Vigabatrin and Visual Field Defects in Pediatric Epilepsy Patients

We studied the prevalence, type and severity of vigabatrin (VGB)-attributed visual field defects (VFDs), and used these data to assess the associated risk factors in pediatric patients. Medical records were retrospectively reviewed for 67 pediatric patients who received VGB alone or in combination with other antiepileptic drugs, and who had undergone visual field examinations using a Humphrey visual field analyzer. Of the 67 patients, 15 had VGB-attributed VFDs: 13 had nasal arcuate type, 1 had nasal and temporal constricted type and 1 had nasal constricted type. In terms of severity, 7 patients had Grade I VGB-attributed VFDs, 5 had Grade II, 2 had Grade III, and 1 had Grade IV. Although there were no significant differences between the VFD and non-VFD groups with regards to all tested parameters, there were no cases of VGB-attributed VFDs in patients with total treatment durations <2 yr and cumulative doses <10 g/kg. In conclusion, the prevalence of VGB-attributed VFDs in VGB-treated pediatric epilepsy patients was 22%. The high frequency of VGB-attributed VFDs indicates that physicians should inform all patients of this risk prior to VGB treatment and perform periodic visual field examinations

Autoimmune Inner Ear Disease: Immune Biomarkers, Audiovestibular Aspects, and Therapeutic Modalities of Cogan’s Syndrome

Cogan’s syndrome (CS) is a rare autoimmune disorder characterized by audiovestibular dysfunction and ocular inflammation. Currently, there is no specific serum autoantibody used in the diagnostic workup of CS. Treatment is based on immunosuppressive agents, mainly corticosteroids as first-line choice. Recently, novel therapeutic modalities in CS have emerged. These include tumor necrosis factor-α inhibitors and other biologicals. Despite medical treatment, hearing loss may progress to irreversible bilateral profound SNHL in approximately half of CS patients resulting in candidacy for cochlear implantation (CI). Due to the inflammatory nature of the disease that is causing endosteal reaction with partial obliteration or complete neoossification of the intracochlear ducts, early CI is recommended. CI provides excellent and stable hearing rehabilitation with high score of word and sentence recognition. In this review, we will discuss different aspects of CS including clinical presentation, diagnosis, treatment, and future directives

Sinonasal Stent Coated with Slow-Release Varnish of Chlorhexidine Has Sustained Protection against Bacterial Biofilm Growth in the Sinonasal Cavity: An In Vitro Study

The aim of the study was to develop a sustained-release varnish (SRV) containing chlorhexidine (CHX) for sinonasal stents (SNS) to reduce bacterial growth and biofilm formation in the sinonasal cavity. Segments of SNS were coated with SRV-CHX or SRV-placebo and exposed daily to bacterial cultures of Staphylococcus aureus subsp. aureus ATCC 25923 or Pseudomonas aeruginosa ATCC HER-1018 (PAO1). Anti-bacterial effects were assessed by disc diffusion assay and planktonic-based activity assay. Biofilm formation on the coated stents was visualized by confocal laser scanning microscopy (CLSM) and high-resolution scanning electron microscopy (HR-SEM). The metabolic activity of the biofilms was determined using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) method. Disc diffusion assay showed that SRV-CHX-coated SNS segments inhibited bacterial growth of S. aureussubsp. aureus ATCC 25923 for 26 days and P. aeruginosa ATCC HER-1018 for 19 days. CHX was released from coated SNS segments in a pH 6 medium up to 30 days, resulting in growth inhibition of S. aureussubsp. aureus ATCC 25923 for 22 days and P. aeruginosa ATCC HER-1018 for 24 days. The MTT assay showed a reduction of biofilm growth on the coated SNS by 69% for S. aureussubsp. aureus ATCC 25923 and 40% for P. aeruginosa ATCC HER-1018 compared to the placebo stent after repeated exposure to planktonic growing bacteria. CLSM and HR-SEM showed a significant reduction of biofilm formation on the SRV-CHX-coated SNS segments. Coating of SNS with SRV-CHX maintains a sustained delivery of CHX, providing an inhibitory effect on the bacterial growth of S. aureussubsp. aureus ATCC 25923 and P. aeruginosa ATCC HER-1018 for approximately 3 weeks

Exome Sequencing Identifies a Founder Frameshift Mutation in an Alternative Exon of <em>USH1C</em> as the Cause of Autosomal Recessive Retinitis Pigmentosa with Late-Onset Hearing Loss

<div><p>We used a combined approach of homozygosity mapping and whole exome sequencing (WES) to search for the genetic cause of autosomal recessive retinitis pigmentosa (arRP) in families of Yemenite Jewish origin. Homozygosity mapping of two arRP Yemenite Jewish families revealed a few homozygous regions. A subsequent WES analysis of the two index cases revealed a shared homozygous novel nucleotide deletion (c.1220delG) leading to a frameshift (p.Gly407Glufs*56) in an alternative exon (#15) of <em>USH1C</em>. Screening of additional Yemenite Jewish patients revealed a total of 16 homozygous RP patients (with a carrier frequency of 0.008 in controls). Funduscopic and electroretinography findings were within the spectrum of typical RP. While other <em>USH1C</em> mutations usually cause Usher type I (including RP, vestibular dysfunction and congenital deafness), audiometric screening of 10 patients who are homozygous for c.1220delG revealed that patients under 40 years of age had normal hearing while older patients showed mild to severe high tone sensorineural hearing loss. This is the first report of a mutation in a known USH1 gene that causes late onset rather than congenital sensorineural hearing loss. The c.1220delG mutation of <em>USH1C</em> accounts for 23% of RP among Yemenite Jewish patients in our cohort.</p> </div

Audiometric results of patients who are homozygous for the <i>USH1C</i> c.1220delG mutation.

<p>A. Patient MOL0486 II:3 (13 yo) with normal hearing function. B. Patient MOL0887-3 (44 yo) with severe SNHL, particularly at higher frequencies (descending pattern). C,D. Hearing threshold versus age at a frequency of 4,000 Hz (C) and 8,000 Hz (D). At younger ages, normal hearing function is evident, but after the age of 40 years, sensitivity is markedly reduced. For each of the 10 patients, the data from both the right and left ears is presented, showing symmetry between both ears.</p