Olfactory stem cells reveal MOCOS as a new player in autism spectrum disorders.

With an onset under the age of 3 years, autism spectrum disorders (ASDs) are now understood as diseases arising from pre- and/or early postnatal brain developmental anomalies and/or early brain insults. To unveil the molecular mechanisms taking place during the misshaping of the developing brain, we chose to study cells that are representative of the very early stages of ontogenesis, namely stem cells. Here we report on MOlybdenum COfactor Sulfurase (MOCOS), an enzyme involved in purine metabolism, as a newly identified player in ASD. We found in adult nasal olfactory stem cells of 11 adults with ASD that MOCOS is downregulated in most of them when compared with 11 age- and gender-matched control adults without any neuropsychiatric disorders. Genetic approaches using in vivo and in vitro engineered models converge to indicate that altered expression of MOCOS results in neurotransmission and synaptic defects. Furthermore, we found that MOCOS misexpression induces increased oxidative-stress sensitivity. Our results demonstrate that altered MOCOS expression is likely to have an impact on neurodevelopment and neurotransmission, and may explain comorbid conditions, including gastrointestinal disorders. We anticipate our discovery to be a fresh starting point for the study on the roles of MOCOS in brain development and its functional implications in ASD clinical symptoms. Moreover, our study suggests the possible development of new diagnostic tests based on MOCOS expression, and paves the way for drug screening targeting MOCOS and/or the purine metabolism to ultimately develop novel treatments in ASD.

Safety and effectiveness of the Bonebridge transcutaneous active direct-drive bone-conduction hearing implant at 1-year device use.

The objective of this study is to evaluate the safety and efficacy of a new transcutaneous bone-conduction implant (BCI BB) in patients with conductive and mixed hearing loss or with single-sided deafness (SSD), 1 year after surgical implantation. The study design is multicentric prospective, intra-subject measurements. Each subject is his/her own control. The setting is nine university hospitals: 7 French and 2 Belgian. Sixteen subjects with conductive or mixed hearing loss with bone-conduction hearing thresholds under the upper limit of 45 dB HL for each frequency from 500 to 4000 Hz, and 12 subjects with SSD (contralateral hearing within normal range) were enrolled in the study. All subjects were older than 18 years. The intervention is rehabilitative. The main outcome measure is the evaluation of skin safety, audiological measurements, benefit, and satisfaction questionnaires with a 1-year follow up. Skin safety was rated as good or very good. For the mixed or conductive hearing loss groups, the average functional gain (at 500 Hz, 1, 2, 4 kHz) was 26.1 dB HL (SD 13.7), and mean percentage of speech recognition in quiet at 65 dB was 95 % (vs 74 % unaided). In 5/6 SSD subjects, values of SRT in noise were lower with BB. Questionnaires revealed patient benefit and satisfaction. The transcutaneous BCI is very well tolerated at 1-year follow up, improves audiometric thresholds and intelligibility for speech in quiet and noise, and gives satisfaction to both patients with mixed and conductive hearing loss and patients with SSD.

Switching from a percutaneous to a transcutaneous bone anchored hearing system: the utility of the fascia temporalis superficialis pedicled flap in case of skin intolerance.

OBJECTIVES: To present the option to use a Fascia Temporalis Superficialis pedicled flap for the implantation of a transcutaneous magnetic osseointegrated auditory implant in selected revision procedures. BACKGROUND: Osseointegrated auditory implants represent a reliable option for patients. Skin intolerance and aesthetic issue are two clear limitations of percutaneous system. Magnetic transcutaneous devices have been developed to overcome such drawbacks. The current new experience of such a device shows that they are well tolerated in primary cases. However, switching from a previous percutaneous system raises the question of skin tolerance. Hence, previous implanted abutments with skin penetration and skin reduction are more likely cause to skin intolerance and complication. METHODS: We described here the option to use a Fascia Temporalis Superficialis flap to cover the implanted magnet. CONCLUSION: When switching from percutaneous osseointegrated auditory implant to transcutaneous system in case of high risk of skin intolerance, this procedure may provide sufficient tissue coverage to prevent skin intolerance, pain and delayed extrusion.

