Upper airway obstruction assessment: Peak inspiratory flow and clinical COPD Questionnaire.

OBJECTIVES: Spirometric evaluation of upper airway obstruction (UAO) is not commonly performed by Otolaryngologists. In addition, functional evaluation of UAO by flow-volume loops (FVL) is not available in all clinical settings. More recently, peak inspiratory flow (PIF) has proven to be a useful tool to monitor UAO at the patient's bedside. The aim of this work is to assess the role of PIF measured with a simple flow metre (In-Check method) as a standardised, simple, non-invasive tool in quantifying chronic and subacute UAO in a routine clinical practice. In addition, a Clinical COPD Questionnaire (CCQ), previously validated to assess the psychophysical status in patients with laryngotracheal stenosis, was utilised to evaluate respiratory function in UAO. DESIGN: Prospective cohort study. SETTINGS: University teaching hospital. PARTICIPANTS: Seventy 2 subjects, an UAO group of 26 patients and a control group of 46 healthy subjects. MAIN OUTCOME MEASURES: The ability of PIF values to discriminate between the UAO group and the control group was assessed using a ROC curve. A Spearman rank correlation was used to test the relationship between PIF measurements and the global CCQ score. Additionally, an analysis of CCQ at domain and items levels was performed. RESULTS: Peak inspiratory flow values were accurate, with an area under the ROC curve (AUC) of 0.98 (P < .05) for differentiating the control group from the UAO group. A threshold PIF value of 170 L/min was found for diagnosing UAO. An inconclusive negative trend was found (r = -.19; P = .35) between PIF values and CCQ global score. Concerning CCQ, the symptoms domain was the most affected by UAO, higher than mental domains (P < .001) as well as functional domains (P < .01). Exertional dyspnoea and cough were the items that obtained the highest disturbed scores. CONCLUSIONS: Peak inspiratory flow is a non-invasive, quantitative parameter to evaluate the severity of UAO. Testing can be easily performed in a routine clinical setting, with a non-expensive hand-held device, and could help medical follow-up programmes and prevent emergency situations. However, FVL may be necessary for further assessment of UAO diseases. The CCQ confirms that exertional dyspnoea is the main symptom of UAO, but cough remains a common symptom.

A tunable copper-catalyzed multicomponent reaction towards alkaloid-inspired indole/lactam polycycles.

A versatile copper(i)-catalyzed cascade multicomponent reaction strategy between readily available (Z)-3-iodoacrylic acids, terminal alkynes, and primary amines is reported, leading to a great diversity of complex heterocyclic backbones based on biorelevant indole/lactam scaffolds.

How blue lining the recurrent laryngeal nerve can aid in re-operative surgery?

The recurrent laryngeal nerve (RLN), is one of the main structures at risk of injury causing vocal cord paralysis during head and neck surgery, especially during thyroid or parathyroid surgery, central neck dissection and upper oesophageal sphincter surgery. We describe the systematic use of marking of the RLN using non-resorbable blue polypropylene suture after its localisation, just inside its penetration below the cricopharyngeal muscle, to help identify the nerve for cases of re-operative surgery in this area. This specific marking technique could facilitate subsequent preservation of the nerve and reduce nerve injury risk in cases of planned or unexpected future operations, as well as emergency surgery due to postoperative complications. We apply this technique simultaneously with intra-operative laryngeal neuromonitoring. This method is safe and easy to perform.

Hyperparathyroidism in pregnancy and 99mTc-MIBI scintigraphy.

