Rare Missense Variants in KCNJ10 Are Associated with Paroxysmal Kinesigenic Dyskinesia.

BACKGROUND: Although the group of paroxysmal kinesigenic dyskinesia (PKD) genes is expanding, the molecular cause remains elusive in more than 50% of cases. OBJECTIVE: The aim is to identify the missing genetic causes of PKD. METHODS: Phenotypic characterization, whole exome sequencing and association test were performed among 53 PKD cases. RESULTS: We identified four causative variants in KCNJ10, already associated with EAST syndrome (epilepsy, cerebellar ataxia, sensorineural hearing impairment and renal tubulopathy). Homozygous p.(Ile209Thr) variant was found in two brothers from a single autosomal recessive PKD family, whereas heterozygous p.(Cys294Tyr) and p.(Thr178Ile) variants were found in six patients from two autosomal dominant PKD families. Heterozygous p.(Arg180His) variant was identified in one additional sporadic PKD case. Compared to the Genome Aggregation Database v2.1.1, our PKD cohort was significantly enriched in both rare heterozygous (odds ratio, 21.6; P = 9.7 × 10-8) and rare homozygous (odds ratio, 2047; P = 1.65 × 10-6) missense variants in KCNJ10. CONCLUSIONS: We demonstrated that both rare monoallelic and biallelic missense variants in KCNJ10 are associated with PKD. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Sinonasal and ear manifestations of Erdheim-Chester disease.

To calculate the prevalence of sinonasal and ear involvement in an Erdheim-Chester disease (ECD) population, to describe the different ear, nose and throat (ENT) manifestations and to study the association between ENT involvement, other organ involvement, and BRAF mutations. We led a retrospective monocentric study in the national referral center for ECD. One hundred and sixty-two patients with ECD and ENT data were included between January 1, 1980 and December 31, 2020. Ear and nose clinical and radiological findings were noted. We described and studied the prevalence of ENT involvement in ECD population. The association between sinonasal and ear involvement, other organ involvement, and BRAF mutations was calculated. The prevalence of ENT manifestations is around 45%. No clinical rhinologic or otologic signs were specific to ECD. Sinus imaging was abnormal in 70% of cases. A bilateral maxillary sinus frame osteosclerosis was highly specific of ECD. Associations were found between the sinus MRI imaging type and BRAF status, central nervous system involvement, cerebellum involvement and xanthelasma. Sinonasal or ear involvement is frequent in ECD and has specific imaging features for sinuses. Trial registration: #2011-A00447-34.

Cochlear implantation and facial nerve anastomosis to rehabilitate a burnt middle ear.

A 48-year-old man presented to the ENT department of a general hospital after a traumatic event that occurred at work. During arc welding, an incandescent metallic projectile entered the left external auditory canal immediately causing earache, tinnitus, hearing loss, vertigo, and completed peripheral facial palsy on the left side. A burnt middle ear is a rare situation for which very few cases are described in the literature. We describe and discuss our therapeutic strategy in an emergency setting. This can be of interest to any ENT surgeon who may face such a case of ear burn. Then we report the first repair of the facial nerve by interposition of an anastomosed intermediate graft associated with cochlear implantation during a single surgical intervention. This case illustrates the multimodal rehabilitation of the damage that can be a consequence of petrous trauma. The patient recovered hearing and facial motor skills.

Outcomes and prognostic factors of facial nerve repair: a retrospective comparative study of 31 patients and literature review.

