Lack of neural contributions to the summating potential in humans with Meniere's disease.

Objective: To investigate the electrophysiology of the cochlear summating potential (SP) in patients with Meniere's disease (MD). Although long considered a purely hair cell potential, recent studies show a neural contribution to the SP. Patients with MD have an enhanced SP compared to those without the disease. Consequently, this study was to determine if the enhancement of the SP was in whole or part due to neural dysfunction. Design: Study participants included 41 adults with MD and 53 subjects with auditory neuropathy spectrum disorder (ANSD), undergoing surgery where the round window was accessible. ANSD is a condition with known neural dysfunction, and thus represents a control group for the study. The ANSD subjects and 17 of the MD subjects were undergoing cochlear implantation (CI) surgery; the remaining MD subjects were undergoing either endolymphatic sac decompression or labyrinthectomy to alleviate the symptoms of MD. Electrocochleography was recorded from the round window using high intensity (90 dB nHL) tone bursts. The SP and compound action potential (CAP) were measured to high frequencies (> = 2 kHz) and the SP, cochlear microphonic (CM) and auditory nerve neurophonic (ANN) to low frequencies. Linear mixed models were used to assess differences between MD and ANSD subjects. Results: Across frequencies, the MD subjects had smaller alternating current (AC) response than the ANSD subjects (F = 31.61,534, p < 0.001), but the SP magnitudes were larger (F = 94.31,534, p < 0.001). For frequencies less than 4 kHz the SP magnitude in the MD group was significantly correlated with the magnitude of the CM (p's < 0.001) but not in the ANSD group (p's > 0.05). Finally, the relative proportions of both ANN and CAP were greater in MD compared to ANSD subjects. The shapes of the waveforms in the MD subjects showed the presence of multiple components contributing to the SP, including outer and inner hair cells and neural activity. Conclusion: The results support the view that the increased negative polarity SP in MD subjects is due to a change in the operating point of hair cells rather than a loss of neural contribution. The steady-state SP to tones in human subjects is a mixture of different sources with different polarities.

Round Window Electrocochleography to Low Frequency Tones in Pediatric Cochlear Implant Recipients with and Without Auditory Neuropathy Spectrum Disorder: Separating Hair Cell and Neural Contributions Using a Computational Model.

HYPOTHESIS: Characterize the contribution of the auditory nerve neurophonic (ANN) to electrocochleography (ECochG) of pediatric cochlear implant (CI) recipients with and without auditory nerve spectrum disorder (ANSD). BACKGROUND: ECochG is an emerging technique for predicting outcomes in CI recipients. Its utility may be increased by separating the cochlear microphonic (CM), produced by hair cells, from the ANN, the evoked potential correlate of neural phase-locking, which are mixed in the ongoing portion of the response to low frequency tone bursts. METHODS: Responses to tone bursts of different frequency and intensities were recorded from the round window of pediatric CI recipients. Separation of the CM and ANN was performed using a model of the underlying processes that lead to the shapes of the observed waveforms. RESULTS: Preoperative mean pure tone amplitudes of the included ANSD (n = 36) and non-ANSD subjects (n = 123), were similar (89.5 and 93.5, p = 0.1). Total of 1,024 ECochG responses to frequency and intensity series were recorded. The mean correlation ( r ) between the input and the modeled signals was 0.973 ± 0.056 (standard deviation). The ANN magnitudes were higher in the ANSD group (ANOVAs, F = 26.5 for frequency and 21.9 for intensity, df's = 1, p 's < 0.001). However, its relative contribution to the overall signal was lower (ANOVAs, F = 25.8 and 12.1, df = 1, p 's < 0.001). CONCLUSIONS: ANN was detected in low frequency ECochG responses but not high frequency responses in both ANSD and non-ANSD subjects. ANSD subjects, evidence of neural contribution in responses to low frequency stimuli was highly variable and often comparable to signals recorded in non-ANSD subjects. The computational model revealed that on average the ANN comprised a lower proportion of the overall signal than in non-ANSD subjects.