INTRODUCTION: Primary hyperparathyroidism (PHPT) during pregnancy can be responsible for serious maternal and foetal complications and should be treated by elective low-risk, minimally invasive surgery. Preoperative assessment of hyperfunctioning parathyroid glands is classically based on high-resolution neck ultrasound (US) and 99mTc-sestamibi/123I scintigraphy. However, administration of any radiopharmaceutical during pregnancy must be limited and justified and US alone may be sufficient to localize an abnormal parathyroid gland. CASE REPORT: We report the case of a 4-month pregnant woman with severe primary hyperparathyroidism, in whom US failed to localize the abnormal parathyroid gland. 99mTc-sestamibi scintigraphy was performed in preference to 18-fluorocholine (FCH)-PET/CT on the basis of a multidisciplinary decision. As 99mTc-MIBI demonstrated an hyperfunctioning right inferior parathyroid, 123I was not administered. A large right paravertebral parathyroid adenoma was successfully removed, as confirmed by decreased postoperative serum parathyroid hormone and calcium levels. The eutrophic newborn infant was delivered at term, with normal serum calcium and TSH levels. DISCUSSION: In pregnant women with primary hyperparathyroidism, US alone may be sufficient when it localizes the abnormal parathyroid gland, allowing elective low-risk minimally invasive surgery. Otherwise, a multidisciplinary approach is mandatory to select the radiopharmaceutical that can be safely used to identify the hyperfunctioning parathyroid gland with minimal risks for the foetus.

Management of incidental discovery of microscopic squamous cell carcinoma in zones of osteoradionecrosis of the mandible.

OBJECTIVES: Osteoradionecrosis (ORN) of the mandible is a common complication of head and neck radiotherapy and often requires surgical treatment. Squamous cell carcinoma (SCC) can be exceptionally discovered within zones of ORN on histological examination of the operative specimen. The authors discuss the management of these lesions based on a short patient series. MATERIALS AND METHODS: This single-centre retrospective study was based on patients managed between 2012 and 2014 for ORN with incidental discovery of microscopic SCC. RESULTS: Five patients with incidental discovery of microscopic SCC in a zone of ORN of the mandible were included in this study. The mean time to onset of ORN after the end of radiotherapy for locally advanced SCC of the oral cavity or oropharynx was 42 months. Surgical treatment consisted of marginal or segmental mandibulectomy with free flap reconstruction. No recurrence was observed with a mean follow-up of 35 months [24-46]. CONCLUSION: The incidental discovery of microscopic SCC in a zone of ORN of the mandible is a rare event and has not been reported in the literature. Optimal management cannot be reliably defined due to the lack of data in the literature, but the present study supports careful histological examination of ORN specimens. Treatment must be as conservative as possible to avoid excessively invasive surgery.

Conservative three-quarter versus subtotal seven-eighths parathyroidectomy in secondary hyperparathyroidism.

OBJECTIVE: There is at present no consensus concerning surgical techniques for secondary hyperparathyroidism (SHPT) in end-stage renal disease (ESRD). Although both subtotal and total parathyroidectomy provide low rates of recurrence, they may induce hypoparathyroidism, damaging the bone and cardiovascular systems. The aim of our study was to compare 3/4 and 7/8 parathyroidectomy in this population and to discuss the potential benefit of more conservative treatment. STUDY DESIGN: Prospective observational study in a university teaching hospital between 2010 and 2014. METHODS: The study included 34 consecutive ESRD patients with SHPT: 19 underwent 3/4 parathyroidectomy (group A*3/4) and 15 underwent 7/8 parathyroidectomy (group B*7/8). Serum intact 1-84 PTH levels (before and 6 months after surgery) and hospital stay were compared between the two groups. RESULTS: Before surgery, PTH levels were similar between the two groups. At month 6 following surgery, median PTH levels were significantly higher in group A*3/4 than in group B*7/8 (109 versus 24pg/mL, respectively; P<0.0006). Hospital stay was shorter in group A*3/4 (4.79 versus 6.80 days, respectively; P=0.008). Postoperative hypoparathyroidism requiring long-term calcium and 1alpha(OH) D3 treatment was reported in 5% of patients in group A*3/4 and 26% of patients in group B*7/8 (P=0.04). CONCLUSIONS: In this preliminary study, 3/4 conservative parathyroidectomy seemed effective and safe, with less reported morbidity than 7/8 parathyroidectomy, as assessed by lower rates of irreversible hypoparathyroidism and shorter hospital stay. LEVEL OF EVIDENCE: 3b, individual case-control study.

