion was EFS. Both a bivariate survival analysis using log-rank test and a multivariate using Cox model were performed using the R software.

Results: Average age was 55 years. Females accounted for 59.4% of the cohort. The body mass index (BMI) was normal in 86% of cases. Tumours were located in minor salivary glands in 60% of cases. T3/T4 stages represented 58%; 89% of patients were cN0. histological grade III was observed on 21% of patients. The EFS and overall 5-year survival rates were 50% and 85%, respectively. After adjustment, the most significant pejorative prognostic factors were age ≥65 years (hazard ratio [HR] = 1.67), BMI<16.5 (HR = 2.62), and lymph node invasion cN (HR = 2.08).

Conclusion: Age, BMI and N stage are the three main clinical prognostic factors determining EFS identified in this prospective series of patients with ACC. Such findings open new research perspectives on the influence of these components on initial patient care.
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http://dx.doi.org/10.1016/j.ejca.2020.01.023DOI Listing
May 2020

Assessment of bilateral vocal fold immobility prior to selective bilateral laryngeal reinnervation.

Clin Otolaryngol 2020 05 7;45(3):432-435. Epub 2020 Mar 7.

Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital of Rouen, Rouen, France.

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http://dx.doi.org/10.1111/coa.13516DOI Listing
May 2020

Olfactory Ecto-Mesenchymal Stem Cells in Laryngeal Nerve Regeneration in Rats.

J Voice 2021 May 22;35(3):349-359. Epub 2019 Nov 22.

Department of Otorhinolaryngology-Head and Neck Surgery, University Hospital of Rouen, Rouen, France.

Selective intralaryngeal reinnervation has been shown to be effective in experimental models. This consists of independently reinnerving the adductor and abductor of laryngeal muscles of the larynx, in order to prevent any misalignment of the axonal regrowth, improve the functional recovery and tend toward reduction of synkinesis. The surgical technique remains complex. Current research focuses on simplifying and improving this technique. Olfactory ectomesenchymal stem cells (OEMSC) represent an interesting candidate for cell therapy and could be obtained from olfactory mucosa. Recent reports suggest a neuroregenerative potential in various animal models of central and peripheral nervous systems injuries. The aim of this study was dual: to develop a simple surgical model of selective reinnervation applicable in humans and to evaluate the relevance of OEMSC-based cell therapy for improving axonal guidance. Eight Fisher syngeneic rats were used to carry out the OEMSCs culture. Thirty-four Fisher syngeneic rats were operated on, divided into three groups depending on the transplanting. For all the rats, we have performed a side to end anastomosis of the vagal nerve with the inferior laryngeal nerve by interposition of a nerve graft from the left femoral nerve. Then, the first group didn't have any injection, the second group has an injection of thrombin and the third group has an injection of one million EOMSCs. Three months after surgery, laryngeal muscle activity was evaluated by videolaryngoscopy and electromyography recordings. In order to illustrate the quality of axonal regrowth, a fluorescent tracer was injected into the right posterior crico-arytenoid muscle (PCA) to reveal the cellular bodies of the motoneurons responsible for reinnervation of the PCA in the central nervous system. In our study, no improvement was found during the videolaryngological functional evaluation or with regard to the electrical activity of the PCA muscle. The cells colabelled in retrograde tracing were numerous in all groups, reflecting abnormal axonal regeneration. The interposition of a nerve graft, as side to end anastomosis between the vagus nerve and the inferior laryngeal nerve, filled with OEMSCs, does not provide better reinnervation of a hemilarynx.
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http://dx.doi.org/10.1016/j.jvoice.2019.10.012DOI Listing
May 2021

Nonselective Reinnervation as a Primary or Salvage Treatment of Unilateral Vocal Fold Palsy.

Laryngoscope 2020 07 21;130(7):1756-1763. Epub 2019 Oct 21.

Department of Otorhinolaryngology-Head and Neck Surgery, University Hospital of Rouen, Rouen, France.

Objectives/hypothesis: Demonstration of voice improvement and long-term stability following nonselective unilateral laryngeal reinnervation (ULR) in patients with unilateral vocal fold paralysis (UVFP) and severe denervation. A subgroup of patients on whom ULR was performed as a salvage technique following unsuccessful medialization was analyzed separately.

Study Design: Prospective cohort study.

Methods: The ansa cervicalis-recurrent laryngeal nerve anastomosis technique was performed in all patients. Pre- and postoperative voice analysis included voice questionnaires, voice assessment by senior laryngologists using the Hirano Voice Scale, and computer-assisted voice analysis at defined time points over the course of 36 months. Laryngeal electromyography (LEMG) and spirometry were performed before and 1 year after ULR.