[Middle ear barotraumas due to rhinopharyngeal scar tissue: tubomanometry diagnostic and therapeutic contribution]. / Barotraumatismes de l'oreille moyenne par brides rhinopharyngées: intérêt diagnostique et thérapeutique de la tubomanométrie.

OBJECTIVE: Evaluation of tubomanometry contribution to diagnosis middle ear barotraumas in relation with rhinopharyngeal scar tissue, and contribution to check postoperative effectiveness of scar tissue surgical resection. METHODS: Clinical cases study of two stewardesses who have lost their flight fitness consecutively to barotraumatic otitis during landing, engendered by rhinopharyngeal scar tissue. RESULTS: Pre-operative tubomanometric parameters were abnormal in both cases: decrease of intratympanic pressure in one case, variability of tube opening latency index and lengthening of intratympanic pressure rising time in the other case. Surgical section during endonasal endoscopy results in initially abnormal tubomanometric parameters normalization, allowing resumption of flight fitness without any barotrauma. CONCLUSION: Some abnormal tubomanometric parameters help to establish causality link between middle ear barotrauma and rhinopharyngeal scar tissue for which surgical section is thus indicated. Post-operative tubomanometric parameters normalization prove surgical effectiveness. Then, flight fitness could then be restored.

Transoral surgical treatment of Eagle's syndrome: case report and review of literature.

Eagle's syndrome is a symptomatic abnormal length of the styloid process and/or a calcification of the stylohyoid ligament. Diagnosis is based on common pharyngeal symptoms and is confirmed by radiologic examination, more particularly CT-scan. Medical and surgical treatments are described. Medical treatment consists in repeated local anaesthetics, steroid infiltration or analgesics administration. It is purely symptomatic and has no long-term effectiveness. Surgical treatment remains the treatment of choice and consists of removal of the abnormal process. Both transoral and external approaches have been described. The advantages of the transoral approach is a shorter operative time, the absence of aesthetic prejudice and a lesser risk of neurovascular injury. Few post operative complications have been described (surgical cervical emphysema, cervical swelling, trismus and moderate breathing difficulty) but none of the studies reported neurovascular injury, deep cervical infection nor long-term complication. We present the technique, a case report and a review of the literature of the transoral approach.

Comparison of [¹¹¹In]pentetreotide-SPECT and [¹8F]FDOPA-PET in the localization of extra-adrenal paragangliomas: the case for a patient-tailored use of nuclear imaging modalities.

AIMS AND METHODS: The aim of this prospective study was to compare the diagnostic value of [¹8F]FDOPA-PET and [¹¹¹In]pentetreotide-SPECT somatostatin receptor scintigraphy (SRS) in patients with nonmetastatic extra-adrenal paragangliomas (PGLs). Twenty-five consecutive unrelated patients who were known or suspected of having nonmetastatic extra-adrenal PGLs were prospectively evaluated with SRS and [¹8F]FDOPA-PET. ¹³¹I-MIBG and [¹8F]FDG-PET were added to the work-up in patients with a personal or familial history of PGL, predisposing mutations, abdominal PGLs, metanephrine hypersecretion and abdominal foci on SRS and/or [¹8F]FDOPA-PET. RESULTS: SRS correctly detected 23/45 lesions of which 20 were head or neck lesions (H&N) and 3 were abdominal lesions. [¹8F]FDOPA-PET detected significantly more lesions than SRS (39/45, P < 0·001). Both SRS and ¹8F-DOPA-PET detected significantly more H&N than abdominal lesions (66·7% vs 20%, P = 0·003 and 96·7% vs 67%, P = 0·012, respectively). In two patients with the succinate dehydrogenase D (SDHD) mutation, [¹8F]FDOPA-PET missed five abdominal PGLs which were detected by the combination of SRS, [¹³¹I]MIBG and [¹8F]FDG-PET. A lesion-based analysis using a forward stepwise logistic regression model demonstrates that size ≤ 10 mm (P = 0·002) and abdominal lesions (P = 0·031) were independently associated with "[¹8F]FDOPA-PET diagnosis only". In turn, a previous history of surgery and/or the presence of germline mutation was associated with lower lesion size (P = 0·001). CONCLUSIONS: The sensitivity of SRS for localizing parasympathetic PGLs is lower than originally reported, and [¹8F]FDOPA-PET is better than SRS for localizing small lesions. SRS should be replaced by [¹8F]FDOPA-PET as the first-line imaging procedure in H&N PGL, especially in patients at risk of multifocal disease (predisposing mutations and or previous history of surgery).