Prospective comparison of FDG and FET PET/CT in patients with head and neck squamous cell carcinoma.

AIM: The clinical usefulness of 2-deoxy-2-[F-18]fluoro-D-glucose-positron emission tomography (FDG-PET) in head and neck squamous cell carcinoma (HNSCC) is now well-documented. However, its sensitivity is greater than its specificity due to false-positive results in inflammatory or infectious lesions, which are frequent in this area, in particular after treatment by surgery and/or radiotherapy. O-2-fluoro-(18F)-ethyl-L-thyrosine (FET) has been reported not to be taken up by such lesions, and a preliminary study indicated that this may be clinically useful in HNSCC. We performed a prospective study to compare the diagnostic performances of FDG and FET PET/CT in the different settings of HNSCC. MATERIALS AND METHODS: Twenty-seven patients (20 men and seven women, aged 48-76, among 30 patients included) and 69 suspected cancer sites are now evaluable on basis of postsurgical histology and/or follow-up greater than 6 months; 15 patients were referred for initial staging and 12 during posttherapy follow-up, a recurrence being suspected in eight of them. FDG and FET PET/CT were performed on two different days, the patient fasting for 6 h, 1 h after injection of 5 MBq/kg of body mass of each radiopharmaceutical. Both PET/CT examinations were blind read more than 6 months after the end of inclusions in a random order for each tracer and with a time interval greater than 1 month between FDG and FET PET/CT blind readings. RESULTS: Overall diagnostic performances, derived from blind reading: FDG PET/CT on a per patient basis: sensitivity 100%, specificity 71%, accuracy 93%; FDG PET/CT on a per site basis: sensitivity 95%, specificity 63%, accuracy 83%; FET PET/CT on a per patient basis: sensitivity 70%, specificity 100%, accuracy 78%; FET PET/CT on a per site basis: sensitivity 64%, specificity 100%, accuracy 78%. At site level, sensitivity was significantly greater with FDG (p<0.02) and specificity with FET (p<0.01). The statistical level of significance was not reached at patient level. CONCLUSION: Although its good specificity was confirmed, FET did not appear to be suited as a first-line PET tracer in HNSCC imaging and cannot replace FDG for staging due to insufficient sensitivity. However, it was useful in a few selected cases to favor a wait and see attitude when a FDG+ FET- focus was discovered in patients referred for systematic FDG PET during follow-up. In contrast, second primary cancers should not be ruled out if FDG was clearly positive in the lungs or the digestive tract.

International consensus (ICON) on comprehensive management of the laryngeal nerves risks during thyroid surgery.

The laryngeal monitoring of the inferior and superior laryngeal nerves, and the vagus nerve, has advanced for last years, in practice of thyroid and parathyroid surgery. Different methods are used, using direct or indirect laryngeal stimulation and also intermittent or continuous nerve registration. At present time, various recommendations of it in the world use are reported, and availability of the tool used remains a limit in some countries. The aim of this Icon during Ifos 2017 was to share knowledge about laryngeal intraoperative nerve monitoring (LIONM) procedures and to evaluate current practices used to improve the quality of thyroid and parathyroid surgery. Benefits of LIONM were discussed with three experts (Pr G. Randolph from Boston, Pr Henning Dralle from Halle in Germany, Pr Hoon Yub KIM from Seoul). All of them have been actively involved in the development and use of laryngeal nerve monitoring during thyroid and parathyroid surgery.

Peak inspiratory flow as predictor for tracheotomy.