Results: Significant linear improvement of mean voice quality over time was observed in the majority of parameters measured in 48 ULR patients and in eight ULR salvage patients. LEMG 1 year after ULR showed new recruitment. Mean voice quality remained stable during follow-up in all ULR patients and in the ULR salvage group.

Conclusions: Nonselective ULR in UVFP is a reliable and stable therapeutic option for patients with high expectations concerning voice quality. The effect is stable in long-term results. It is also a viable option for patients in whom conventional voice surgery failed to improve voice quality. We therefore propose ULR as salvage option in UVFP.

Level Of Evidence: 2b Laryngoscope, 130:1756-1763, 2020.
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http://dx.doi.org/10.1002/lary.28324DOI Listing
July 2020

Clinical and Radiological Characteristics of Malignant Tumors Located to the Cerebellopontine Angle and/or Internal Acoustic Meatus.

Otol Neurotol 2019 10;40(9):1237-1245

Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Center of Neurosensorial-Head and Neck Diseases, Lariboisière Hospital, University Paris 7 Paris Diderot, Assistance Publique des Hôpitaux de Paris & EA7334 Patient-Reported Outcomes, University Paris 7 Diderot University, Sorbonne Paris Cité, Paris.

Objective: Metastatic lesions to the internal auditory meatus (IAM) and/or the cerebellopontine angle (CPA) are rare and may appear like a vestibular schwannoma (VS). We herein raise the issue of the diagnosis and treatment of nine malignant cases of the CPA and IAM among three referral centers in France and Japan. The aim of this study was 1) to report malignant lesions of the CPA, their diagnosis and treatment, 2) to review the literature, 3) to propose criteria of suspicion for malignant tumors of the CPA.

Methods: Nine patients who had malignant lesions of the CPA and/or IAM for whom the final diagnosis was made by surgery, lumbar puncture, or PET scan were included. The main outcomes measured were: rapid onset of symptoms, association of cochlea-vestibular symptoms with facial palsy, and MRI analysis.

Results: Among the nine patients with malignant tumor of the CPA, 8 of them (89%) had a facial palsy associated with cochlea-vestibular symptoms. Rapid growth of the tumor was observed in 77% (7/9) of the cases in a mean time interval of 4.6 months. The initial diagnosis evoked was VS in 44% of the cases (4/9). Atypical MRI aspect was seen in 67% of the cases (6/9) with bilateral tumors in 55% of cases (5/9).

Conclusion: Although rare, malignant tumors of the CPA and/or IAM should be evoked in case of association of cochleovestibular symptoms and facial palsy, rapid onset and atypical MRI aspect.
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http://dx.doi.org/10.1097/MAO.0000000000002360DOI Listing
October 2019

Inhibition of ADAMTS-4 Expression in Olfactory Ensheathing Cells Enhances Recovery after Transplantation within Spinal Cord Injury.

J Neurotrauma 2020 02 27;37(3):507-516. Epub 2019 Aug 27.

Normandie Univ, UNIROUEN, GRHV EA3830; Institute for Research and Innovation in Biomedicine (IRIB), Rouen, France.

Spinal cord injury (SCI) induces permanent loss of sensitive and motor functions below the injury level. To date, a wide variety of cells has been used as biotherapies to cure SCI in different animal paradigms. Specifically, olfactory ensheathing cells (OECs) is one of the most promising. Indeed, OECs have been shown to enhance recovery in many animal studies. Moreover, OECs transplantation has been applied to a paraplegic patient and have shown beneficial effects. However, it has been reported that the significant level of recovery varies among different patients. Therefore, it is of primary importance to enhance the regenerative efficiency of OECs for better translations. Recently, it has been shown that inhibiting ADAMTS4 expression in glial cells increases their synthesis of neurotrophic factors. We hypothesized that the expression of neurotrophic factors secreted by OECs can be increased by the deletion of ADAMTS4. Taking advantage of ADAMTS4 mouse line, we produce ADAMTS4 deficient primary OEC cultures and then we investigated their regenerative potential after SCI. By using quantitative polymerase chain reaction, bioluminescence imaging, measurement of locomotor activity, electrophysiological studies, and immunohistochemistry, our results show that ADAMTS4 olfactory bulb OEC (bOECs) primary cultures upregulate their trophic factor expression , and that the transplantation of ADAMTS4 bOECs in a severe SCI model increases functional recovery and tissue repair . Altogether, our study reveals, for the first time, that primary bOEC cultures transplantation can be potentialized by inhibition of the expression of ADAMTS4.
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http://dx.doi.org/10.1089/neu.2019.6481DOI Listing
February 2020

Benefit of cetuximab addition to a platinum-fluorouracil-based chemotherapy according to KRAS-LCS6 variant in an unselected population of recurrent and/or metastatic head and neck cancers.