PURPOSE: To evaluate functional results of facial nerve repair by direct nerve suture or grafting, compare results between a traumatic and a tumoral group and identify prognostic factors. METHODS: A retrospective monocentric cohort study was studied in a university ENT department. Thirty-one patients who benefited from facial nerve suture or grafting, with at least 12 months postoperative follow-up were included. Patients were divided into two groups according to the lesion type: traumatic (accident of the public road or iatrogenic) and tumoral. Preoperative data studied were sex, side, etiology documented by CT and/or MRI, facial palsy duration and grade according to House Brackmann grading system. Intraoperative data included: surgeon, age of patient, surgical technique, graft type, use of biological glue, facial nerve derivation, lesioned site. Postoperative data included: histological diagnosis, radiotherapy history, time to onset of the first signs of reinnervation, follow-up duration, and final facial function. RESULTS: Success rate, including grade III and IV, was 68% in the whole cohort, 79% in the traumatic group and 59% in the tumoral group. Patients presenting with facial palsy evolving less than 6 months had better recovery results than those evolving longer than 6 months (p = 0.02). No other prognostic factors were identified. CONCLUSIONS: The best outcome that can be achieved by suture or grafting of the facial nerve in traumatic or tumoral lesions is a grade III. Preoperative facial palsy duration is a prognostic factor and must be considered when establishing an operative indication.

Oro-facial motor assessment: validation of the MBLF protocol in facial palsy.

BACKGROUND: Oro-facial myofunctional praxis assesses the muscular coordination and the degree of motor impairment of the lingual, mandibular and facial muscles necessary for articulation, mimicry and swallowing. PURPOSE: The objective of this study was to create and validate the MBLF protocol, a French oro-facial myofunctional assessment in order to quantify patient's impairment and to specify the motor and functional deficit for an adapted management. METHODS: The MBLF was validated against the Sunnybrook Facial Grading System (criterion validity). The construct validity was tested by comparing healthy subjects (n = 102) from patients with facial palsy (n = 60). Internal and external consistency of face symmetry were reported. Normative data was provided. RESULTS: There was a statistically significant correlation between the MBLF protocol and the Sunnybrook Facial Grading System [F(59) = 310.51, p < 0.001, R2 = 0.843]. Significant differences were observed in Student's t test between healthy volunteers and patients with facial palsy [t(74.13) = 14,704, p < 0.001, r = 0.863]. A significant effect of the severity grades of facial palsy on the MBLF_TOTAL scores was found [F(158) = 268.469, p < 0.001]. The more severe the facial palsy, the lower the motor scores were. CONCLUSION: This MBLF French validation provides a baseline for comparing and quantifying the performance of subjects. The MBLF protocol is valid for assessing facial symmetry in peripheral facial palsy. A prospective study is needed to validate its role in dynamic evaluation of facial palsy.

Post-COVID-19 Kawasaki-Like Syndrome.

A 42-year-old man was referred for a week history of severe dysphagia, odynophagia, fever (39 °C), fatigue, abdominal pain, pharyngeal swelling, and multiple neck lymphadenopathies. The medical history reported a mild form of COVID-19 one month ago. The biology reported an unspecified inflammatory syndrome. The patient developed peritonitis, myocarditis, and hepatitis. A myocardium biopsy was performed. A diagnosis of Kawasaki-like disease (KLD) was performed. The occurrence of KLD in adults is rare but has to be known by otolaryngologists regarding the otolaryngological clinical presentation that may precede the multiple organ failure.

"Neuro-Fiber Mapping": An Original Concept of Spinal Cord Neural Network Spatial Targeting Using Live Electrostimulation Mapping to (Re-)Explore the Conus Medullaris Anatomy.

Spinal cord (SC) anatomy is often assimilated to a morphologically encapsulated neural entity, but its functional anatomy remains only partially understood. We hypothesized that it could be possible to re-explore SC neural networks by performing live electrostimulation mapping, based on "super-selective" spinal cord stimulation (SCS), originally designed as a therapeutical tool to address chronic refractory pain. As a starting point, we initiated a systematic SCS lead programming approach using live electrostimulation mapping on a chronic refractory perineal pain patient, previously implanted with multicolumn SCS at the level of the conus medullaris (T12-L1). It appeared possible to (re-)explore the classical anatomy of the conus medullaris using statistical correlations of paresthesia coverage mappings, resulting from 165 different electrical configurations tested. We highlighted that sacral dermatomes were not only located more medially but also deeper than lumbar dermatomes at the level of the conus medullaris, in contrast with classical anatomical descriptions of SC somatotopical organization. As we were finally able to find a morphofunctional description of "Philippe-Gombault's triangle" in 19th-century historical textbooks of neuroanatomy, remarkably matching these conclusions, the concept of "neuro-fiber mapping" was introduced.

