The Role of Continuous Positive Airway Pressure in Acute Bilateral Vocal Cord Paresis or Paralysis Post-Thyroidectomy.

OBJECTIVES: Acute post-thyroidectomy bilateral vocal cord paresis or paralysis (BVCP) is often managed with observation, botulinum toxin injection or tracheostomy. However, only a few cases discuss obstructive sleep apnea (OSA) in the context of BVCP with limited exploration of home sleep test (HST) and continuous positive airway pressure (CPAP) as post-operative assessment and management tools. This study suggests CPAP as a less invasive approach while awaiting vocal cord recovery. METHODS: A retrospective chart review was conducted on 2 female patients who presented with dyspnea and sleep-disordered breathing (SDB) symptoms post-thyroidectomy. Both patients underwent laryngoscopy and HSTs, followed by CPAP prescription. RESULTS: Case 1 (body mass index [BMI]: 32.6 kg/m2) and Case 2 (BMI: 20.1 kg/m2), aged 66 and 77 respectively, presented with post-surgery dyspnea and SDB symptoms. Laryngoscopy revealed left vocal cord paresis and right vocal cord paralysis in both cases. Although tracheostomy could provide definitive treatment, both cases were deferred for non-invasive options, which led to HST, confirming moderate OSA (PAT-derived apnea-hypopnea index (pAHI): 18/hour and 27.1/hour) leading to CPAP recommendation. In Case 2, 5 weeks of CPAP use resulted in dramatic improvements in her sleep quality, with continued benefits at 3-month follow-up. CONCLUSION: These cases underscore the value of considering sleep studies and CPAP as adjunctive tools in acute post-thyroidectomy BVCP management while awaiting vocal motion recovery. This report also further supports that BVCP sufficiently narrows the glottic airway, predisposing patients to OSA.

Optimizing the Diagnosis and Management of Pediatric Inducible Laryngeal Obstruction.

BACKGROUND: Pediatric inducible laryngeal obstruction (ILO) is difficult to diagnose and treat. Patients often undergo multiple specialist referrals, and long-term outcomes are not well reported. OBJECTIVES: To investigate the patterns of presentation, workup, and management of children who were diagnosed with ILO at the Stollery Children's Hospital. METHODS: Retrospective review with a prospective cohort of pediatric patients diagnosed with ILO from 2015 to 2023. We collected the demographic data, diagnostic tests, specialist referrals, time to diagnosis, symptom burden, associated comorbidities and aggravating factors, management, and treatment outcomes. A subset of patients was followed prospectively to determine treatment outcomes. A basic descriptive analysis was performed, and factors associated with time to resolution were studied. RESULTS: Seventy-eight patients met the criteria for inclusion, with 22 completing prospective questionnaires. The average age was 14 years old, and 75% were female. The majority required multiple specialist referrals. The majority were associated with exercise. Thirty-two (41%) patients had a presumed diagnosis of asthma, despite only four pulmonary function tests being consistent with asthma. Abortive breathing exercises were the most commonly employed (95%) and most successful (61%) nonsurgical management technique. Surgery was highly successful in a small cohort of patients. Median time to symptom resolution was 12 months, with 36% reporting symptoms persistent beyond 3 years. CONCLUSIONS: Pediatric ILO often goes undiagnosed for prolonged periods. Exercise-related symptoms are the most common. Management strategies have varied levels of success and a large proportion of patients have prolonged symptoms despite treatment, as supported by other recent evidence. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Bilateral Recurrent Laryngeal Nerve Injury Following Botulinum Toxin Injection at the Cricopharyngeus Muscle: Diagnosis, Anatomic Considerations, and ICU Management.

Bilateral vocal cord paralysis poses life-threatening risks to patients who do not undergo prompt diagnostic intervention and airway management. Although developing bilateral vocal cord paralysis is extremely rare, if injury does occur, it is more frequently due to surgical resection sequelae in the neck. This case is particularly unique as we present a patient with a history of stage III laryngeal carcinoma status post chemotherapy in remission, who developed respiratory distress three days following an upper endoscopy procedure for an esophageal stricture at the level of the cricopharyngeus muscle, where he received a botulinum injection. This manuscript discusses the anatomy, clinical practices of botulinum toxin, nerve innervation, and mechanisms of injury for patients who develop bilateral recurrent laryngeal nerve injury. In addition, this manuscript details vocal cord positioning and how the positioning of the cords during laryngoscopy investigation can lead to diagnostic confirmation. With few reported cases of bilateral recurrent laryngeal nerve injury secondary to botulinum toxin particularly at the cricopharyngeus level, this report should serve as a guide for future clinicians regarding the risks of using this toxin, the risks of local spread, and management.