Eur Arch Otorhinolaryngol 2019 Feb 6;276(2):541-550. Epub 2018 Dec 6.

IRON Group, Normandy Centre for Genomic and Personalized Medicine, Rouen University Hospital, UNIROUEN, Inserm U1245, rue de Germont, Normandie Université, 76000, Rouen, France.

Objectives: To evaluate the benefit of cetuximab (Cx) addition to platinum-based and 5-fluorouracil chemotherapy (PFU) in unselected recurrent and/or metastatic head and neck cancer patients (R/MHNC) according to KRAS-LCS6 variant status.

Methods: All patients who received at least two PFU ± Cx cycles from 2004 to 2014 were retrospectively included into to two distinct study periods according to Cx implementation: patients treated by PFU alone before 2009 and those treated by PFU + Cx from 2009. Primary objective was to evaluate the progression-free survival (PFS) between the two groups. Secondary objectives were to analyze the overall survival (OS) between the two groups and the prognostic impact of KRAS-LCS6 variant. Factors associated with survival were determined by a Cox multivariate analysis including age, WHO performance status (PS), type of treatment, KRAS-LCS6 variant, Charlson's score and p16 status.

Results: Overall, 134 patients were included: 59 (44%) in PFU group and 75 (56%) in PFU + Cx group. Baseline characteristics were well balanced including 30% of patients with 2-3 PS. Median PFS was significantly improved in PFU + Cx group compared to PFU group (6.1 vs 4.4 months, respectively, HR 0.68, p = 0.02) and with a trend for better OS. A KRAS-LCS6 variant was found in 27 (25%) of samples without prognostic impact neither in whole population nor according to treatment. In multivariate analysis, addition of Cx to PFU was the only factor significantly associated with a better PFS (p = 0.01, HR 0.6).

Conclusion: Our results suggest that PFU + Cx combination may be effective in unselected population of R/MHNC regardless the KRAS-LCS6 variant status.
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http://dx.doi.org/10.1007/s00405-018-5235-6DOI Listing
February 2019

Selective laryngeal reinnervation: can rerouting of the thyrohyoid nerve simplify the procedure by avoiding the use of a nerve graft?

Surg Radiol Anat 2019 Feb 29;41(2):145-150. Epub 2018 Oct 29.

Department of Otorhinolaryngology, Rouen University Hospital, 1 rue de Germont, 76031, Rouen, France.

Purpose: The objective of this study was to record the descriptive and metric anatomical characteristics of the thyrohyoid nerve with the aim of rerouting it in a selective laryngeal reinnervation procedure.

Methods: An anatomical study was performed on ten formalin-embalmed cadavers. The origin of the thyrohyoid nerve and the superior root of the ansa cervicalis, the location of the thyrohyoid nerve ending in the thyrohyoid muscle, and the recurrent laryngeal nerve were established. Then, a rerouting of the thyrohyoid nerve was performed. We measured the length of thyrohyoid nerve, the distance between the thyrohyoid nerve ending and the recurrent laryngeal nerve at the horizontal level of the cricothyroid joint before and after the rerouting, and the distance between the origin of the thyrohyoid nerve and the superior root of the ansa cervicalis.

Results: The thyrohyoid nerve was identified on both sides in all the cases. The average length of the thyrohyoid nerve was 27 mm. The end of the thyrohyoid nerve was found in 100% of the cases at the upper outer quarter of the thyrohyoid muscle. After the rerouting, an average reduction of 30% of the distance between the end of the thyroid nerve and the recurrent laryngeal nerve at the horizontal level of the cricothyroid joint was measured.

Conclusion: The rerouting of the thyrohyoid nerve provided a reduction in the length of the nerve graft in laryngeal reinnervation. Moreover, the constancy of the thyrohyoid nerve and its characteristics make it a valuable anatomical base for laryngeal reinnervation and laryngeal innervated allotransplantation.
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http://dx.doi.org/10.1007/s00276-018-2117-yDOI Listing
February 2019

Dual innervation may occur in a partially denervated muscle.

Muscle Nerve 2019 01 28;59(1):108-115. Epub 2018 Nov 28.

Normandie University, UNIROUEN, Institute for Research and Innovation in Biomedicine (IRIB), EA3830-GRHV, 76000 Rouen, France.

Introduction: With a view to simplifying surgical techniques for selective laryngeal reinnervation, we addressed the question of whether it is feasible to receive additional innervation by a partially denervated muscle using an infrahyoid muscle model.