Comprehensive management of paranasal sinus fungus balls: A Young-IFOS consensus statement.

BACKGROUND: Paranasal sinus fungus balls (PSFB) are a common form of surgically treatable, noninvasive mycosis. To date, no guidelines have standardized PSFB treatment or management of difficult cases (eg, immunocompromised or fragile patients). The clinical consensus statement presented herein aims to provide a comprehensive management guide to PSFB based on current evidence. METHODS: A multidisciplinary, international panel of 19 specialists judged statements in 3 rounds of a modified Delphi method survey. Statements encompassed the following PSFB management issues: definition, diagnostic workup; treatment indications and modalities; and follow-up. Otolaryngologists, maxillofacial surgeons, infectious disease specialists, and transplant physicians were considered the target audience. RESULTS: Among the 23 statements, 7 reached strong consensus and 16 reached consensus. Consensus was reached on the definition, diagnosis, and treatment modalities for PSFB. Postoperative follow-up modalities and scenarios with bacterial superinfection were the most debated issues. CONCLUSION: Until further data are available, these points provide a framework for the management of PSFB. Moreover, PSFB should be considered a noninvasive mycosis that is not necessarily symptomatic or related to odontogenic conditions. Although diagnosis may be incidental, endoscopy and single imaging (computed tomography or magnetic resonance imaging, with distinctive features) are required for diagnosis, whereas contrast medium would allow for differential diagnosis. Although treatment of PSFB should be considered mandatory before sinus augmentation and is recommended for symptomatic patients, immunosuppressed patients, or patients with planned immunosuppression, watchful waiting could be considered for asymptomatic patients with chronic rhinosinusitis who are provided with appropriate advice and assessment.

Pain in Patients with Post Paralytic Hemifacial Spasm: Before, during and after Botulinum Toxin Injections.

It is well-established that botulinum toxin (BT) injections improve quality of life in patients with postparalytic hemifacial spasm. Nevertheless, injection-related pain and contracture-related pain have not yet been studied. The primary objective of our study was to evaluate injection-related pain in patients with facial palsy sequelae, and to compare the standard technique (syringe) with the Juvapen device. The secondary objective was to evaluate the improvement of contracture-related pain one month after BT injection. METHODS: We conducted an observational, prospective, monocentric study based on 60 patients with facial palsy sequelae who received BT injections in our university ENT (ear, nose throat) department. There were 30 patients in the Juvapen group (J) and 30 in the standard technique group (ST). All patients completed Numerical Rating Scale (NRS) questionnaires immediately after the injections and one month later. RESULTS: The average NRS score was 1.33/10 with Juvapen and 2.24/10 with the standard technique (p = 0.0058; Z = 2.75). In patients with contracture-related pain, the average NRS score was 3.53 before BT injection, and 0.41 one month after BT injection (p = 0.0001). CONCLUSIONS: Juvapen is a less-painful injection technique than the standard one. BT reduces contracture-related pain one month after injection.

COVID-19-related anosmia is associated with viral persistence and inflammation in human olfactory epithelium and brain infection in hamsters.

Whereas recent investigations have revealed viral, inflammatory, and vascular factors involved in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lung pathogenesis, the pathophysiology of neurological disorders in coronavirus disease 2019 (COVID-19) remains poorly understood. Olfactory and taste dysfunction are common in COVID-19, especially in mildly symptomatic patients. Here, we conducted a virologic, molecular, and cellular study of the olfactory neuroepithelium of seven patients with COVID-19 presenting with acute loss of smell. We report evidence that the olfactory neuroepithelium is a major site of SARS-CoV2 infection with multiple cell types, including olfactory sensory neurons, support cells, and immune cells, becoming infected. SARS-CoV-2 replication in the olfactory neuroepithelium was associated with local inflammation. Furthermore, we showed that SARS-CoV-2 induced acute anosmia and ageusia in golden Syrian hamsters, lasting as long as the virus remained in the olfactory epithelium and the olfactory bulb. Last, olfactory mucosa sampling from patients showing long-term persistence of COVID-19-associated anosmia revealed the presence of virus transcripts and of SARS-CoV-2-infected cells, together with protracted inflammation. SARS-CoV-2 persistence and associated inflammation in the olfactory neuroepithelium may account for prolonged or relapsing symptoms of COVID-19, such as loss of smell, which should be considered for optimal medical management of this disease.