Delayed-onset vocal cord palsy after thyroidectomy occurring despite normal initial post-operative endoscopy.

BACKGROUND: Recurrent laryngeal nerve (RLN) injury is a known complication of thyroidectomy. Most cases manifest immediately and are promptly recognized. Rarely, some patients experience delayed-onset vocal cord palsy. This can occur despite normal findings on intra-operative nerve monitoring and initial post-operative endoscopy. This can cause considerable distress for patients, and its incidence and prognosis should be recognized. METHODOLOGY: We report seven patients experiencing delayed-onset RLN palsy (RLNP) after thyroidectomy. All had normal findings on pre-operative flexible nasoendoscopy (FNE), intra-operative nerve monitoring at conclusion of surgery, and initial post-operative FNE. All diagnoses of RLNP were confirmed on endoscopy. Serial FNE examinations were performed to evaluate recovery. RESULTS: Of seven patients (43% male, median age 65 years), the median timing of delayed-onset RLNP was 12 (range 9-35) days. RLNP was diagnosed on the unilateral side of surgery in six out of seven patients (86%). All received conservative management, including referral to voice therapy. All seven patients recovered vocal cord function after a median duration of 24 weeks (range 8-52 weeks), and six within ~6 months (28 weeks). The incidence of this complication was 0.1% (among 6607 thyroidectomies). CONCLUSION: We report the first Australian series of delayed-onset vocal cord palsy after thyroidectomy. We explore its prognosis, discussing different pathophysiological mechanisms and the timeframe for recovery compared to most other RLN injuries. This may assist recognition of a rare complication, reassure patients, and facilitate early intervention to improve a patient's quality of life.

Approaching Saber-Sheath Trachea in a Patient with Bilateral Vocal Cord Abductor Palsy and Post Tracheostomy Tracheal Stenosis.

Human trachea has variable shapes and the most common are circular and oval-shaped. Other shapes are rare to find and usually related to some diseases. Such as the Saber-sheath shaped trachea, which was commonly attributed to patients with chronic obstructive pulmonary disease (COPD). This case is about a patient who was detected to have dual pathology, bilateral vocal cord abductor palsy, and post-tracheostomy complicated with tracheal stenosis for 40 years. Symptoms worsened in the last three years until he was admitted to the ward. However, upon managing this case with multilevel airway obstruction, we have found out that this patient who did not have COPD, has a Saber-sheath trachea shape. This finding may indicate that the shape is not limited to a certain disease only.

[The key problems of diagnosis and treatment of vocal cord paralysis].

Vocal cord paralysis is a common condition that significantly impairs laryngeal function and can even be life-threatening. Over nearly a century, researchers have conducted extensive animal and clinical studies to achieve accurate diagnosis and restore laryngeal function, making significant progress. Approaches have evolved from mechanically narrowing the glottis to restore phonation, to enlarging the glottis to relieve breathing difficulties, and ultimately to the development of surgical techniques aimed at restoring vocal cord mobility, significantly advancing the field. The publication of expert consensus guidelines on the diagnosis and treatment of vocal cord paralysis has standardized the principles and technical standards for managing this condition. However, a vast amount of related knowledge-including the disease's pathogenesis, diagnostic criteria, surgical principles, and techniques-still requires broader dissemination and further refinement. Advancing this knowledge will guide clinical practice and further enhance the diagnosis and treatment of this condition in China.

[Evaluation of the effect of endoscopic CO2laser arytenoidectomy on re-operation for failed posterior cordotomy].