[An unusual fester of the peri-auricular area: pathomimia in ENT practice]. / A propos d'une ulcération péri-auriculaire atypique: la pathomimie en pratique ORL.

We report a case of a patient who self-injured her ear and peri-auricular skin. Self-mutilation is an unusual behaviour in ENT practice. We give some elements for the diagnosis and treatment, and we emphasize the importance of the psychiatric treatment. The suicidal risk makes the vital prognosis uncertain.

[Paraganglioma of the cerebellopontine angle: report of two cases]. / Paragangliomes de l'angle ponto-cérébelleux: à propos de deux cas.

Paragangliomas of the cerebellopontine angle are exceptional tumours. We report two cases of paragangliomas of the cerebellopontine angle. To our knowledge, including these two cases, only five cases have been reported in the international literature. The emerging field of genetic study of these tumours will prove critical for their diagnosis and prognosis. The presence of paraganglioma in this area is explained by an abnormal embryologic migration of paraganglionic cells into the cerebellopontine angle, associated with tumorogenesis. These tumors can be associated with others cervico-facial tumours and to genomic abnormalities. The preoperative diagnosis of these tumours is very difficult, with clinical signs like hearing loss, vertigo and tinnitus are very ambiguous. Radiologic assessment of the cerebellopontine angle is also vague. The final diagnosis is only made possible peroperatively and by the post-operative histopathologic study. ENT and neurosurgeons should be awarded of the possible existence of paragangliomas of the cerebellopontine angle, and the necessity of a systemic and genetic assessment.

Post-traumatic balance disorder.

The causes of balance disorder are many and various, and the subjective syndrome of cranial trauma patients is diagnosed by elimination. Progress in otoneurologic functional exploration and brain imaging, however, now generally allow this functional complaint to be given an objective basis. In recent years, new diagnoses have improved recognition of such pathologies in the appraisal of corporal injury for compensation purposes. The present article seeks to detail etiology and, by a review of the literature, to determine factors liable to influence management and appraisal in particular.

[Contribution of 18FDG PET/CT post treatment surveillance of head and neck squamous cell carcinoma]. / Intérêt de la TEP au 18FDG couplée à la TDM dans la surveillance post-thérapeutique des carcinomes épidermoïdes des voies aérodigestives supérieures.

OBJECTIVE: To evaluate the contribution of 18FDG positron emission tomography for the post treatment surveillance of head and neck carcinomas. METHODS: : This prospective study included 61 patients with advanced squamous cell carcinoma of the upper airways and/or digestive tract and who underwent curative treatment. Patients underwent a standard workup (physical examination, CT scan and panendoscopy) and a PET/CT image fusion 3 months after the end of treatment. The follow-up was 6 months minimum in all patients after this workup. PET/CT was evaluated in terms of: primary tumor, cervical lymph nodes, metastases and overall patient assessment. RESULTS: : For diagnosis of the primary tumor, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of PET/CT were respectively 86.7%, 82.6%, 62%, 95% and 83.6%. Values for cervical lymph nodes were: 100%, 98.2%, 80%, 100% and 98.3%. Values for metastases were: 100%, 92.2%, 66.7%, 100% and 93.2%. Values for overall patient assessment were: 88.8%, 78.1%, 64%, 94.1% and 81.4%. Performances of PET/CT were better than standard workup in 22% of patients. CONCLUSION: PET/CT contributes useful information in this indication, particularly an excellent negative predictive value.