Methods: In 90 rats (6 groups of 15), phrenic nerve transfer was used to reinnervate the sternothyroid muscle. In some cases, residual innervation by the original nerve was present. Three months later we performed electromyographic studies, contraction strength measurements, histologic assessment, and retrograde labeling.

Results: Muscles reinnervated by the phrenic nerve had a greater "dual-response" rate (in terms of nerve latency, contraction strength, and retrograde labeling) than muscles in the control groups.

Discussion: The phrenic nerve can impart its inspiratory properties to an initially denervated strap muscle-even when residual innervation is present. The preservation of contractile potential confirmed the feasibility of dual innervation in a previously injured muscle. Muscle Nerve 59:108-115, 2019.
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http://dx.doi.org/10.1002/mus.26323DOI Listing
January 2019

Reinnervation of the diaphragm by the inferior laryngeal nerve to the phrenic nerve in ventilator-dependent tetraplegic patients with C3-5 damage.

ERJ Open Res 2017 Oct 20;3(4). Epub 2017 Nov 20.

AP-HP, Groupe Hospitalier Pitié-Salpêtrière Charles Foix, Service de Pneumologie et Réanimation Médicale (Département "R3S"), Paris, France.

The aim of this study was to evaluate the feasibility of unilateral diaphragmatic reinnervation in humans by the inferior laryngeal nerve. This pilot study included chronically ventilated tetraplegic patients with destruction of phrenic nerve motoneurons. Five patients were included. They all had a high level of tetraplegia, with phrenic nerve motor neuron destruction. They were highly dependent on ventilation, without any possibility of weaning. They did not have other chronic pathologies, especially laryngeal disease. They all had diaphragmatic explorations to diagnose the destruction of the motoneurons of the phrenic nerves and nasoendoscopy to be sure that they did not have laryngeal or pharyngeal disease. Then, surgical anastomosis of the right phrenic nerve was performed with the inferior laryngeal nerve, by a cervical approach. A laryngeal reinnervation was performed at the same time, using the ansa hypoglossi. One patient was excluded because of a functional phrenic nerve and one patient died 6 months after the surgery of a cardiac arrest. The remaining three patients were evaluated after the anastomosis every 6 months. They did not present any swallowing or vocal alterations. In these three patients, the diaphragmatic explorations showed that there was a recovery of the diaphragmatic electromyogram of the right and left hemidiaphragms after 1 year. Two patients had surgical diaphragmatic explorations for diaphragmatic pacing 18-24 months after the reinnervation with excellent results. At 36 months, none of the patients could restore their automatic ventilation. In conclusion, this study demonstrated that diaphragmatic reinnervation by the inferior laryngeal nerve is effective, without any vocal or swallowing complications.
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http://dx.doi.org/10.1183/23120541.00052-2017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5699880PMC
October 2017

Implication of the vagus nerve in breathing pattern during sequential swallowing in rats.

Physiol Behav 2017 Oct 8;179:434-441. Epub 2017 Jul 8.

EA 3830, Research Group on Ventilatory Handicap (GRHV), Rouen University, Rouen, France; CRMPR les Herbiers, Ugecam group, Bois-Guillaume, France; Pôle 3R, Rouen University Hospital, Rouen, France.

The ventilatory pattern during sequential swallowing is influenced by the vagal activity. As the vagus nerve is paired and mixed, we aimed (1) to determine if vagal implication in swallowing and breathing coordination is symmetric. (2) to study the importance of vagal afferences in swallowing and breathing coordination. Sixty two Wistar rats (7-11weeks, 260-400g) were studied by barometric plethysmography. In the first part of the study, we determined the effects of a right cervical vagotomy and the effects of a left cervical vagotomy on ventilatory pattern at rest and during sequential swallowing (14 rats with right vagotomy, 14 rats with left vagotomy and 14 rats with sham surgery). Comparisons of ventilatory variables were made between right and left vagotomized animals. Thereafter, we determined the effects of electrical vagus nerve stimulation (VNS) on ventilatory pattern at rest and during sequential swallowing (10 rats with electrical VNS and 10 rats with sham VNS). We showed that a right or a left cervical vagotomy does not alter ventilation at rest, but induces during sequential swallowing a decrease in respiratory rate (RR) (p<0.001) and mean inspiratory flow (VT/TI) (p<0.01) compared to baseline. These modifications were not observed following sham surgery and there were no differences in ventilatory variables at rest and during sequential swallowing between right vagotomized rats and left vagotomized rats (p>0.05). Electrical VNS had no effect on ventilation at rest, but it minimized during sequential swallowing a decrease in RR related to a local alteration of the vagus nerve after placement of the electrodes as shown following sham VNS. In conclusion, the implication of vagus nerve in breathing pattern during sequential swallowing seems symmetric and influenced by activation of the vagal afferent pathway. These data can be useful when testing electrical VNS in swallowing disorders.
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http://dx.doi.org/10.1016/j.physbeh.2017.07.014DOI Listing
October 2017

Oropharyngeal dysphagia: when swallowing disorders meet respiratory diseases.

