Assessment of Intraoperative Nerve Monitoring Parameters Associated With Facial Nerve Outcome in Parotidectomy for Benign Disease.

Importance: Prior studies suggest that the use of facial nerve monitoring decreases the rate of immediate postoperative facial nerve weakness in parotid surgery, but published data are lacking on normative values for these parameters or cutoff values to prognosticate facial nerve outcomes. Objective: To identify intraoperative facial nerve monitoring parameters associated with postoperative weakness and to evaluate cutoff values for these parameters under which normal nerve function is more likely. Design, Setting, and Participants: This retrospective case series of 222 adult patients undergoing parotid surgery for benign disease performed with intraoperative nerve monitoring was conducted at an academic medical institution from September 13, 2004, to October 30, 2014. The data analysis was conducted from May 2018 to January 2019. Main Outcomes and Measures: The main outcome measure was facial nerve weakness. Receiver operating characteristic curves were generated to define optimal cut point to maximize the sensitivity and specificity of the stimulation threshold, mechanical events, and spasm events associated with facial nerve weakness. Results: Of 222 participants, 121 were women and 101 were men, with a mean (SD) age of 51 (16) years. The rate of temporary facial nerve paresis of any nerve branch was 45%, and the rate of permanent paralysis was 1.3%. The mean predissection threshold was 0.22 milliamperes (mA) (range, 0.1-0.6 mA) and the mean postdissection threshold was 0.24 mA (range, 0.08-1.0 mA). The average number of mechanical events was 9 (range, 0-66), and mean number of spontaneous spasm events was 1 (range, 0-12). Both the postdissection threshold (area under the curve [AUC], 0.69; 95% CI, 0.62-0.77) and the number of mechanical events (AUC, 0.58; 95% CI, 0.50-0.66) were associated with early postoperative facial nerve outcome. The number of spasm events was not associated with facial nerve outcome. The optimal cutoff value for the threshold was 0.25 mA, and the optimal cutoff for number of mechanical events was 8. If a threshold of greater than 0.25 mA was paired with more than 8 mechanical events, there was a 77% chance of postoperative nerve weakness. Conversely, if a threshold was 0.25 mA or less and there were 8 mechanical events or less, there was 69% chance of normal postoperative nerve function. No parameters were associated with permanent facial nerve injury. Conclusions and Relevance: Postdissection threshold and the number of mechanical events are associated with immediate postoperative facial nerve function. Accurate prediction of facial nerve function may provide anticipatory guidance to patients and may provide surgeons with intraoperative feedback allowing adjustment in operative techniques and perioperative management.

Electrocochleography Results in Patients With Bilateral Vestibular Paresis and Sound- or Pressure-Induced Horizontal Nystagmus.

OBJECTIVE: To describe the electrocochleography (ECochG) findings in patients with bilateral vestibular paresis and sound- and/or pressure-induced horizontal nystagmus. DESIGN: Retrospective case series. SETTING: Tertiary care center. PATIENTS: Three adult patients with bilateral vestibular paresis and sound- and/or pressure-induced horizontal nystagmus were evaluated from 2012 to 2016. MAIN OUTCOME MEASURE: All patients underwent ECochG, vestibular evoked myogenic potential (VEMP) testing, bithermal caloric testing, rotary chair testing, audiometric testing, and temporal bone computed tomography (CT). For ECochG, the summating potential (SP) to action potential (AP) ratio was determined. RESULTS: All patients had normal temporal bone CT, reduced caloric responses bilaterally, decreased gain on rotary chair, and abnormal ECochG. For two subjects, the SP/AP was elevated bilaterally. One subject had unilateral SP/AP elevation. Cervical VEMPs were present in all subjects, but at reduced thresholds in two subjects. CONCLUSION: SP/AP elevation was found in all three patients with the syndrome of bilateral vestibular paresis and/or sound- or pressure-induced horizontal nystagmus. As the etiology of this syndrome remains unclear, understanding the basis for abnormal ECochG may shed insight into the pathophysiology of this condition.