Objective:To analyze the efficacy of endoscopic CO2 laser arytenoidectomy in treating bilateral vocal cord paralysis. Methods:Ninety-five patients who underwent endoscopic CO2 laser arytenoidectomy for bilateral vocal cord paralysis at the First Affiliated Hospital of Naval Medical University（Changhai Hospital） of Shanghai from January 2009 to December 2022 were included in this study. Among them, 59 patients underwent endoscopic CO2 laser arytenoidectomy as their first glottic enlargement surgery（Group A）, while 36 patients, who had previously undergone two unsuccessful CO2 laser-assisted posterior cordotomies, underwent endoscopic CO2 laser arytenoidectomy as a subsequent surgery（Group B）. Swallowing function, electronic laryngoscopy, perceptual voice evaluation, and objective voice analysis indicators were statistically analyzed before and after surgery to evaluate clinical efficacy. Results:The extubation rate after the first surgery was 84.75% in Group A and 86.11% in Group B, with total extubation rates of 94.92% and 94.44%, respectively. There were no significant differences between the two groups in preoperative and postoperative swallowing function, glottic size, or various voice evaluation indicators（P>0.05）. Within-group comparisons showed that postoperative swallowing function, glottic closure during phonation, perceptual evaluations of G（grade of hoarseness）, A（asthenia）, and B（breathiness） significantly worsened, with increased grades. The maximum transverse diameter of the posterior glottis during inspiration significantly increased, and the VHI-10 score was significantly higher postoperatively. Jitter, shimmer, and the harmonics-to-noise ratio significantly deteriorated, and maximum phonation time significantly shortened（P<0.05）. No significant differences were observed in postoperative R（roughness） and S（strain） compared to preoperative values（P>0.05）. Conclusion:Endoscopic CO2 laser arytenoidectomy can impair voice quality to some extent but effectively alleviates breathing difficulties in patients with bilateral vocal cord paralysis. For patients who did not achieve successful extubation with CO2 laser-assisted posterior cordotomy, endoscopic CO2laser arytenoidectomy is an effective reoperative method, ensuring a high extubation rate while preserving certain voice functions.

[A meta-analysis on the improvement of vocal function in unilateral vocal cord paralysis by reinnervation of the recurrent laryngeal nerve].

Objective:To conduct a systematic description and meta-analysis of the treatment of unilateral vocal cord paralysis（UVCP） with recurrent laryngeal nerve reinnervation through literature search, and to analyze the therapeutic effect of recurrent laryngeal nerve reinnervation on improving vocal function in UVCP. Methods:Electronic databases Pubmed, Web of Science, EMBASE, Cochrane Library, CNKI, and Wanfang databases were searched using relevant keywords and screened in strict accordance with the inclusion and exclusion criteria, and quality evaluations were conducted. Reported treatment outcomes were measured by relevant data extracted from literature, such as auditory perception assessment（GRBAS）, voice handicap index（VHI）, maximal phonation time（MPT）, jitter, shimmer, and noise harmonic ratio（NHR）, etc. Meta-analysis was performed by Revman5.3 and heterogeneity was analyzed using fixed effects or random effects models. Results:Eight articles were included in this study, all of which showed that the postoperative maximum phonation time of patients was significantly prolonged compared to preoperative, while the postoperative GRBAS score, Jitter, Shimmer, and NHR decreased compared to preoperative with statistical significance. Conclusion:The innervation of the internal laryngeal muscle was obtained through the reinnervation of the recurrent laryngeal nerve, which effectively improved the patient's vocal function and had a good long-term therapeutic effect. Although there was no difference in the efficacy of surgical methods for reconstructing the recurrent laryngeal nerve, the anastomosis between ansa cervicalis nerve and the recurrent laryngeal nerve is more ideal. Further randomized controlled studies with longer follow-up periods and larger samples will increase the credibility of their effectiveness.

[Efficacy analysis of ansa cervicalis anterior root-recurrent laryngeal nerve anastomosis in the treatment of unilateral vocal cord paralysis].