Eur Respir J 2017 04 12;49(4). Epub 2017 Apr 12.

Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Hospitalier Pitié-Salpêtrière Charles Foix, Service de Chirurgie Maxilo faciale (Département "R3S"), Paris, France.

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http://dx.doi.org/10.1183/13993003.02530-2016DOI Listing
April 2017

Feasibility, repeatability, and safety of ultrasound-guided stimulation of the first cervical nerve at the alar foramen in horses.

Am J Vet Res 2016 Nov;77(11):1245-1251

OBJECTIVE To develop and assess the feasibility, repeatability, and safety of an ultrasound-guided technique to stimulate the first cervical nerve (FCN) at the level of the alar foramen of the atlas of horses. ANIMALS 4 equine cadavers and 6 clinically normal Standardbreds. PROCEDURES In each cadaver, the FCN pathway was determined by dissection, and any anastomosis between the first and second cervical nerves was identified. Subsequently, each of 6 live horses underwent a bilateral ultrasound-guided stimulation of the FCN at the alar foramen 3 times at 3-week intervals. After each procedure, horses were examined daily for 5 days. RESULTS In each cadaver, the FCN passed through the alar foramen; a communicating branch between the FCN and the accessory nerve and anastomoses between the ventral branches of the FCN and second cervical nerve were identified. The anastomoses were located in the upper third of the FCN pathway between the wing of the atlas and the nerve's entry in the omohyoideus muscle. Successful ultrasound-guided electrical stimulation was confirmed by twitching of the ipsilateral omohyoideus muscle in all 6 live horses; this finding was observed bilaterally during each of the 3 experimental sessions. No complications developed at the site of stimulation. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that ultrasound-guided stimulation of the FCN at the alar foramen appears to be a safe and straightforward procedure in horses. The procedure may have potential for use in horses with naturally occurring recurrent laryngeal neuropathy to assess reinnervation after FCN transplantation or nerve-muscle pedicle implantation in the cricoarytenoideus dorsalis muscle.
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http://dx.doi.org/10.2460/ajvr.77.11.1245DOI Listing
November 2016

Restoration of normal swallowing function in Wallenberg syndrome by repetitive transcranial magnetic stimulation and surgery.

Ann Phys Rehabil Med 2016 Dec 21;59(5-6):343-345. Epub 2016 Jun 21.

EA 38 30, Groupe de recherche sur le handicap ventilatoire, Rouen University, 76031 Rouen, France; Cervicofacial Surgery Department, Rouen University Hospital, 76031 Rouen, France.

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http://dx.doi.org/10.1016/j.rehab.2016.04.008DOI Listing
December 2016

Effect of submental sensitive transcutaneous electrical stimulation on virtual lesions of the oropharyngeal cortex.

Ann Phys Rehabil Med 2016 Apr 21;59(2):94-9. Epub 2015 Dec 21.

Service de physiologie, CHU de Rouen, 1, rue de Germont, 76031 Rouen cedex, France; EA 3830, université de Rouen, 76000 Rouen, France; Pôle 3R, CHU de Rouen, 76031 Rouen, France. Electronic address:

Objective: The aim of this study was to assess the effect of submental sensitive transcutaneous electrical stimulation (SSTES) on pharyngeal cortical representation after the creation of an oropharyngeal cortical virtual lesion in healthy subjects.

Methods: Motor-evoked potential amplitude of the mylohyoid muscles was measured with transcranial magnetic stimulation (TMS), the oropharyngeal cortex was mapped by cartography, and videofluoroscopic parameters of swallowing function were measured before and after SSTES (at the end of SSTES [0 min] and at 30 and 60 min), after the creation of a cortical virtual lesion (repetitive TMS, 1 Hz, 20 min on the dominant swallowing hemisphere).

Results: Nine subjects completed the study. After 20 min of SSTES, motor-evoked potential amplitude increased (P<0.05), as did swallow reaction time after repetitive TMS, as seen on videofluoroscopy, which was reversed after electrical stimulation. On cortical mapping, the number of points with a cortical response increased in the dominant lesioned hemisphere (P<0.05), remaining constant at 60 min (P<0.05).