[Facial paralysis: functional and aesthetic rehabilitation techniques]. / Réhabilitation fonctionnelle et esthétique de la face paralysée.

The diagnosis of a permanent facial paralysis can be devastating to a patient, because of the cosmetic, functional and psychological disorders. Our society places on physical appearance and leads to isolation of patients who are embarrassed with their paralyzed face. The objectives of the facial rehabilitation is to correct the functional and cosmetic losses of the patient. The main functional goals are to protect the eye and reestablish oral competence. The primary cosmetic goals are to create balance and symmetry of the face at rest and to reestablish the coordinated movement of the facial musculature. The surgeon should be familiar with the variety of options available so that an individual plan can be developed based on each patient's clinical picture. History of the facial paralysis, its etiology and the duration of the paralysis are of particular interest as they orientate the rehabilitation plan strategy.

Treatment of a mastoid defect by free anterolateral thigh flap.

INTRODUCTION: Free anterolateral thigh (ALT) flap constitutes an alternative to latissimus dorsi and radial forearm flaps for head and neck reconstruction. The authors report a case of mastoid reconstruction in a patient with multi-operated cholesteatoma associated with tubal dysfunction. CASE REPORT: This patient presented a fistula of the lateral semicircular canal and invagination of retroauricular soft tissues responsible for non-compensated almost complete areflexia with anacusis. She did not present any signs of cholesteatoma recurrence, but chronic inflammation of the mastoidectomy cavity. The head and neck procedure consisted of translabyrinthine labyrinthectomy: resection of the atrophic retroauricular skin, resection of the vestibular neurosensory tissue and obliteration of the mastoidectomy cavity. An ALT flap measuring 5×5 cm, anastomosed to the superior thyroid artery and facial vein, was used to cover the defect. Careful defatting of the flap allowed filling of the defect, while providing a sufficient quantity of appropriate tissue. The postoperative course was uneventful and the patient was considerably improved. The only donor site sequelae consisted of a thin linear scar. CONCLUSION: The free anterolateral thigh flap, a reliable, polyvalent flap that can be shaped as needed and which is associated with minimal donor site morbidity, constitutes a good alternative for head and neck reconstruction.

Cavernous sinus thrombosis secondary to non-invasive sphenoid aspergillosis.

The sphenoid localization of aspergillosis is a rare sinusal disease, often latent or asymptomatic. The neurological complications are the result of invasive forms occurring in most cases for the immunocompromised or diabetic patients. Nevertheless, non-invasive sphenoid aspergillosis may cause also several complications and affect the vital prognosis of nonimmunocompromised patients. This report is about two cases of cavernous sinus thrombosis secondary to a non-invasive sphenoid aspergillosis. The authors refer to the clinical and radiological findings and therapeutic approach of this rare complication.

Mini-invasive surgery of infratemporal fossa schwannomas.

BACKGROUND: Infratemporal fossa schwannomas are benign, encapsulated tumours of the trigeminal nerve limited to the infratemporal fossa. Because of the complications and significant morbidity associated with traditional surgical approaches to the infratemporal fossa, which include facial nerve dysfunction, hearing loss, dental malocclusion and cosmetic problems, less invasive alternatives have been sought. METHODS: This paper reports two cases of infratemporal fossa schwannomas treated in 2012 using mini-invasive approaches. The literature regarding different infratemporal fossa approaches was reviewed. RESULTS: The first schwannoma was 30 mm in size and was removed completely by a preauricular subtemporal approach. The second one was 25 mm in size and was removed completely using a purely transnasal endoscopic approach. In both cases, there were no intra-operative or post-operative complications. CONCLUSION: These two approaches allow non-invasive and wide exposure of the infratemporal fossa as compared to classical approaches. Surgical approach should be selected according to the tumour's anatomical location with respect to the maxillary sinus posterior wall. The preauricular subtemporal approach is recommended for tumours localised posterolaterally with respect to the maxillary sinus posterior wall. Medial and anterior tumours near the maxillary sinus posterior wall can be best removed using a transnasal endoscopic approach.