Residual Cochlear Function in Adults and Children Receiving Cochlear Implants: Correlations With Speech Perception Outcomes.

OBJECTIVES: Variability in speech perception outcomes with cochlear implants remains largely unexplained. Recently, electrocochleography, or measurements of cochlear potentials in response to sound, has been used to assess residual cochlear function at the time of implantation. Our objective was to characterize the potentials recorded preimplantation in subjects of all ages, and evaluate the relationship between the responses, including a subjective estimate of neural activity, and speech perception outcomes. DESIGN: Electrocochleography was recorded in a prospective cohort of 284 candidates for cochlear implant at University of North Carolina (10 months to 88 years of ages). Measurement of residual cochlear function called the "total response" (TR), which is the sum of magnitudes of spectral components in response to tones of different stimulus frequencies, was obtained for each subject. The TR was then related to results on age-appropriate monosyllabic word score tests presented in quiet. In addition to the TR, the electrocochleography results were also assessed for neural activity in the forms of the compound action potential and auditory nerve neurophonic. RESULTS: The TR magnitude ranged from a barely detectable response of about 0.02 µV to more than 100 µV. In adults (18 to 79 years old), the TR accounted for 46% of variability in speech perception outcome by linear regression (r = 0.46; p < 0.001). In children between 6 and 17 years old, the variability accounted for was 36% (p < 0.001). In younger children, the TR accounted for less of the variability, 15% (p = 0.012). Subjects over 80 years old tended to perform worse for a given TR than younger adults at the 6-month testing interval. The subjectively assessed neural activity did not increase the information compared with the TR alone, which is primarily composed of the cochlear microphonic produced by hair cells. CONCLUSIONS: The status of the auditory periphery, particularly of hair cells rather than neural activity, accounts for a large fraction of variability in speech perception outcomes in adults and older children. In younger children, the relationship is weaker, and the elderly differ from other adults. This simple measurement can be applied with high throughput so that peripheral status can be assessed to help manage patient expectations, create individually-tailored treatment plans, and identify subjects performing below expectations based on residual cochlear function.

A Model-Based Approach for Separating the Cochlear Microphonic from the Auditory Nerve Neurophonic in the Ongoing Response Using Electrocochleography.

Electrocochleography (ECochG) is a potential clinically valuable technique for predicting speech perception outcomes in cochlear implant (CI) recipients, among other uses. Current analysis is limited by an inability to quantify hair cell and neural contributions which are mixed in the ongoing part of the response to low frequency tones. Here, we used a model based on source properties to account for recorded waveform shapes and to separate the combined signal into its components. The model for the cochlear microphonic (CM) was a sinusoid with parameters for independent saturation of the peaks and the troughs of the responses. The model for the auditory nerve neurophonic (ANN) was the convolution of a unit potential and population cycle histogram with a parameter for spread of excitation. Phases of the ANN and CM were additional parameters. The average cycle from the ongoing response was the input, and adaptive fitting identified CM and ANN parameters that best reproduced the waveform shape. Test datasets were responses recorded from the round windows of CI recipients, from the round window of gerbils before and after application of neurotoxins, and with simulated signals where each parameter could be manipulated in isolation. Waveforms recorded from 284 CI recipients had a variety of morphologies that the model fit with an average r2 of 0.97 ± 0.058 (standard deviation). With simulated signals, small systematic differences between outputs and inputs were seen with some variable combinations, but in general there were limited interactions among the parameters. In gerbils, the CM reported was relatively unaffected by the neurotoxins. In contrast, the ANN was strongly reduced and the reduction was limited to frequencies of 1,000 Hz and lower, consistent with the range of strong neural phase-locking. Across human CI subjects, the ANN contribution was variable, ranging from nearly none to larger than the CM. Development of this model could provide a means to isolate hair cell and neural activity that are mixed in the ongoing response to low-frequency tones. This tool can help characterize the residual physiology across CI subjects, and can be useful in other clinical settings where a description of the cochlear physiology is desirable.