Prevalence of hearing and vestibular loss in cystic fibrosis patients exposed to aminoglycosides.

AIM: Cystic Fibrosis (CF) patients frequently use aminoglycosides (AGS) to treat CF exacerbation due to colonization with Pseudomonas aeruginosa. Although AGS can cause vestibular and auditory sensory losses that can negatively impact quality of life, little is known about the prevalence of vestibular loss in this population. The aim of this study was to determine the prevalence of hearing loss and/or vestibular dysfunction in CF patients treated with AGS. METHODS: The relationship between hearing status and vestibular status was also investigated. Hearing was determined to be normal or abnormal based on pure tone air and bone conduction thresholds. Vestibular outcome was divided into four categories; normal, non-lateralized vestibular dysfunction, unilateral loss, and bilateral loss based on results of post head shaking testing, positional and positioning testing, bithermal calorics, sinusoidal, and rotational step testing. RESULTS: Of our cohort of 71 patients, 56 (79%) patients have vestibular system dysfunction while only 15 (21%) have normal vestibular system function. Overall, 16 patients (23%) have hearing loss. In considering the relationship between auditory and vestibular function, 12 (17%) demonstrated both normal hearing and normal vestibular function and 13 (18%) have both hearing loss and abnormal vestibular function. Of the 55 (78%) patients with normal hearing, 43 (61%) have vestibular dysfunction, while 3 (4%) of patients with normal vestibular function have hearing loss. CONCLUSION: These results suggest that monitoring hearing alone is insufficient to detect ototoxicity in CF patients being treated with systemic AGS.

Site specific N6-(2-hydroxy-3,4-epoxybut-1-yl)adenine oligodeoxynucleotide adducts of 1,2,3,4-diepoxybutane: synthesis and stability at physiological pH.

1,2,3,4-Diepoxybutane (DEB) is an important metabolite of 1,3-butadiene, a high volume industrial chemical classified as a human and animal carcinogen. DEB is a bifunctional alkylating agent that exhibits both mutagenic and cytotoxic activity, presumably a result of its ability to form bifunctional DNA adducts. Initial reactions of DEB with DNA produce 2-hydroxy-3,4-epoxybut-1-yl (HEB) lesions at guanine and adenine nucleobases. The epoxy group of the monoadduct is inherently reactive and can then undergo further reactions, for example, hydrolysis to the corresponding 2,3,4-trihydroxybutyl adducts and/or second alkylation to yield 2,3-butanediol cross-links. In the present work, synthetic DNA 16-mers containing structurally defined racemic N6-(2-hydroxy-3,4-epoxybut-1-yl)-2'-deoxyadenosine (N6-HEB-dA) adducts (5'-AATTATGTXACGGTAG-3', where X = N6-HEB-dA) were prepared by coupling 6-chloropurine-containing oligodeoxynucleotides with 1-amino-2-hydroxy-3,4-epoxybutane. The latter was generated in situ from the corresponding Fmoc-protected amino epoxide. The N6-HEB-dA-containing DNA oligomer was isolated by reverse-phase HPLC, and the presence of N6-HEB-dA in its structure was confirmed by molecular weight determination and by HPLC-UV-ESI+-MS/MS analyses of enzymatic digests. An independently prepared N6-HEB-dA nucleoside served as an authentic standard. The fate of N6-HEB-dA within DNA at physiological conditions in the presence of various nucleophiles (e.g., cysteine, dG, and the complementary DNA strand) was investigated. Under all conditions tested, N6-HEB-dA rapidly cyclized to produce previously unidentified exocyclic dA lesions (t1/2 < 2 h at physiological conditions). Only trace amounts of hydrolyzed and cross-linked products were detected, suggesting that the rate of cyclization was much greater than the rates of other reactions at the epoxide ring. These results indicate that DEB-induced alkylation of N6-adenine in DNA is unlikely to lead to DNA-DNA cross-linking but instead can result in the formation of exocyclic dA adducts.