OBJECTIVES: Quantitative evaluation of upper airway obstruction cannot be commonly performed under acute dyspnea, especially in head and neck cancer (HNC); the decision whether or not to perform airway control surgery may be difficult to reach. Peak inspiratory flow (PIF) has been previously demonstrated to be a useful tool to decide on decannulation after HNC surgery. The aim of the present study was to assess the role of PIF as a standardized non-invasive tool in quantifying severe inspiratory dyspnea requiring emergency tracheostomy. MATERIALS AND METHODS: A single-center prospective observational pilot study analyzed PIF measurements in 22 patients exhibiting acute dyspnea due to upper airway obstruction. MAIN OUTCOME MEASURES: The decision whether or not to perform tracheotomy was taken prior to PIF measurement. PIF was measured with a hand-held PIF meter (In-Check method), and laryngeal fiberoscopy was then performed. Obstruction severity was defined by PIF values. RESULTS: PIF could be measured prior to tracheotomy (imminent in 21 cases, postponed in 1) in all cases. PIF values below 53.1 L/min (i.e., 18.3% of theoretic value) correlated with necessity for emergency tracheotomy. This threshold is concordant with that previously found for the feasibility of decannulation (60L/min). CONCLUSIONS: PIF is a non-invasive quantitative parameter assessing severity of upper airway obstruction, that may be helpful in decision-making for tracheostomy. Testing is simple, quick and reproducible.

How to release neck dissections: Role of the triangle between the spinal accessory nerve and the internal jugular vein.

The neck dissection technique has been precisely defined. It allows resection of lymph node groups, comprising at least groups IIA, IIB, III and IV according to Robbins' classification for head and neck cancer. Neck dissection is classically performed in an upwards and forwards direction, but the technique can vary according to the site of lymph nodes. The authors describe the central role of dissection of the triangle between the spinal accessory nerve and the internal jugular vein at the beginning of neck dissection in order to facilitate group IIB dissection while avoiding traction on the spinal accessory nerve and to ensure early control of the internal jugular vein superiorly; release of the vein also facilitates subsequent dissection of the thyrolinguofacial trunk and identification of the hypoglossal nerve. This specific dissection and its role has not been previously described in the literature. This triangle constitutes the posterior part of group IIA, but is intimately related anatomically to group IIB dissection.

[Imaging of salivary lithiasis]. / Imagerie des lithiases salivaires.

Lithiasis is the most common disease of salivary glands after mumps. The purpose of this review is to analyze the respective role of the different available imaging techniques for the diagnosis of lithiasis and related complications since the treatment of salivary lithiasis has evolved with the emergence of minimally invasive and non surgical techniques. In spite of its limitations, US represents an excellent first line imaging technique because it is non-invasive and widely available. Non contrast helical CT with multiplanar reconstructions seems to be the gold standard for the diagnosis of lithiasis, especially when small and poorly calcified since these may not be visible on standard radiographs. CT allows accurate characterization of the number and position of lithiasis. MR Sialography is increasingly replacing the more invasive conventional sialography for the non invasive visualization of the ductal system of major salivary glands even though conventional sialography has a higher spatial resolution.

Reduction of Parkinson's-related dysphonia by thyroplasty.

Parkinson's-related dysphonia has a negative impact on the quality of speech by increasing the effects of the associated dysarthria. When this dysphonia is related to vocal fold adduction defect, constituting a real glottic insufficiency, vocal fold medialization can be proposed after failure of intensive voice and speech therapy. Acoustic and aerodynamic voice and speech analysis techniques, perceptual evaluation and estimation of vocal handicap, associated with fiberoptic laryngoscopy were performed to determine the indication for vocal fold medialization in these patients with glottic insufficiency. Vocal fold medialization by Montgomery thyroplasty implant was performed under local anesthesia and neuroanalgesia in two patients with Parkinson's disease presenting a dysphonia refractory to speech therapy. Postoperative evaluation showed improvement of voice quality with an increased number of harmonics and improvement of aerodynamic parameters. Vocal fold medialization by Montgomery thyroplasty implant effectively improved voice quality in these two patients allowing a more effective vocal fold adduction. The reducing of the hypophonia has a positive effect on the quality of oral communication. The medialization thyroplasty technique, under local anesthesia, allows intraoperative control of the voice as well as removal of the implant when necessary.