Intraoperative Electrocochleographic Characteristics of Auditory Neuropathy Spectrum Disorder in Cochlear Implant Subjects.

Auditory neuropathy spectrum disorder (ANSD) is characterized by an apparent discrepancy between measures of cochlear and neural function based on auditory brainstem response (ABR) testing. Clinical indicators of ANSD are a present cochlear microphonic (CM) with small or absent wave V. Many identified ANSD patients have speech impairment severe enough that cochlear implantation (CI) is indicated. To better understand the cochleae identified with ANSD that lead to a CI, we performed intraoperative round window electrocochleography (ECochG) to tone bursts in children (n = 167) and adults (n = 163). Magnitudes of the responses to tones of different frequencies were summed to measure the "total response" (ECochG-TR), a metric often dominated by hair cell activity, and auditory nerve activity was estimated visually from the compound action potential (CAP) and auditory nerve neurophonic (ANN) as a ranked "Nerve Score". Subjects identified as ANSD (45 ears in children, 3 in adults) had higher values of ECochG-TR than adult and pediatric subjects also receiving CIs not identified as ANSD. However, nerve scores of the ANSD group were similar to the other cohorts, although dominated by the ANN to low frequencies more than in the non-ANSD groups. To high frequencies, the common morphology of ANSD cases was a large CM and summating potential, and small or absent CAP. Common morphologies in other groups were either only a CM, or a combination of CM and CAP. These results indicate that responses to high frequencies, derived primarily from hair cells, are the main source of the CM used to evaluate ANSD in the clinical setting. However, the clinical tests do not capture the wide range of neural activity seen to low frequency sounds.

Clinical role of electrocochleography in children with auditory neuropathy spectrum disorder.

OBJECTIVES: To assess electrocochleography (ECochG) to tones as an instrument to account for CI speech perception outcomes in children with auditory neuropathy spectrum disorder (ANSD). MATERIALS & METHODS: Children (<18 years) receiving CIs for ANSD (n = 30) and non-ANSD (n = 74) etiologies of hearing loss were evaluated with ECochG using tone bursts (0.25-4 kHz). The total response (TR) is the sum of spectral peaks of responses across frequencies. The compound action potential (CAP) and the auditory nerve neurophonic (ANN) in ECochG waveforms were used to estimate nerve activity and calculate nerve score. Performance on open-set monosyllabic word tests was the outcome measure. Standard statistical methods were applied. RESULTS: On average, TR was larger in ANSD than in non-ANSD subjects. Most ANSD (73.3%) and non-ANSD (87.8%) subjects achieved open-set speech perception; TR accounted for 33% and 20% of variability in the outcomes, respectively. In the ANSD group, the PTA accounted for 69.3% of the variability, but there was no relationship with outcomes in the non-ANSD group. In both populations, nerve score was sensitive in identifying subjects at risk for not acquiring open-set speech perception, while the CAP and the ANN were more specific. CONCLUSION: In both subject groups, the TRs correlated with outcomes but these measures were notably larger in the ANSD group. There was also strong correlation between PTA and speech perception outcome in ANSD group. In both subject populations, weaker evidence of neural activity was related to failure to achieve open-set speech perception.

The Compound Action Potential in Subjects Receiving a Cochlear Implant.

