Prospective Evaluation of the Efficacy of Isolated Balloon Eustachian Tuboplasty: Short- and Medium-term Follow-up Results Based on Tubomanometry, ETDQ-7, Tympanometry, and Valsalva Maneuver.

Introduction Balloon eustachian tuboplasty (BET) allows the treatment of the main etiology of eustachian tube disfunction (ETD). Objective To evaluate the efficacy of isolated BET, through objective and subjective results, in the short and medium term, in patients with chronic obstructive ETD. Methods Adult patients diagnosed with chronic obstructive ETD who underwent BET between January 2018 and December 2020 were enrolled in the study. We performed a prospective observational study of BET efficacy, by comparing subjective data, based on the Eustachian Tube Dysfunction Questionnaire-7 (ETDQ-7), and objective data, obtained by tympanometry, objective Valsalva maneuver and tubomanometry, prior to BET with these outcome tools on postprocedure follow-up. Results In total, 30 BETs were performed and analyzed. There were no complications with the procedure. Analysis of BET efficacy was performed in the short-term (average of 7.5 weeks) and in the medium-term (average of 8 months). There was a significant reduction ( p < 0.0001) in the total ETDQ-7 score from baseline to both follow-up periods. A normalization of the ETDQ-7 score was observed in 60 and 83.3% of the performed procedures, in the short- and medium-term, respectively. In tubomanometry, we verified a significant improvement ( p < 0.0001) at all pressures, with a normalization of tubomanometry values in 53.3% and 43.3% of cases in the short- and medium-term, respectively. Tympanogram normalization occurred in 71.4% of patients with abnormal preoperative assessments. Conclusion As an isolated procedure, BET results in significant improvements in symptomatology and objective metric results. This, associated with its safety profile, currently makes BET the most indicated therapeutic option in refractory obstructive ETD.

Functional and patient-reported outcomes of bone-anchored hearing aids (BAHA): A prospective case series study.

Objective: The purpose of this study was to evaluate the functional and patient-reported outcomes, and their correlation, after percutaneous bone-anchored hearing aid (BAHA) implantation. Methods: A prospective study was conducted between January 2018 and December 2020 in a tertiary care center. All adult patients who were implanted with a percutaneous BAHA device during this evaluation period were included in the study. Complete auditory function and patients reported outcome measures (PROMs) were assessed in the preoperative period and 6 months after the implant activation. The PROMs included a generic form (Medical Outcome Study 36 Short Form Healthy Survey (MOS SF-36)), and three disease-specific forms (Hearing Handicap Inventory (HHI), Satisfaction with Amplification in Daily Life Scale (SADLS), and Tinnitus Handicap Inventory (THI)). Results: Twenty-two patients with an average age of 53 years were included in the study. The overall functional gain with the BAHA in sound-field pure tone average (PTA) was 29 dB, with no statistically significant differences according to surgical indication (F(3,18) = 2.319, p = 0.110). The greater the preoperative air-bone gap, the greater the functional gain obtained (r = 0.505, p < 0.05). In the PROMs, we found a significant improvement in HHI scores (p < 0.005) and a significant increase in overall SADLS scores (p < 0.05) with the use of percutaneous BAHA devices. We did not verify any statistically significant correlation between functional and PROMs results. Conclusions: The BAHA is a safe and effective alternative hearing rehabilitation option in selected patients. The PROMs results prove patient's overall satisfaction.

The intriguing nature of dorsal root ganglion neurons: Linking structure with polarity and function.

Dorsal root ganglion (DRG) neurons are the first neurons of the sensory pathway. They are activated by a variety of sensory stimuli that are then transmitted to the central nervous system. An important feature of DRG neurons is their unique morphology where a single process -the stem axon- bifurcates into a peripheral and a central axonal branch, with different functions and cellular properties. Distinctive structural aspects of the two DRG neuron branches may have important implications for their function in health and disease. However, the link between DRG axonal branch structure, polarity and function has been largely neglected in the field, and relevant information is rather scattered across the literature. In particular, ultrastructural differences between the two axonal branches are likely to account for the higher transport and regenerative ability of the peripheral DRG neuron axon when compared to the central one. Nevertheless, the cell intrinsic factors contributing to this central-peripheral asymmetry are still unknown. Here we critically review the factors that may underlie the functional asymmetry between the peripheral and central DRG axonal branches. Also, we discuss the hypothesis that DRG neurons may assemble a structure resembling the axon initial segment that may be responsible, at least in part, for their polarity and electrophysiological features. Ultimately, we suggest that the clarification of the axonal ultrastructure of DRG neurons using state-of-the-art techniques will be crucial to understand the physiology of this peculiar cell type.