Vestibular compensation following vestibular neurotomy.

OBJECTIVES: Four studies assessing vestibular compensation in Menière's disease patients undergoing unilateral vestibular neurotomy, using different analysis methods, are reviewed, with a focus on the different strategies used by patients according to their preoperative sensory preference. MATERIAL AND METHODS: Four prospective studies performed in a university tertiary referral center were reviewed, measuring the pattern of vestibular compensation in Menière's disease patients before and after unilateral vestibular neurotomy on various assessment protocols: postural syndrome assessed on static posturography and gait analysis; perceptual syndrome assessed on subjective visual vertical perception; and oculomotor syndrome assessed on ocular cyclotorsion. RESULTS: Vestibular compensation occurred at variable intervals depending on the parameter investigated. Open-eye postural control and gait/walking returned to normal one month after neurotomy. Fine balance analysis found that visual perception of the vertical and ocular cyclotorsion impairment persisted at long-term follow-up. Clinical postural disturbance persisted only when visual afferents were cut off (eyes closed). These impairments were the expression of a postoperative change in postural strategy related to the new use of visual and non-visual references. CONCLUSIONS: Understanding pre-operative interindividual variation in balance strategy is critical to screening for postural instability and tailoring vestibular rehabilitation.

Effects of haptic supplementation on postural stability in unilateral vestibular loss patients.

The effects of haptic supplementation on postural stability during upright standing with vision were investigated in 11 unilateral vestibular loss (UVL) patients and compared to 12 age-marched controls. All the participants were instructed to grip a fixed or mobile stick. In the mobile conditions, the lower extremity of the stick was in contact with a slippery or a rough surface. Postural stability was assessed by the root mean square (RMS) and the velocity of the center of foot pressure (CoP) displacements in both antero-posterior (AP) and medio-lateral (ML) directions. Results showed that RMS was larger in UVL patients than in aged-matched participants in AP direction. However, in the mobile stick conditions, only the rough surface improved postural stability. In addition, RMS was more sensitive to haptic supplementation than CoP velocity. The present study confirms the importance of haptic information in the multi-sensory (re) weighting process underlying postural control in UVL patients.

Indications and results of video-assisted parathyroidectomy by a lateral approach in patients with primary hyperparathyroidism.

BACKGROUND: Different minimally invasive techniques of parathyroidectomy have been described. We performed a retrospective study to evaluate the indications and results of video-assisted parathyroidectomy by lateral approach (VAPLA) in the management of our patients with primary hyperparathyroidism (PHPT). METHODS: From December 1997 to December 2000, we operated on 293 patients with PHPT. VAPLA was proposed for patients with sporadic PHPT in whom a single adenoma was localized by means of sonography or sestamibi scanning, or both. VAPLA was performed on the anterior border of the sternocleidomastoid muscle. A quick parathormone (PTH) assay was used during the surgical procedures. RESULTS: Of the 293 patients, 127 (43.3%) were not eligible for VAPLA: ipsilateral previous neck surgery (28 cases), associated nodular goiter (59 cases), suspicion of multiglandular disease (15 cases), no preoperative localization (17 cases), and miscellaneous causes (8 cases). VAPLA was performed in 166 patients (56.7%). Conversion to conventional parathyroidectomy was required in 26 patients (15.6%). Morbidity included 2 local hematomas, 1 definitive recurrent nerve palsy, and 4 capsular fractures. All of the 166 patients were normocalcemic, with follow-up ranging from 3 to 33 months. CONCLUSIONS: VAPLA is safe and effective. It should be reserved for patients with sporadic PHPT, with a small single adenoma clearly localized preoperatively.

[Thyrotoxic hypokalemic periodic paralysis. Report of three cases]. / La paralysie périodique thyréotoxique hypokaliémique. Présentation de trois cas.