Incidental cervical metastases from thyroid carcinoma during neck dissection.

OBJECTIVES: To quantify and discuss the prevalence of unsuspected thyroid lymph node metastases discovered in specimens from neck dissection for head and neck squamous cell carcinoma (HNSCC) and discuss the impact on patient management. STUDY DESIGN: Retrospective study between May 2004 and January 2007. SETTING: University hospital. METHODS: Pathological analysis of cervical lymph node dissection performed during surgery for HNSCC in a total of 349 neck dissections in 266 consecutive patients. RESULTS: Twenty-one patients showed metastatic lymph nodes from thyroid cancer (prevalence 7.9%): 13 cases were metastatic from a papillary thyroid carcinoma and 8 cases from a follicular carcinoma. In 5 of the 21 patients, classical dissection was associated to recurrent nerve dissection and unilateral lobectomy; no thyroid carcinoma was found. Thirteen patients received radiotherapy for HNSCC. Follow-up comprised annual ultrasonographic examination of the neck and thyroid in these 21 patients. Total thyroidectomy was decided on in 5, with discovery of 3 micro-papillary thyroid carcinomas, in a single patient (complementary 131I treatment). No thyroid carcinomas were found for the other 4 patients. No patients died from thyroid carcinoma during follow-up (mean: 41 months). CONCLUSION: The prevalence of lymph node metastasis from thyroid carcinoma in cervical lymph node dissection during treatment of HNSCC seems higher (7.9%) than rates reported in the literature (0.3 to 1.6%). This may be due to the histopathological methods employed. Management of patients should be discussed in the light of thyroid ultrasonography and prognosis of HNSCC.

p53 gene status as a predictor of tumor response to induction chemotherapy of patients with locoregionally advanced squamous cell carcinomas of the head and neck.

PURPOSE: To determine whether p53 gene status predicts tumor responses to platinum- and fluorouracil-based induction chemotherapy in locoregionally advanced squamous cell carcinomas of the head and neck. PATIENTS AND METHODS: Tumor responses of 105 patients were measured at the primary tumor site. Objective response and major response were defined by a 50% and 80% reduction in tumor size, respectively. All coding parts of p53 gene were directly sequenced. p53 expression in tumor cells was determined by immunohistochemistry. Human papillomavirus infection was detected by polymerase chain reaction. Odd ratios were adjusted by stepwise logistic regression analysis. RESULTS: p53 mutations, p53 expression, and tumor stage were sufficient to explain the variation in tumor responses to chemotherapy in multivariate models. p53 mutation was the only variable to significantly predict objective response (odds ratio, 0. 23; 95% confidence interval, 0.10 to 0.57; P =.002) and was the strongest predictor of major response (odds ratio, 0.29; 95% confidence interval, 0.11 to 0.74; P =.006). p53 expression (odds ratio, 0.39; 95% confidence interval, 0.16 to 0.98) and tumor stage (odds ratio, 0.31; 95% confidence interval, 0.10 to 0.96) also predicted major response. Specific mutations (contact mutations) accounted for much of the reduction in the risk of major response associated with overall mutations. In complementary analyses, p53 expression was weakly predictive of major response in the subgroup with wild-type p53, and p53 mutations also predicted histologic response. CONCLUSION: p53 gene mutations are strongly associated with a poor risk of both objective and major responses to chemotherapy. Contact mutations are associated with the lowest risk of major response to chemotherapy.

Myoblast transfer therapy: is there any light at the end of the tunnel?