Regenerative medicine for the treatment of spinal cord injury: more than just promises?

Spinal cord injury triggers a complex set of events that lead to tissue healing without the restoration of normal function due to the poor regenerative capacity of the spinal cord. Nevertheless, current knowledge about the intrinsic regenerative ability of central nervous system axons, when in a supportive environment, has made the prospect of treating spinal cord injury a reality. Among the range of strategies under investigation, cell-based therapies offer the most promising results, due to the multifactorial roles that these cells can fulfil. However, the best cell source is still a matter of debate, as are clinical issues that include the optimal cell dose as well as the timing and route of administration. In this context, the role of biomaterials is gaining importance. These can not only act as vehicles for the administered cells but also, in the case of chronic lesions, can be used to fill the permanent cyst, thus creating a more favourable and conducive environment for axonal regeneration in addition to serving as local delivery systems of therapeutic agents to improve the regenerative milieu. Some of the candidate molecules for the future are discussed in view of the knowledge derived from studying the mechanisms that facilitate the intrinsic regenerative capacity of central nervous system neurons. The future challenge for the multidisciplinary teams working in the field is to translate the knowledge acquired in basic research into effective combinatorial therapies to be applied in the clinic.

Chapter 17: Transthyretin: an enhancer of nerve regeneration.

Transthyretin (TTR), a plasma and cerebrospinal fluid protein secreted by the liver and choroid plexus, is mainly known as the physiological carrier of thyroxine (T(4)) and retinol. Under pathological conditions, various TTR mutations are related to familial amyloid polyneuropathy (FAP), a neurodegenerative disorder characterized by deposition of TTR amyloid fibrils, particularly in the peripheral nervous system (PNS), leading to axonal loss and neuronal death. Recently, a number of TTR functions in neurobiology have been described; these may explain the preferential TTR deposition, when mutated, in the PNS of FAP patients. In this respect, and with a particular relevance in the PNS, TTR has been shown to have the ability to enhance neurite outgrowth in vitro and nerve regeneration following injury, in vivo. In the following pages, this novel TTR function, as well as its importance in nerve biology and repair will be discussed.

Transthyretin internalization by sensory neurons is megalin mediated and necessary for its neuritogenic activity.

Mutated transthyretin (TTR) causes familial amyloid polyneuropathy, a neurodegenerative disorder characterized by TTR deposition in the peripheral nervous system (PNS). The origin/reason for TTR deposition in the nerve is unknown. Here we demonstrate that both endogenous mouse TTR and TTR injected intravenously have access to the mouse sciatic nerve. We previously determined that in the absence of TTR, both neurite outgrowth in vitro and nerve regeneration in vivo were impaired. Reinforcing this finding, we now show that local TTR delivery to the crushed sciatic nerve rescues the regeneration phenotype of TTR knock-out (KO) mice. As the absence of TTR was unrelated to neuronal survival, we further evaluated the Schwann cell and inflammatory response to injury, as well as axonal retrograde transport, in the presence/absence of TTR. Only retrograde transport was impaired in TTR KO mice which, in addition to the neurite outgrowth impairment, might account for the decreased regeneration in this strain. Moreover, we show that in vitro, in dorsal root ganglia neurons, clathrin-dependent megalin-mediated TTR internalization is needed for TTR neuritogenic activity. Supporting this observation, we demonstrate that in vivo, decreased levels of megalin lead to decreased nerve regeneration and that megalin's action as a regeneration enhancer is dependent on TTR. In conclusion, our work unravels the mechanism of TTR action during nerve regeneration. Additionally, TTR presence in the nerve, as is here shown, may underlie its preferential deposition in the PNS of familial amyloid polyneuropathy patients.