Positive predictive value for diffusion-weighted magnetic resonance imaging in pediatric cholesteatoma: A retrospective study.

OBJECTIVES: The aims of this study were first to calculate the Positive Predictive Value (PPV) of DW-MRI to detect cholesteatoma and then to analyze false positives. METHODS: All temporal bone MRI with DWI sequences performed in our pediatric university hospital between 2005 and 2015 were included retrospectively. 46 patients with a cholesteatoma diagnosis on the MRI report and who underwent surgery were studied. RESULTS: The number of DW-MRI for identification of cholesteatoma has grown in ten years. We calculated an 89% Positive Predictive Value. DW-MRI sensitivities were 100.0% and 70.7% for respectively keratin and squamous epithelium. CONCLUSION: DW-MRI hypersignal is not synonymous of cholesteatoma diagnosis. Indeed, this diagnosis relies on the importance of a proper otoscopic examination, a suggestive medical history, CT scan data and analysis of other MRI sequences, including T1-weighted sequence, to rule out other etiologies of middle ear DW-MRI hypersignal.

Nivolumab increases pulmonary artery pressure in patients treated for non-small cell lung cancer.

PURPOSE: The widespread use of Nivolumab results in an increasing number of side effects and adverse events. Herein, we evaluated the impact of Nivolumab on crude and normalized pulmonary artery diameter (PAD). METHODS: We analyzed clinical, morphometric, pathological and radiological data of lung cancer patients treated by Nivolumab in an 18-month period. Blinded radiological evaluation was performed, by three observers measuring axial PAD and Aorta diameter (AoD) in secondarily matched pre- and post-Nivolumab CT-scans. Correlation between ΔPAD and clinicopathological data was investigated. RESULTS: 59 patients receiving Nivolumab for treatment of advanced lung carcinoma were identified. Pre-and post-Nivolumab comparison of CT-scan measures revealed that mean PAD was 26.3 ± 2.8 mm versus 28.0 ± 3.0 mm (p < 0.001), and mean PAD/AoD ratio was 0.82 ± 0.09 versus 0.87 ± 0.11 (p < 0.001), respectively. Median ΔPAD was 0.05 [0.01-0.122] was significantly higher in hypometabolic patients exhibiting low Rest Energy Expenditure (p = 0.03). Patients exhibiting ΔPAD > 1% had significantly lower serum albumin level (p = 0.03), and higher nutritional risk (p = 0.02), compared to others. Unlike Nivolumab therapy, there was no increase of PAD after chemotherapy in the same cohort of patients with available scans (n = 45, 25.9 ± 2.9 mm pre-chemotherapy versus 25.7 ± 2.4 mm post-chemotherapy, p = 0.51). Anti-PD-1 treatment was associated with immune-related adverse events in 11 (18.6%) cases including 2 cases of life-threatening acute pulmonary hypertension, both exhibiting post-treatment PAD/AoD ratio > 1. CONCLUSION: Nivolumab is associated to PAD enlargement, a potential marker of pulmonary hypertension, sometimes leading to lethal adverse events. Careful CT-scan and echocardiographic evaluation of PAD should be part of the therapeutic work-up of patients receiving Nivolumab, especially those suffering cancer-associated malnutrition.

Transoral vertebroplasty for the C1 lateral mass.