Conclusion: SSTES may be effective for producing cortical plasticity for mylohyoid muscles and reverses oropharyngeal cortical inhibition in healthy subjects. It could be a simple non-invasive way to treat post-stroke dysphagia.
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http://dx.doi.org/10.1016/j.rehab.2015.10.010DOI Listing
April 2016

Lateral semicircular canal fistula in cholesteatoma: diagnosis and management.

Eur Arch Otorhinolaryngol 2016 Aug 8;273(8):2055-63. Epub 2015 Sep 8.

Otolaryngology-Head and Neck Surgery Department, Rouen University Hospital, Rouen, France.

The objective of this retrospective study was to present the authors' experience on the management of labyrinthine fistula secondary to cholesteatoma. 695 patients, who underwent tympanoplasty for cholesteatoma, in a University Hospital between 1993 and 2013 were reviewed, to select only those with labyrinthine fistulas. 42 patients (6%) had cholesteatoma complicated by fistula of the lateral semicircular canal (LSCC). The following data points were collected: symptoms, pre- and postoperative clinical signs, surgeon, CT scan diagnosis, fistula type, surgical technique, preoperative vestibular function and audiometric outcomes. Most frequent symptoms were unspecific, such as otorrhea, hearing loss and dizziness. However, preoperative high-resolution computed tomography predicted fistula in 88 %. Using the Dornhoffer and Milewski classification, 16 cases (38 %) were identified as stage 1, 22 (52 %) as stage II, and 4 (10 %) as stage III. The choice between open or closed surgical procedure was independent of the type of fistulae. The cholesteatoma matrix was completely removed from the fistula and immediately covered by autogenous material. In eight patients (19 %), the canal was drilled with a diamond burr before sealing with autologous tissue. After surgery, hearing was preserved or improved in 76 % of the patients. There was no statistically significant relationship between the extent of the labyrinthine fistula and the hearing outcome. In conclusion, a complete and nontraumatic removal of the matrix cholesteatoma over the fistula in a one-staged procedure and its sealing with bone dust and fascia temporalis, with sometimes exclusion of the LSCC, is a safe and effective procedure to treat labyrinthine fistula.
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http://dx.doi.org/10.1007/s00405-015-3775-6DOI Listing
August 2016

Newborn hearing screening: analysis and outcomes after 100,000 births in Upper-Normandy French region.

Int J Pediatr Otorhinolaryngol 2015 Jun 23;79(6):829-833. Epub 2015 Mar 23.

Department of Pediatric Ear Nose and Throat and Head and Neck Surgery, Rouen University Hospital (CHU), 1 rue de Germont, 76031 Rouen Cedex, France; Department of Ear Nose and Throat and Head and Neck Surgery, Evreux General Hospital, rue Léon Schwartzenberg, 27015 Evreux Cedex, France.

Objectives: Neonatal hearing impairment is a common disorder with a prevalence of 1 to 2‰ worldwide, with significant consequences on overall development when rehabilitated too late. New-born hearing screening has been implemented in the 1990s in most European countries and the USA. The Upper-Normandy region of France has been conducting a pilot program since 1999. The aim of this prospective study was to evaluate and critically analyse it.

Methods: The Upper-Normandy universal new-born hearing screening program is performed in two steps. Between 1999 and 2004, first, we administered a Transient Evoked Oto Acoustic Emission (TEOAE) test was administered a few days after birth for healthy newborns without risk factors. For newborns admitted to a neonatal intensive care unit (NICU) or presenting risk factors, was administered an automated auditory brainstem response (AABR) test prior to discharge. Second, newborns who failed the initial hearing screening were retested as outpatients using TEOAE. Since 2004, infants who failed the initial screen were tested with AABR 3 to 4 weeks later as outpatients, providing an opportunity to compare the two protocols.

Results: Overall screening coverage in the Upper-Normandy region is 99.8%. First step coverage is 99.58% in well-infant nurseries and 97.09% in the NICU. The test-retest procedure during the first step and the use of AABR for the second resulted in higher follow-up rates and lower false positive rates.

Conclusions: The Upper-Normandy region universal newborn hearing screening program facilitated diagnosis and rehabilitation of infants before age of 9 months, most notably when severe to profound hearing impairment was found.
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http://dx.doi.org/10.1016/j.ijporl.2015.03.012DOI Listing
June 2015

Malignant triton tumour of the sinonasal tract: Case report and literature review.

Int J Surg Case Rep 2014 23;5(9):608-12. Epub 2014 Jul 23.

Department of Otolaryngology, University Hospital of Rouen, France.