Myoblast transfer therapy (MTT) was proposed in the 70's as a potential treatment for muscular dystrophies, based upon the early results obtained in mdx mice: dystrophin expression was restored in this model by intramuscular injections of normal myoblasts. These results were quickly followed by clinical trials for patients suffering from Duchenne Muscular Dystrophy (DMD) in the early 90's, based mainly upon intramuscular injections of allogenic myoblasts. The clinical benefits obtained from these trials were minimal, if any, and research programs concentrated then on the various pitfalls that hampered these clinical trials, leading to numerous failures. Several causes for these failures were identified in mouse models, including a massive cell death of myoblasts following their injection, adverse events involving the immune system and requiring immunosuppression and the adverse events linked to it, as well as a poor dispersion of the injected cells following their injection. It should be noted that these studies were conducted in mouse models, not taking into account the fundamental differences between mice and men. One of these differences concerns the regulation of proliferation, which is strictly limited by proliferative senescence in humans. Although this list is certainly not exhaustive, new therapeutic venues were then explored, such as the use of stem cells with myogenic potential, which have been described in various populations, including bone marrow, circulating blood or muscle itself. These stem cells presented the main advantage to be available and not exhausted by the numerous cycles of degeneration/regeneration which characterize muscle dystrophies. However, the different stem candidates have shown their limits in terms of efficiency to participate to the regeneration of the host. Another issue was raised by clinical trials involving the injection of autologous myoblasts in infacted hearts, which showed that limited targets could be aimed with autologous myoblasts, as long as enough spared muscle was available. This resulted in a clinical trial for the pharyngeal muscles of patients suffering from Oculo-Pharyngeal Muscular Dystrophy (OPMD). The results of this trial will not be available before 2 years, and a similar procedure is being studied for Fascio-Scapulo-Humeral muscular Dystrophy (FSHD). Concerning muscular dystrophies which leave very few muscles spared, such as DMD, other solutions must be found, which could include exon-skipping for the eligible patients, or even cell therapy using stem cells if some cell candidates with enough efficiency can be found. Recent results concerning mesoangioblasts or circulating AC133+ cells raise some reasonable hope, but still need further confirmations, since we have learned from the past to be cautious concerning a transfer of results from mice to humans.

[Treatments of hereditary hemorrhagic telangiectasia of the nasal mucosa]. / Indications et stratégies thérapeutiques des épistaxis dans la maladie de Rendu Osler.

UNLABELLED: Hereditary Hemorrhagic Telangiectasia is a systemic autosomal dominant disorder involving blood vessels. The most common symptom is recurrent epistaxis. The treatments of these epistaxis are numerous but such treatments are often symptomatic and their effects are often not sustained. Some of these treatments may be complicated by visceral vascular malformations. The aim of this study is to propose a treatment plan for these patients with hierarchical organisation of therapeutic options taking into account of their previous therapy. METHOD: H. Plauchu organized in Paris, december 2002 a meeting with any medical specialists of this disease. They have analysed variety of therapies that have been proposed for epistaxis control in Hereditary Haemorrhagic Télangiectasia. RESULTS: Most common use packing of nasal fossa and then hyperselective embolization of the internal maxillary and facial arteries for severe epistaxis. For chronic epistaxis, best treatment use sclerotics products (Ethibloc) and laser. After discussion, primary embolization could be useful to reduce vascularization of nasal fossa. CONCLUSION: Treatment of epistaxis in Hereditary Haemorrhagic Telangiectasia could increase in few years. Use of an index card of for epistaxis in the disease of Rendu-Osler could help to find treatment of choice.

Oncocytic parathyroid adenoma.