HYPOTHESIS: The compound action potential (CAP) is a purely neural component of the cochlea's response to sound, and may provide information regarding the existing neural substrate in cochlear implant (CI) subjects that can help account for variance in speech perception outcomes. BACKGROUND: Measurement of the "total response" (TR), or sum of the magnitudes of spectral components in the ongoing responses to tone bursts across frequencies, has been shown to account for 40 to 50% of variance in speech perception outcomes. The ongoing response is composed of both hair cell and neural components. This correlation may be improved with the addition of the CAP. METHODS: Intraoperative round window electrocochleography (ECochG) was performed in adult and pediatric CI subjects (n = 238). Stimuli were tones of different frequencies (250 Hz-4 kHz) at 90 dB nHL. The CAP was assessed in two ways, as an amplitude and with a scaling factor derived from a function fitted to the response. The results were correlated with consonant-nucleus-consonant (CNC) word scores at 6 months post-implantation (n = 51). RESULTS: Only about half of the subjects had a measurable CAP at any frequency. The CNC word scores correlated weakly with both amplitude (r = 0.20, p < 0.001) and scaling factor (r = 0.25, p < 0.01). In contrast, the TR alone accounted for 43% of the variance, and addition of either CAP measurement in multiple regression did not account for additional variance. CONCLUSIONS: The underlying pathology in CI patients causes the CAP to be often absent and highly variable when present. The TR is a better predictor of speech perception outcomes than the CAP.

Role of computed tomography angiography in the management of Zone II penetrating neck trauma in patients with clinical hard signs.

BACKGROUND: The Western Trauma Association (WTA) describes the management of Zone 2 penetrating neck trauma (PNT) and recommends neck exploration (NE) for patients with clinical hard signs (HS). We hypothesize that in stable patients with HS, the management of PNT augmented by computed tomography angiography (CTA) results in fewer negative NE results. METHODS: This was a 4-year retrospective review of adult patients with Zone 2 PNT at a Level I trauma center. Stable patients with WTA-defined HS (airway compromise, massive subcutaneous emphysema/air bubbling through wound, expanding/pulsatile hematoma, active bleeding, shock, focal neurologic deficit, and hematemesis) who underwent CTA instead of emergent exploration were identified. Sensitivity, specificity, positive predictive value, and negative predictive value for CTA were calculated. A comparison was made between the rates of negative NE results in patients with HS who received a CTA versus the rate that would have occurred in the same patients if the WTA algorithm had been followed. Missed injury rates were also compared. RESULTS: Of 183 PNT patients, 23 had HS and underwent CTA. Of the 23, 5 had a positive CTA findings and underwent NE, while 17 had a negative CTA findings and did not require NE. There was one false-negative in a patient who developed an expanding hematoma following negative neck CTA finding. Sensitivity, specificity, positive predictive value, and negative predictive value for CTA in the presence of HS were found to be 83%, 100%, 100%, and 94%, respectively. The addition of CTA to the WTA algorithm for this patient group significantly decreased the rate of negative NE (0 of 23 vs. 18 of 23, p < 0.001) without a significant increase in the rate of missed injury (1 of 23 vs. 0 of 23, p = 0.323). The use of CTA prevented 17 unnecessary NEs. CONCLUSION: CTA addition to the management of hemodynamically stable patients with HS in PNT significantly decreased the rate of negative NE result without increasing missed injury rate. Prospective study of CTA addition to the WTA algorithm is needed. LEVEL OF EVIDENCE: Care management/therapeutic study, level IV.

Percutaneous ethanol injection vs reoperation for locally recurrent papillary thyroid cancer: a systematic review and pooled analysis.