Introduction: The objective is to report a rare tumour of the sinonasal tract and conduct a literature review. Malignant triton tumour is a subtype of malignant schwannoma with rhabdomyoblastic differentiation. It is a very rare tumour, with only 15 reported cases involving the sinonasal region.

Presentation Of Case: Forty-seven years old female presented with a right-sided epistaxis, progressive right sided nasal obstruction and anosmia and a visible mass in the right nasal cavity. Imaging studies showed a mass extending from the piriform aperture to the nasopharynx in contact with the dura and the orbital content. The mass was biopsied and the result was consistent with malignant triton tumour. The patient refused the surgery at first so chemotherapy with MAID protocol was started. After the fourth course of chemotherapy the treatment was stopped due to patient intolerance and a thrombosis of the jugular vein. Patient then underwent surgery with frontal craniotomy and dural excision, endoscopic control was done at the end to insure a complete removal. The patient received Radiotherapy in the postoperative period (56 Greys). At 5 years of follow up the patient is doing fine with no signs of recurrence and normal ophthalmological findings.

Discussion: Sixteen cases, including our case, have been reported to date in the literature. The mean age at presentation is 61 years. None of cases were associated with neurofibromatosis type 1. Eight patients were reported to be alive 5 years post-treatment, and 2 patients were reported to have died of the disease. The prognosis for triton tumours in the sinonasal tract is better than that for triton tumours in other locations.

Conclusion: Malignant triton tumour is a rare malignancy of the sinonasal tract. Otolaryngologists should be aware of this disease. The optimal treatment should include radical resection of the tumour.
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http://dx.doi.org/10.1016/j.ijscr.2014.07.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4200876PMC
September 2014

Titanium prosthesis or autologous incus for total ossicular reconstruction in the absence of the stapes suprastructure and presence of mobile footplate.

Eur Arch Otorhinolaryngol 2015 Oct 3;272(10):2653-7. Epub 2014 Aug 3.

Service of Otolaryngology, University Hospital of Rouen, 1 rue germont, 76000, Rouen, France,

The purpose of this study was to compare the hearing results after total ossicular replacement with a titanium prosthesis or autologous incus in the absence of stapes suprastructure and presence of mobile footplate as a retrospective medical record review in a tertiary referral center setting. There were 49 patients who had total ossicular reconstruction (titanium prosthesis, 40 patients; autologous incus, 9 patients). Medical records were reviewed after total ossicular replacement. Air-bone gap at 1 and 2 years after surgery were determined with the 4-frequency average (0.5, 1, 2, and 4 kHz) and the American Academy of Otolaryngology-Head and Neck Surgery 4-frequency average (0.5, 1, 2, and 3 kHz). The number of patients who had air-bone gap <20 dB was determined. For comparisons that were based on American Academy of Otolaryngology-Head and Neck Surgery 4-frequency average, mean air-bone gap at 2 years after surgery was significantly smaller for the titanium prosthesis (21 dB) than autologous incus group (31 dB; P ≤ 0.03); the frequency of patients who had air-bone gap <20 dB at 1 or 2 years after surgery was significantly greater for the titanium prosthesis (1 year, 40%; 2 years, 56%) than autologous incus group [1 year, 0% (P ≤ 0.03); 2 years, 0% (P ≤ 0.04)]. Titanium prosthesis ossiculoplasty gave better results than autologous incus in the absence of the stapes suprastructure and presence of a mobile footplate.
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http://dx.doi.org/10.1007/s00405-014-3212-2DOI Listing
October 2015

Intralabyrinthine schwannomas: a case series with discussion of the diagnosis and management.

Otol Neurotol 2015 Feb;36(2):e64-5

Department of Otolaryngology-Head and Neck Surgery Rouen University Hospital, Rouen, France E-mail:

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http://dx.doi.org/10.1097/MAO.0000000000000397DOI Listing
February 2015

Transplantation of olfactory ensheathing cells to evaluate functional recovery after peripheral nerve injury.

J Vis Exp 2014 Feb 23(84):e50590. Epub 2014 Feb 23.

UPRES EA3830, Institute for Research and Innovation in Biomedicine, University of Rouen; Otorhinolaryngology, Head and Neck Surgery Department, Rouen University Hospital.

