Long-term treatment outcomes in refractory rhinitis medicamentosa managed with nasal surgery.

BACKGROUND: Limited treatment options exist for refractory Rhinitis Medicamentosa (RM). The role of surgery after failed medical management is not well defined. Mucosal contact points and restricted airflow often perpetuate decongestant use. This study assessed the long-term outcomes of nasal surgery in patients with refractory RM. METHODS: A prospective cohort study of refractory RM treated with nasal surgery was performed with ≥12 months follow-up. Refractory RM was defined as nasal decongestant use once per day continuously for ≥4 weeks despite medical therapy. Patients with concomitant sinus disease and nonrhinitis conditions were excluded. Sinonasal Outcome Test (SNOT22), Nasal Symptom Score (NSS), and nasal medication use were assessed. Patients who ceased decongestants were compared with ongoing users. RESULTS: A total of 56 patients (age 48.4 [5.0] years, 50% female) were assessed. Median follow-up was 3.4(1.6-6.2) years. Total cessation of decongestants was achieved in 91.1%, while 5.4% had intermittent use, and 3.6% reported daily use. Ongoing users had higher odds of concomitant asthma (40.0% vs. 3.9%; odds ratio [OR], 16.33 [1.7-159.75]; p = 0.036), reduced symptom improvement (ΔSNOT22, -4.6 [15.7] vs. 27.1 [17], p = 0.009 and ΔNSS, -1.0 [4.2] vs. -6.6 [5.1], p = 0.025), and greater ongoing use of nasal corticosteroid (60.0% vs. 5.9%; OR 24.0 [2.8-203.1]) and saline sprays (40% vs. 3.9%; OR 16.3 [1.7-159.8]) but showed no difference in allergy status (OR, 0.7[0.1-7.1]), previous surgery (OR, 1.0[0.1-10.2]), gastroesophageal reflux (OR 1.0[0.1-10.2], or underlying anxiety/depression (OR 6.1[0.8-45.9]) compared with those who ceased. CONCLUSION: Surgically re-establishing a nasal airway was associated with long-term decongestant cessation and symptom improvement in medically refractory RM.

3D-reconstructions of Bast's Valve and Membranous Labyrinth: Insights for Vestibular Implantation and Meniere's Disease.

HYPOTHESIS/BACKGROUND: Bast's valve is a poorly understood inner ear structure located at the junction between pars superior and inferior in the membranous labyrinth. Anatomically precise three-dimensional reconstructions (3D-reconstructions) of Bast's valve can help illuminate the morphology of the valve, and point toward its role in normal physiology and pathological states such as endolymphatic hydrops. This is of particular relevance to the development of a vestibular implant, a device intended to rehabilitate deficits in the vestibular system. METHODS: Six postmortem human temporal bones from healthy donors were scanned using a micro-computed tomography (microCT) scanner. The microCT data allowed 3D-reconstructions of the membranous labyrinth, with a particular focus on Bast's valve, vestibule, and cochlear duct. RESULTS: The microCT images of Bast's valve showed a rigid lip containing a core of soft tissue, opposing the thin membranous wall of the utricle. The maximum recorded length and width of the rigid lip were 440.4 µm and 88 µm, respectively. The 3D-reconstructions illustrated the slit-like opening of Bast's valve into the utricle, the twisting course of the basal turn of the cochlear duct, and the spatial orientation of utricle and saccule with respect to the stapes footplate. CONCLUSIONS: The present study provided a novel anatomical perspective on the microscopic structure of Bast's valve. The interplay between endolymphatic hydrops and Bast's valve is an ongoing area of research, but defining this anatomy in 3D will play a key role in furthering our understanding of the disease process. Implications for vestibular implantation are explored through the various 3D-reconstructions.

Yield of comparative genomic hybridization microarray in pediatric neurology practice.

OBJECTIVE: The present study investigated the diagnostic yield of array comparative genomic hybridization (aCGH) in a large cohort of children with diverse neurologic disorders as seen in child neurology practice to test whether pathogenic copy number variants (CNVs) were more likely to be detected in specific neurologic phenotypes. METHODS: A retrospective cross-sectional analysis was performed on 555 children in whom a genetic etiology was suspected and who underwent whole-genome aCGH testing between 2006 and 2012. Neurologic phenotyping was performed using hospital medical records. An assessment of pathogenicity was made for each CNV, based on recent developments in the literature. RESULTS: Forty-seven patients were found to carry a pathogenic CNV, giving an overall diagnostic yield of 8.59%. Certain phenotypes predicted for the presence of a pathogenic CNV, including developmental delay (odds ratio [OR] 3.69 [1.30-10.51]), cortical visual impairment (OR 2.73 [1.18-6.28]), dysmorphism (OR 2.75 [1.38-5.50]), and microcephaly (OR 2.16 [1.01-4.61]). The combination of developmental delay/intellectual disability with dysmorphism and abnormal head circumference was also predictive for a pathogenic CNV (OR 2.86 [1.02-8.00]). For every additional clinical feature, there was an increased likelihood of detecting a pathogenic CNV (OR 1.18 [1.01-1.38]). CONCLUSIONS: The use of aCGH led to a pathogenic finding in 8.59% of patients. The results support the use of aCGH as a first tier investigation in children with diverse neurologic disorders, although whole-genome sequencing may replace aCGH as the detection method in the future. In particular, the yield was increased in children with developmental delay, dysmorphism, cortical visual impairment, and microcephaly.

Mutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia.

Histone lysine methylation, mediated by mixed-lineage leukemia (MLL) proteins, is now known to be critical in the regulation of gene expression, genomic stability, cell cycle and nuclear architecture. Despite MLL proteins being postulated as essential for normal development, little is known about the specific functions of the different MLL lysine methyltransferases. Here we report heterozygous variants in the gene KMT2B (also known as MLL4) in 27 unrelated individuals with a complex progressive childhood-onset dystonia, often associated with a typical facial appearance and characteristic brain magnetic resonance imaging findings. Over time, the majority of affected individuals developed prominent cervical, cranial and laryngeal dystonia. Marked clinical benefit, including the restoration of independent ambulation in some cases, was observed following deep brain stimulation (DBS). These findings highlight a clinically recognizable and potentially treatable form of genetic dystonia, demonstrating the crucial role of KMT2B in the physiological control of voluntary movement.