INTRODUCTION: Fine-needle aspiration cytology (FNAC) of thyroid nodules commonly reveals the presence of oncocytic cells (or Hürthle cells) in a follicular neoplasm. Histological examination is necessary to determine the benign or malignant nature of the tumour. However, oncocytic cells are also normally present in the parathyroid glands. CASE REPORT: A thyroid nodule was discovered on thyroid ultrasound in a woman with a history of left partial thyroid lobectomy. Fine-needle aspiration cytology revealed a follicular neoplasm comprising oncocytic cells (Hürthle cells). This woman also presented features of hyperparathyroidism with hypercalcaemia. (123)I/(99m)Tc-sestamibi and (18)F-fluorocholine PET-CT scan revealed increased uptake over the remaining left thyroid lobe. Left lobectomy was completed together with thyroid exploration. Histological examination revealed a parathyroid adenoma in the residual thyroid tissue. Parathyroid hormone levels subsequently returned to normal. DISCUSSION: Cytomorphological similarities are often observed between parathyroid and Hürthle cell thyroid tumours. The parathyroid rather than thyroid nature of the tumour must be strongly suspected preoperatively in the presence of hyperparathyroidism.

Dysphagia in oculopharyngeal muscular dystrophy: a series of 22 French cases.

Twenty-two patients (mean age = 67.9 years) with oculopharyngeal muscular dystrophy (OPMD) were referred for dysphagia from 1987 to January 1995. Six patients had suffered aspiration pneumonia, and three had significantly lost weight, while 19 complained of discomfort during swallowing but without weight loss. Swallowing was assessed by fiberscopy during swallowing (last eight patients), videofluoroscopy (12 cases) and manometry (19 cases). Twelve patients underwent a cricopharyngeal (CP) myotomy: 10 showed improvement, one had a partial improvement, and the procedure failed in one (mean follow-up = 29.6 months). In the other cases, CP myotomy was postponed, refused or contraindicated. Of the 22 patients, three died from OPMD consequences. Factors associated with favorable outcome were adequate residual pharyngeal propulsion and no weight loss. In a majority of cases, CP myotomy constitutes an effective treatment of dysphagia with adequate residual propulsion but does not modify the final prognosis and is contraindicated in cases with pharyngeal aperistalsis.

Variability of disease progression in a family with autosomal recessive CMT associated with a S194X and new R310Q mutation in the GDAP1 gene.

Charcot-Marie-Tooth (CMT) with autosomal recessive (AR) inheritance is a heterogeneous group of inherited motor and sensory neuropathies. Six genes and five additional loci have been identified that are responsible for either demyelinating or axonal forms of the disease. The gene encoding the ganglioside-induced-differentiation-associated protein 1 (GDAP1) has been associated with both demyelinating and axonal phenotypes. We report a detailed clinical, electrophysiological, and genetic study of two siblings from a Moroccan ARCMT family who are compound heterozygotes for the already described S194X and a new R310Q mutation in the GDAP1 gene. The electrophysiological data are compatible with an axonal form of the disease. The phenotype included hoarse voice and paralysis of the diaphragm. This study shows the variability of the phenotype associated with mutations in GDAP1 gene in terms of associated signs and severity.

Innervation of adult human laryngeal muscle fibers.

The innervation of laryngeal muscle fibers was appraised in adult humans. Sixteen intrinsic laryngeal muscles were dissected during the autopsy of 4 adults (41-71 years old). Longitudinal serial frozen sections, 60 microm thick, of the whole muscles were double-stained for cholinesterase activity and axonal visualization. About 945 endplates per muscle were analysed using light microscopy. The neuromuscular junctions were always scattered throughout the whole muscles. Most of the muscle fibers showed a single neuromuscular junction, but multi-innervated fibers were found in all of the muscles. Their number was highest in interarytenoid muscles (21% of all the fibers). The distance between multiple neuromuscular junctions was most frequently less than 150 microm. Two neuromuscular junctions were frequently displayed, opposite one another, particularly in thyroarytenoid muscles, and this unusual feature seems specific for laryngeal muscles. The innervation of all of the muscle fibers was exclusively found to be unineuronal, with multi-innervated fibers being innervated by a single axon. Distal axonal degeneration occurred with aging, resulting in a loss in the number of multi-innervated muscle fibers.