Olfactory ensheathing cells (OECs) are neural crest cells which allow growth and regrowth of the primary olfactory neurons. Indeed, the primary olfactory system is characterized by its ability to give rise to new neurons even in adult animals. This particular ability is partly due to the presence of OECs which create a favorable microenvironment for neurogenesis. This property of OECs has been used for cellular transplantation such as in spinal cord injury models. Although the peripheral nervous system has a greater capacity to regenerate after nerve injury than the central nervous system, complete sections induce misrouting during axonal regrowth in particular after facial of laryngeal nerve transection. Specifically, full sectioning of the recurrent laryngeal nerve (RLN) induces aberrant axonal regrowth resulting in synkinesis of the vocal cords. In this specific model, we showed that OECs transplantation efficiently increases axonal regrowth. OECs are constituted of several subpopulations present in both the olfactory mucosa (OM-OECs) and the olfactory bulbs (OB-OECs). We present here a model of cellular transplantation based on the use of these different subpopulations of OECs in a RLN injury model. Using this paradigm, primary cultures of OB-OECs and OM-OECs were transplanted in Matrigel after section and anastomosis of the RLN. Two months after surgery, we evaluated transplanted animals by complementary analyses based on videolaryngoscopy, electromyography (EMG), and histological studies. First, videolaryngoscopy allowed us to evaluate laryngeal functions, in particular muscular cocontractions phenomena. Then, EMG analyses demonstrated richness and synchronization of muscular activities. Finally, histological studies based on toluidine blue staining allowed the quantification of the number and profile of myelinated fibers. All together, we describe here how to isolate, culture, identify and transplant OECs from OM and OB after RLN section-anastomosis and how to evaluate and analyze the efficiency of these transplanted cells on axonal regrowth and laryngeal functions.
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http://dx.doi.org/10.3791/50590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4130567PMC
February 2014

Preoperative computed tomography scan may fail to predict perilymphatic gusher.

Ann Otol Rhinol Laryngol 2013 Jun;122(6):374-7

Department of Otolaryngology-Head and Neck Surgery, Rouen University Hospital-Charles Nicolle, France.

Objectives: A stapes gusher is a very rare event in ear surgery, but the consequences for hearing can be dramatic. It can usually be predicted by characteristic radiologic abnormalities. We report 2 cases of gusher without any abnormalities seen on the preoperative computed tomography scans.

Methods: The first case was in a 30-year-old man with a bilateral mixed hearing loss. The gusher occurred after a stapedotomy performed with a microdrill. The oval window was plugged with a vein graft, and a fluoroplastic piston was inserted. The second case was in a 39-year-old woman with a family history of hearing loss who presented with a bilateral mixed hearing loss. The footplate was fractured during the stapedotomy drilling and was covered with a temporalis fascia graft that was fixed with a fluoroplastic piston.

Results: The first patient had no cerebrospinal fluid leakage and no vertigo or tinnitus. He did have a sensorineural hearing loss. The second patient had dizziness and tinnitus. Postoperative magnetic resonance imaging scans were performed, but again no features were identified that might have predicted these cases.

Conclusions: Surgeons should be reminded that a preoperative computed tomography scan may fail to detect the risk of a perilymphatic gusher.
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http://dx.doi.org/10.1177/000348941312200605DOI Listing
June 2013

Potential of olfactory ensheathing cells from different sources for spinal cord repair.

PLoS One 2013 24;8(4):e62860. Epub 2013 Apr 24.

UPRES EA 3830, Institute for Research and Innovation in Biomedicine, University of Rouen, Rouen, Normandy, France.

Spinal cord injury (SCI) induces a permanent disability in patients. To this day no curative treatment can be proposed to restore lost functions. Therefore, extensive experimental studies have been conducted to induce recovery after SCI. One of the most promising therapies is based on the use of olfactory ensheathing cells (OECs). OECs can be obtained from either the olfactory bulbs (OB-OECs) or from olfactory mucosa (OM-OECs), involving a less invasive approach for autotransplantation. However the vast majority of experimental transplantations have been focusing on OB-OECs although the OM represents a more accessible source of OECs. Importantly, the ability of OM-OECs in comparison to OB-OECs to induce spinal cord recovery in the same lesion paradigm has never been described. We here present data using a multiparametric approach, based on electrophysiological, behavioral, histological and magnetic resonance imaging experiments on the repair potential of OB-OECs and OM-OECs from either primary or purified cultures after a severe model of SCI. Our data demonstrate that transplantation of OECs obtained from OB or OM induces electrophysiological and functional recovery, reduces astrocyte reactivity and glial scar formation and improves axonal regrowth. We also show that the purification step is essential for OM-OECs while not required for OB-OECs. Altogether, our study strongly indicates that transplantation of OECs from OM represents the best benefit/risk ratio according to the safety of access of OM and the results induced by transplantations of OM-OECs. Indeed, purified OM-OECs in addition to induce recovery can integrate and survive up to 60 days into the spinal cord. Therefore, our results provide strong support for these cells as a viable therapy for SCI.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0062860PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3634744PMC
December 2013