BACKGROUND: Osteolytic lesions of the atlas (C1) are challenging to treat by vertebroplasty due to the vicinity of the vertebral artery and the spinal cord. OBJECTIVE: To present our experience with transoral vertebroplasty (TOV) for osteolytic lesions of the lateral mass of the atlas. METHODS: Retrospective case series involving 15 consecutive patients (nine male, six female, mean age 63 years) who underwent TOV for the treatment of an osteolytic lesion of the lateral mass of the atlas. Among the osteolytic lesions, 10/15 (67%) were bone metastases from various cancers; 4/15 (27%) were lesions related to multiple myeloma; and one lesion (7%) was an aggressive hemangioma. All the TOVs were performed under general anesthesia and in most cases (10/15; 67%) in a hybrid angiosuite combining a C-arm flat panel and a CT scan. The remaining five patients were treated under biplane fluoroscopic guidance. RESULTS: Vertebroplasty of the lateral mass of C1 through a transoral route was feasible in all cases. Significant pain relief was obtained in most cases (1 month average decrease in Numeric Rating Scale: 4.9±4.1). No major complication was recorded. In 7/15 cases (47%), cement leakage surrounding the C1 lateral mass was seen; none of these leakages had a significant clinical consequence. No additional spine surgery was required in any of the patients. CONCLUSION: TOV of osteolytic lesions of the lateral mass of the atlas is feasible and seems safe and effective, providing pain relief and bone stabilization.

Computed Tomography Description of the Uncinate Process Angulation in Patients With Cystic Fibrosis and Comparison With Primary Ciliary Dyskinesia, Nasal Polyposis, and Controls.

BACKGROUND:: There is a medial bulging of the lateral nasal wall in patients with cystic fibrosis (CF). AIMS:: Uncinate process (UP) angulation measurements in patients and controls to objectify this bulging. MATERIALS AND METHODS:: Thirty CF, 17 primary ciliary dyskinesia (PCD), 13 chronic rhinosinusitis with polyps (CRSwp), and 30 controls were included. Angles were measured bilaterally on computed tomography (CT) scans: A, B, C on coronal sections, D and E on axial sections. Angle A was between the UP and the orbit inner wall, whereas the others were between UP and midline. RESULTS:: There was no significant difference between controls, PCD, and CRSwp. However, CF had 3 statistically different angles with controls, 5 with CRSwp, and 4 with PCD. Angle A average value was 126° (±16°) in patients with CF, 138° (±19°) in controls ( P = .007), 145° (±15°) in PCD ( P = .001), and 138° (±14°) in CRSwp ( P = .001). Angle E average value was 35° (±10°) in patients with CF, 20° (±6°) in controls ( P < .001), 21° (±4°) in PCD ( P < .001), and 22° (±6°) in CRSwp ( P < .001). CONCLUSION:: Uncinate process's anatomy is only modified in CF: Angle between UP and inner wall of orbit is closed, and angles between UP and midline are opened. SIGNIFICANCE:: These measures quantify the medial bulging of lateral nasal wall and support nasofibroscopic observations.

Imaging Criteria to Predict Surgical Difficulties During Stapes Surgery.

BACKGROUND AND PURPOSE: Stapes surgery for otosclerosis can be challenging if access to the oval window niche is restricted. The aim of this study was to determine the accuracy of the computed tomographic (CT) scan in the evaluation of anatomical distances, and to analyze its reliability in predicting surgical technical difficulties. MATERIAL AND METHODS: A total of 96 patients (101 ears) were enrolled in a prospective study between 2012 and May 2015. During surgery, we evaluated the distance D1 between the stapes and the facial nerve, distance D2 between the promontory and the facial nerve after ablation of the superstructure, and the intraoperative discomfort of the surgeon. On preoperative CT scans, we measured the width and depth of the oval window niche, and the angle formed by two axes starting from the center-point of the footplate, the first tangential to the superior wall of the promontory, and the second tangential to the inferior wall of the fallopian canal. RESULTS: Intraoperative distances D1 and D2 were correlated with the width of the oval window and with the facial-promontory angle measured on imaging. CT scan measurements of the facial-promontory angle and width of the oval window were associated with the degree of discomfort of the surgeon. The cut-off threshold for intraoperative subjective discomfort was computed as 1.1 mm for the width of the oval window niche, with a sensibility of 71% and a specificity of 84%. CONCLUSION: Preoperative imaging analysis of the oval window width and the facialpromontory angle can predict operative difficulty in otosclerosis surgery.