Objective:Investigates the application and clinical efficacy of ansa cervicalis anterior root-recurrent laryngeal nerve（RLN） anastomosis in the treatment of unilateral vocal fold paralysis（UVFP）. Methods:A prospective study was conducted with 92 UVFP patients admitted to our department from January 2018 to January 2022 who received ansa cervicalis anterior root-RLN anastomosis. The course of nerve injury ranged from 6 to 24 months. Videostroboscopy, voice subjective auditory perceptual assessment（GRBAS）, Voice Handicap Index（VHI-10）, voice objective acoustic analysis and laryngeal electromyography（EMG） were used to evaluate the efficacy of the operation. Results:Videostroboscopy showed that although the movement of vocal cords did not return to normal 12 months after operation, their volume and muscle tension were significantly improved and their positions were adducted to the median or near-median. Also the glottic closure, vocal cord position, vocal cord edge, symmetry and regularity of vocal cord vibration were significantly improved than pre-operation（P<0.01）. The five indexes of GRBAS（Grade, Roughness, Breathiness, Asthenia, Strain） and VHI-10, as well as voice acoustic parameters（Jitter, Shimmer, NHR） post-operation were significantly reduced, while the maximum phonation time（MPT） was significantly longer（P<0.01）. The results of laryngeal EMG indicated that the maximum voluntary motor unit recruitment（VMUR） post-operation was significantly recovered（P<0.01）, which confirmed that the affected laryngeal muscle obtained effective nerve reinnervation. Conclusion:Ansa cervicalis anterior root-RLN anastomosis can effectively improve the voice function of patients which is safe and satisfactory. It is an ideal method for the treatment of unilateral RLN injury.

[The current status and development of nerve repair techniques for bilateral vocal cord paralysis].

The related research of nerve repair for bilateral vocal cord paralysis（BVCP） can be traced back to a century ago. There is still no standardized surgical therapeutic schedule and the evaluation of curative effect, due to the variability and complexity of laryngeal nerve innervation. Otolaryngologists have been constantly weighing and improving the surgical plan in relieving airway obstruction, maintaining vocal function and reducing cough to protect the normal physiological function of the larynx. Different medical institutions have great differences in the treatment methods. Many studies and literatures were published on the treatment of BVCP, yet have few related works on the application of it's nerve repair technology presently. The research progress of nerve repair technology for BVCP were described, along with its developing trend, aiming to lay the foundation for the future technical exploration and development.

Clinical and neurophysiological characterization of p.Gly95Ser mutation in DCTN1: a study in a Thai family and a brief review.

INTRODUCTION: Mutations in the Dynactin 1 (DCTN1) gene lead to various neurodegenerative disorders. The p.Gly59Ser mutation, the first pathogenic mutation identified in DCTN1, was initially reported in a family with distal hereditary motor neuropathy and early vocal cord paralysis. Since its discovery in 2003, this mutation has been documented in only three families worldwide, to the best of our knowledge. METHODS: This study examines six patients from a Thai family carrying the p.Gly59Ser mutation in DCTN1 and includes a literature review. RESULTS: Five of the patients were female. The mean age of onset was 32.6 ± 1.9 years. Thai patients showed early involvement of intrinsic hand, facial, and bulbar muscles, with vocal cord impairment manifesting later in the disease course. Tongue fasciculations, not previously reported with this mutation, were observed in most Thai patients. Bilateral split-hands were consistently noted. Arytenoidectomy and cordotomy have proven beneficial in relieving upper airway obstruction and preventing life-threatening upper airway complications from vocal cord paralysis. CONCLUSIONS: The p.Gly59Ser mutation in DCTN1 presents with autosomal-dominant, adult-onset, lower motor neuronopathy/neuropathy. Compared to earlier reports, Thai patients exhibited more widespread involvement, including facial, bulbar, tongue, vocal cord, and limb muscles. In addition to vocal cord paralysis, the split-hand phenomenon emerges as another clinical hallmark of this condition.

Delayed Onset Bilateral Vocal Cord Palsy in Miller Fisher Syndrome: The Rehabilitation Outcome.

Miller Fisher syndrome (MFS) typically presents with acute development of ataxia, ophthalmoplegia, and areflexia. Bilateral vocal cord palsy (BVCP) is a rare manifestation of MFS. We present a case of a 66-year-old male diagnosed with MFS complicated by an unusually delayed onset of BVCP while undergoing inpatient rehabilitation. We also describe the inpatient rehabilitation course, including the use of a patient-guided suspension system (PGSS) as a therapeutic adjunct to aid gait training, resulting in significant functional improvement in ambulation and activities of daily living. Given the rarity of BVCP in MFS, this case highlights the importance of healthcare professionals being aware of this phenomenon so that prompt treatment can be initiated to reduce significant morbidity. Innovative treatment approaches such as the use of a PGSS may also prove beneficial in the rehabilitation of patients with MFS with significant ataxia.

Unilateral Vocal Cord Paralysis in a Patient with Anti-Galactocerebroside Antibodies: A Case Report.