IMPORTANCE: Reoperation for recurrent papillary thyroid cancer (PTC) can be associated with a high rate of complications and failure to provide lasting remission. Percutaneous ethanol injection (PEI) may be an effective nonsurgical management option for locally recurrent PTC. OBJECTIVE: This systematic analysis of the current literature compares the efficacy and complications related to PEI vs reoperative surgical intervention for treatment of locally recurrent PTC. DATA SOURCES: Original studies were identified using the keywords "thyroid/ethanol" and "recurrent thyroid cancer/repeat surgery." STUDY SELECTION: Studies evaluating reoperation or PEI for lymph node metastases in patients with primary surgery of total thyroidectomy with appropriate lymph node dissection where indicated were included in the analysis for both reoperation and PEI. Animal studies, single case reports, and studies with fewer than 10 lesions were excluded. DATA EXTRACTION AND SYNTHESIS: Outcomes included interval to detection of recurrence, success and failure rates, recurrence rates, complication rates, and follow-up duration. Between-group outcome differences were calculated using random-effects models, and pooled data cross-tabulation and logistic regression analysis were used. RESULTS: In all, 945 publications were identified, and 27 studies met the inclusion criteria. There were no studies that directly compared the 2 treatment techniques. A total of 1617 patients were included in this analysis; 168 (11.4%) were treated with PEI, and 1449 (88.6%) were treated with reoperation. Reoperation was successful in 94.8% of cases compared with an 87.5% success rate for PEI (odds ratio [OR], 2.58; 95% CI, 1.55-4.31; P < .001). The recurrence rates for PEI and reoperation at the site of the treated lesion or elsewhere in the neck were also similar (OR, 1.07; 95% CI, 0.65-1.77; P = .78). Reoperation was associated with a 3.5% pooled risk of complications, while PEI incurred a pooled risk of 1.2% (OR, 2.9; 95% CI, 0.72-12.3; P = .08). However, most studies did not report routine preoperative and postoperative laryngoscopies, an evaluation needed for accurate neural complication analysis associated with each procedure. CONCLUSIONS AND RELEVANCE: High-quality, well-designed studies are needed to evaluate the feasibility of incorporating PEI into the treatment protocol of PTC. Although presently inferior to reoperation, PEI has the potential to be a widely accepted and effective nonsurgical treatment option for limited recurrent PTC in poor surgical candidates or patients seeking to avoid multiple reoperations.

RADIOLOGY OF THE MONTH: Pulmonary Langerhans Cell Histiocytosis (PLCH).

PURPOSE: Obtaining a tissue sample diagnostic of pulmonary Langerhans cell histiocytosis (PLCH) by transbronchial biopsy is notoriously difficult. The condition's appearance on computed tomography is well described and singularly characteristic, perhaps adequate for definitive diagnosis. We propose an approach to diagnosis of these patients. METHODS: Radiology case report of PLCH in a middle-aged female smoker with two week history of nonproductive cough, low grade fevers, and fatigue. RESULTS: Computed tomography (CT) provided the diagnosis of PLCH. Transbronchial biopsies failed to provide a definitive diagnosis. CONCLUSIONS: Utility of transbronchial biopsy in diagnosis of PLCH is limited. Patients who present with signs, symptoms and high resolution computed tomography typical of PLCH do not require a correlation by tissue diagnosis. If cancer is suspected, a wedge biopsy should be performed for tissue diagnosis.

Does intraoperative nerve monitoring reliably aid in staging of total thyroidectomies?

OBJECTIVES/HYPOTHESIS: Demonstrate whether intraoperative nerve monitoring is an effective tool in staging bilateral thyroid and neck surgeries in cases of intraoperative injury to the recurrent laryngeal nerve on the side of initial dissection. We hypothesized that IONM provides reliable and appropriate feedback on the functional status of the RLN on side of initial dissection during total thyroidectomy and central neck surgery. STUDY DESIGN: Case series with planned data collection. METHODS: All patients receiving total thyroidectomies or central neck surgeries were reviewed. The outcomes of patients treated whose procedures were staged based on intraoperative nerve monitoring are described. RESULTS: Ten (4.9%) of 206 procedures were staged based on unfavorable signal change including six patients with thyroid cancers and four with compressive substernal goiters. The overall signal drop in the 10 patients with unfavorable signal change was 63%. Three patients had complete loss of signal. In the other seven patients, the signal dropped by a mean of 48%. In the eight patients with laryngoscopy-proven vocal fold paresis, the signal dropped by a mean of 68%. CONCLUSIONS: Intraoperative nerve monitoring results accurately indicated postoperative ipsilateral vocal cord dysfunction with high reliability. Intraoperative nerve monitoring is a reliable tool in staging thyroid surgery. LEVEL OF EVIDENCE: 4.

Impact of infusion rates of fresh frozen plasma and platelets during the first 180 minutes of resuscitation.