AIM OF THIS STUDY: Hypokaliemic thyrotoxic periodic paralysis (HTPP) is an uncommon complication of hypothyroidism. Mostly described among Asian patients, it is rare in the other ethnic groups, in particular in caucasians people. Among the possible mechanisms, modification of potassic flows in relation to anomalies of the sodium-potassium pump were evoked. PATIENTS AND METHOD: We present the cases of three caucasians patients operated on for HTPP. These patients had all previous history of several paretic episodes. The flask paralytic attacks occurred in a brutal way or were preceded by diffuse myalgias. They reached the proximal muscles, especially in inferior limbs. No patient had any respiratory complications. These three patients underwent total thyroidectomy to treat the symptoms of HTPP. RESULTS: In the three cases, a total thyroidectomy allowed the recovery of the symptoms. After a four years average period of post-operative follow-up, no patient presented any repetition of HTPP. The hyperthyroidism is the cause of decompensation of the molecular anomaly. CONCLUSION: In our opinion, surgical treatment (total thyroidectomy) is needed in order to reduce the potential gravity of this pathology.

[Functional outcomes after translabyrinthine approach for vestibular schwannomas]. / Résultats de l'exérèse par voie translabyrinthique élargie des schwannomes vestibulaires.

PURPOSE: The aim of this paper is to present the functional outcomes after translabyrinthine approach (TLA) for vestibular schwannoma (VS). We analyzed data from 95 patients who had undergone surgery on between 1991 and 2001. METHODS: This retrospective study of clinical and radiological data concerned 95 patients operated on by TLA for a unilateral vestibular schwannoma, excluding NF2 patients and those who have been operated on after a gamma-knife treatment. Results were evaluated with at least 2 Years follow-up and compared with recent data in the literature. RESULTS: Complete tumor removal was achieved in 84% of cases. The facial nerve was normal at the end of the operative procedure in 85%. Facial nerve function was evaluated in 90 patients with two Years follow-up: 62% were grade I or II according to the House and Brackmann scale, 21% were grade III and 16.5% grade IV to VI. CSF leakage was noted in 8.4% including rhinorrhea in 4.2%. No deaths occurred during this period. CONCLUSION: The results related here show that TLA is a safe and efficient procedure for the removal of large acoustic neuromas.

[Results and indications of gamma knife radiosurgery for large vestibular schwannomas]. / Résultats et indications de la radiochirurgie Gamma Knife des schwannomes vestibulaires de gros volume.

Regular treatment of large vestibular schwannomas (VS) is surgical resection of the tumor with attempt of facial nerve preservation. In a very reduced number of tumors, microsurgery is not warranted mainly because of controlateral deafness or the risk of life-threatening open surgery. The purpose of this study was to analyze the results of Gamma Knife radiosurgery delivered for large VS. Between July 1992 and January 2002, we treated 50 patients harboring a large VS defined as a Koos grade IV tumor. Data and follow-up were available for 45 tumors involving 44 patients, including 12 neurofibromatosis type 2. Mean age at the time of treatment was 43,5 (range: 14-84), mean diameter of the tumor in the CPA was 18mm (range: 12-30) and the mean Volume was 4301 mm3 (range: 1340-11405). Gamma knife treatment was undertaken using on average 13.4 isocenters (range: 4-48) and 10.2 Gy at the tumor margin (range: 8-14). Median follow-up was 45.5 Months (from 24 to 108 Months). Tumor control was 69% (interval confidence: 52-83%) and 3 patients had to be operated because of continuous tumor growth. Statistical analysis showed that tumor Volume was correlated to Gamma Knife failure in a uni-and multivariate model (p=0.027). No brain stem complication was observed. No facial nerve deterioration was found and hearing preservation could be obtained at a useful level in 12 out of 20 patients (60%). These results suggest that in a highly selected subgroup of patients with large VS, radiosurgery can be an interesting alternative to open surgery, particularly if hearing preservation is required. Information should be given to the patients that the risk of failure is greater than for small and medium sized VS.