Anti-galactocerebroside (Gal-C) antibodies are present in patients with conditions such as Guillain-Barré syndrome and mycoplasma pneumonia. We report a rare case of left vocal cord paralysis in a patient with anti-Gal-C IgG antibodies that improved after administeration of antivirals and steroids.

Additional injection laryngoplasty as a salvage treatment for unilateral vocal fold paralysis.

OBJECTIVES: Injection laryngoplasty (IL) has been widely used as an initial treatment option for unilateral vocal fold paralysis (UVFP). An additional (second) IL is considered a salvage treatment for unsatisfactory outcomes of initial IL resulting from inadequate injection or early resorption of the injection material. This study aims to evaluate the efficacy of additional IL, distinguishing between "salvage" (within 4 months) and "repeated" injections (beyond 4 months), and to analyze prognostic factors for successful outcomes. METHODS: This retrospective study involved patients who received IL at Asan Medical Center from January 2014 to December 2020. Voice parameters were collected after each procedure, and those who conducted the statistical analysis were blinded to the study subjects. Among the 65 patients who underwent additional IL, 51 patients were enrolled in this study. Postinjection grade, roughness, breathiness, asthenia, strain (GRBAS) scales were used to determine satisfactory treatment outcomes. Success of the additional IL was defined as a postinjection grade of dysphonia score of 0 or 1, with a reduction in grade compared with the preinjection grade. RESULTS: The mean age of the patients was 61.6 years. Out of a total of 51 patients, 37 were men participating in the study. The odds ratio represents the likelihood of success in the second IL. Improved voice outcome after the additional IL was maintained in 23 (45%) patients. Compared with the failure group, the success group had a longer injection time interval between the initial and additional injection (9.1 vs. 7.4 months, respectively, p = 0.010). The success group had a higher proportion of patients with injection intervals >6 months (73.9% vs. 42.9%, p = 0.026). Logistic regression analysis revealed an injection interval >6 months had an odds ratio of 0.265 (confidence interval: 0.080-0.874, p = 0.029). CONCLUSIONS: Additional injections would benefit the patients whose voice outcomes are maintained for a longer period (>6 months) after the first injection.

Long-Term Outcomes of Recurrent Laryngeal Nerve Repair/Reconstruction in Oncological Settings.

Vocal cord paralysis results from involvement of the recurrent laryngeal nerve (RLN), either before the surgery or following excision. Coaptation of the resected edges utilising microsurgical techniques is the most promising therapeutic strategy available for RLN excision. The RLN can be repaired by direct epineural coaptation or using nerve grafts adhering to recommended microsurgical techniques. This article aims to convey our experience with RLN resections/injuries and their subsequent effects. We assessed the RLN repairs that our institute had completed from April 2018 to September 2023(5 years and 5 months) including follow-up of minimum 1 year. The Functional Oral Intake Scale (FOSI) was applied to assess dysphagia, aspiration risk, and glottic gap by laryngoscopy, and GRBAS (Grade, Roughness, Breathiness, Asthenia, Strain) comprised the basis for the assessment of voice quality by speech specialists. Surgical technique included using 9-0 Ethilon either for primary repair or for repair with a nerve graft. Ten patients were included in the study; six (60%) of them were male with the median age of 32 years. At 12-month follow-up, only 10% (n = 1) was found to have dysphagia. Only 10% (n = 1) had a mild harsh voice. This same patient was the only patient to show a minimal remnant glottic gap. Ten percent (n = 1) patient showed B/l cord mobility at 12 months, while 30% (n = 3) showed flickering movements of the affected vocal cord. In all the patients, the opposite vocal cord was found to be compensating. Thus, immediate repair of RLN is helpful along with the general physiological adaptation of vocal cords to improve phonation and reduce aspiration and dysphagia risks, thus helping to improve the quality of life. The right procedure should choose from the armoury after careful intraoperative assessment.

An Overview of Laryngologic Manifestations of Neurologic Diseases.

PURPOSE OF REVIEW: Patients with various neurological disorders often present with or manifest during their disease process laryngologic pathology that can lead to significant morbidity. Recognizing and treating this aspect of their disease may be crucial in optimizing patient outcome. RECENT FINDINGS: We discuss updated information and management regarding various neurological disorders that affect the larynx and how these sequelae are diagnosed and treated. An understanding of the laryngologic manifestations of neurological disorders will facilitate management of these patient populations. Preventing and minimizing complications arising from these sequelae will improve quality of life and optimize patient outcomes.