BACKGROUND: Whether high-ratio resuscitation (HRR) provides patients with survival advantage remains controversial. We hypothesized a direct correlation between HRR infusion rates in the first 180 minutes of resuscitation and survival. STUDY DESIGN: This was a retrospective analysis of massively transfused trauma patients surviving more than 30 minutes and undergoing surgery at a level 1 trauma center. Mean infusion rates (MIR) of packed red blood cells (PRBC), fresh frozen plasma (FFP), and platelets (Plt) were calculated for length of intervention (emergency department [ED] time + operating room [OR] time). Patients were categorized as HRR (FFP:PRBC > 0.7, and/or Plts: PRBC > 0.7) vs low-ratio resuscitation (LRR). Student's t-tests and chi-square tests were used to compare survivors with nonsurvivors. Cox proportional hazards regression models and Kaplan-Meier curves were generated to evaluate the association between MIR for FFP:PRBC and Plt:PRBC and 180-minute survival. RESULTS: There were 151 patients who met criteria: 121 (80.1%) patients survived 180 minutes (MIR:PRBC 71.9 mL/min, FFP 92.0 mL/min, Plt 3.5 mL/min) vs 30 (19.9%) who did not survive (MIR:PRBC 47.3 mL/min, FFP 33.7 mL/min, Plt 1.1 mL/min), p = 0.43, p < 0.0001 and p < 0.011, respectively. A Cox regression model evaluated PRBC rate, FFP rate, and Plt rate (mL/min) as mortality predictors within 180 minutes to assess if they significantly affected survival (hazard ratios 1.01 [p = 0.054], 0.97 [p < 0.0001], and 0.75 [p = 0.01], respectively). Another model used stepwise Cox regression including PRBC rate, FFP rate, and Plt rate (hazard ratios 1.00 [p = 0.85], 0.97 [p < 0.0001], and 0.88 [p = 0.24], respectively), as well as possible confounding variables. CONCLUSIONS: This is the first study to examine effects of MIRs on survival. Further studies on the effects of narrow time-interval analysis for blood product resuscitation are warranted.

Gender, race, and electrophysiologic characteristics of the branched recurrent laryngeal nerve.

OBJECTIVES/HYPOTHESIS: The extralaryngeal branching of recurrent laryngeal nerves (RLN) conveys an increased risk of nerve injury during thyroid surgery. We hypothesized that racial and gender variations in prevalence of branched RLN exist. STUDY DESIGN: A retrospective review of all patients who underwent thyroid surgery in a 4-year period in a single surgeon practice. METHODS: The RLN was routinely identified during thyroid surgery. Presence of RLN branching, its distance from the laryngeal nerve entry point (NEP), and functionality of the branches were ascertained. Patient demographics, rates of neural branching, and distance of bifurcation from the NEP were evaluated using statistical analysis. RESULTS: We identified 719 RLNs at risk in 491 patients who underwent central neck surgery. Four hundred and five (82.5%) patients were female and 86 (17.5%) patients were male. There were 218 (44.4%) African American patients and 251 (51.1 %) Caucasian patients. In African American patients, 42.1% RLNs bifurcated compared to 33.2% RLNs in Caucasian (P = 0.017) patients. The RLNs of African American and Caucasian patients bifurcated at comparable distances (P = 0.30). In male patients, 39.1% RLNs bifurcated; whereas in female patients 36.2% RLNs bifurcated (P = 0.53). On average, RLN bifurcation in female patients was at a longer distance from NEP compared to that of male patients (P = 0.012). Electrophysiologic testing found motor fibers in all anterior branches and three posterior extralaryngeal RLN branches. CONCLUSION: African American patients have a higher rate of RLN bifurcation compared to Caucasian patients but no statistically significant difference in distance from NEP. Female patients tend to have longer branching variants of bifid RLNs. RLN motor fibers reside primarily in the anterior branch but may occur in the posterior branch.