A Patient With Unilateral Vocal Cord Paralysis Presenting to the Emergency Department With Voice Changes and Dyspnea.

Unilateral vocal cord paralysis can cause a change in phonation and dyspnea and can be a cause of distress for a patient. The causes are varied and include post-surgical and post-intubation causes, malignancy, and other etiologies. Here, we present the case of a 72-year-old female who presented to the ED with a new onset of a "raspy voice" and dyspnea and had undergone an L4-L5 laminectomy with associated endotracheal intubation two weeks prior to ED presentation. Because of the complaint of a change in her voice, a nasopharyngolaryngoscopy (NPL) was performed, which demonstrated left-sided unilateral vocal cord paralysis. The patient was admitted to the hospital and was evaluated by neurology, pulmonology, and otolaryngology services. The discharge diagnosis was unilateral vocal cord paralysis, most likely caused by the patient's recent intubation. This case demonstrates the value of an NPL in the ED as part of the evaluation of a patient with dyspnea and a change in phonation.

Paediatric Laryngeal Ultrasound: A Retrospective Cohort Study in Aotearoa New Zealand and an International Survey.

OBJECTIVE: Vocal fold immobility (VFI) is a cause of significant morbidity and mortality in the paediatric population. Laryngoscopy is the current first-line investigation for patients with suspected VFI. Laryngeal ultrasound (LUS) has recently emerged as an alternative method of identifying VFI. Compared to laryngoscopy, LUS is less invasive, does not require anaesthesia, and can be performed by non-otolaryngologists. The objectives of this study are to evaluate LUS as a diagnostic method for the identification of VFI in a cohort of paediatric patients in Aotearoa New Zealand (NZ) and to estimate the frequency of use of LUS in the paediatric population by clinicians around the world. METHODS: A retrospective, single-centre cohort study was performed on all paediatric patients who had undergone laryngoscopy and LUS at Starship Children's Health in Auckland, NZ, between 2020 and 2023. An eight-question survey was also developed and distributed to better understand clinicians' use of LUS in their clinical practice to diagnose paediatric VFI globally. RESULTS: Twenty-nine paediatric patients met the inclusion criteria. LUS demonstrated good sensitivity (80.95%) for detecting VFI and increased to 93.33% for the detection of unilateral VFI. Of the 87 respondents to the survey, 41.38% utilise LUS in their clinical practice in the paediatric population. The main barriers to implementation of LUS as identified by non-users were lack of equipment, expertise, and training. CONCLUSIONS: These findings support the use of LUS as an accurate diagnostic tool for the detection of unilateral VFI. Further studies in non-surgical populations and in patients with bilateral VFI, as well as standardised guidelines for LUS technique and reporting, are required.

Effective Treatments for Abductor Vocal Cord Paralysis: A Comprehensive Review.

Abductor vocal cord paralysis (AVCP) is a disabling disorder that affects the voice and the quality of life of a patient, and hence, there is importance in providing a detailed knowledge of its aetiology and management. In this review article, we offer an implicational definition of AVCP and a discussion of its background, viewed as potentially affecting voice production and health. Finally, we explore modalities of diagnosis by medical history and physical examination, visualization techniques like laryngoscopy and stroboscopy, and radiographic imaging such as computed tomography (CT) and magnetic resonance imaging (MRI) scans. The article reviews and categorizes approaches into operative and non-operative treatments, including injection laryngoplasty, voice therapy, botulinum toxin injections, and the management of Reinke's edema. Surgical approaches, like arytenoid adduction, cordotomy, and posterior cordotomy, are also scrutinized taking their indication, efficacy, and complication profile into consideration. Learning about the advantages and drawbacks of the following experimental yet promising directions like nerve-muscle pedicle implantation, nerve reinnervation, and engineering of tissues is therefore highly necessitated. In conclusion, the review details the measures that have shown to be useful in the treatment process and their impact on the future practice of clinical work, calling for a more clarified structure of the organization of diagnostic, therapeutic, and rehabilitative activities. Future research directions are outlined based on the gaps which include the development of new treatment approaches, the evaluation of treatment for long-term effects, and the need for interdisciplinary cooperation in the medical field for the benefit of the patients.